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Varela, E.L.P.;  Gomes, A.R.Q.;  Santos, A.D.S.B.D.;  Carvalho, E.P.D.;  Vale, V.V.;  Percário, S. Antioxidant Effects of Lycopene. Encyclopedia. Available online: https://encyclopedia.pub/entry/39875 (accessed on 02 July 2024).
Varela ELP,  Gomes ARQ,  Santos ADSBD,  Carvalho EPD,  Vale VV,  Percário S. Antioxidant Effects of Lycopene. Encyclopedia. Available at: https://encyclopedia.pub/entry/39875. Accessed July 02, 2024.
Varela, Everton Luiz Pompeu, Antônio Rafael Quadros Gomes, Aline Da Silva Barbosa Dos Santos, Eliete Pereira De Carvalho, Valdicley Vieira Vale, Sandro Percário. "Antioxidant Effects of Lycopene" Encyclopedia, https://encyclopedia.pub/entry/39875 (accessed July 02, 2024).
Varela, E.L.P.,  Gomes, A.R.Q.,  Santos, A.D.S.B.D.,  Carvalho, E.P.D.,  Vale, V.V., & Percário, S. (2023, January 08). Antioxidant Effects of Lycopene. In Encyclopedia. https://encyclopedia.pub/entry/39875
Varela, Everton Luiz Pompeu, et al. "Antioxidant Effects of Lycopene." Encyclopedia. Web. 08 January, 2023.
Antioxidant Effects of Lycopene
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This entry is adapted from the peer-reviewed paper 10.3390/nu14245303

Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. 

lycopene malaria oxidative stress carotenoids supplementation antioxidants adjuvant treatment

1. Introduction

Malaria is currently endemic in 85 countries and is found on most continents, but it is mostly confined to tropical and subtropical regions. It is noteworthy that repeated Plasmodium infection does not result in complete immunity, so populations in endemic regions are continuously susceptible to infection, transmission, morbidity, and mortality. Moreover, the lack of effective prevention strategies, including medications and/or vaccines, contributes significantly to this scenario. In 2020, there were 241 million cases, and 627,000 people died worldwide from the disease [1]. Almost all malaria-related deaths result from Plasmodium falciparum infection.
The pathophysiological mechanisms involved in the disease are complex and multifactorial. Inflammatory molecules are greatly involved and related to several cell signaling pathways. Indeed, after Plasmodium infection, an inflammatory reaction may be observed, with a predominance of neutrophils, lymphocytes, and monocytes, which are attracted by the presence of the parasite in the body [2][3][4]. Furthermore, leukocytes induce the expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-6, IL-17, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), that play an important role in the protection against malaria and elimination of parasites, by inducing monocyte phagocytosis, favoring the elimination of parasitized erythrocytes and limiting the progression of uncomplicated malaria to malaria with serious complications [5][6][7].
Additionally, in the recovery phase, regulatory cytokines, including IL-4, IL-10, chemokines, including IL-8, macrophage inflammatory protein (MIP)-1α, MIP-1β, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) [8][9][10][11] and transforming growth factor-β, neutralize the pro-inflammatory response by inhibiting the production of T helper 1 cytokines, contributing to the elimination of the parasite and reducing the risk of serious clinical complications [12][13][14].
However, a disturbance in the balance of pro- and anti-inflammatory cytokines and the underlying inflammatory process has been implicated in the pathogenesis of cerebral malaria and is associated with disease severity and death [11][15][16]. Such disturbance may be promoted by oxidative stress, which is known to intensify inflammation through tissue destruction and the release of danger signals by necrotic cells [17][18]. According to Ty et al. [19], reactive oxygen and nitrogen species (RONS) play an important role in triggering inflammation in malaria since these are produced in excess during infection and are potent inducers of inflammatory cytokines, suggesting the important role of oxidative stress in the pathophysiology of the disease [19][20][21].
Given the tropism of Plasmodium species for tissues such as blood [22], important systemic effects, including the induction of cytokines and RONS, which are closely associated with anemia, paroxysms, cerebral malaria, among other symptoms of systemic infection, are marked during the disease [20][23][24][25].
The oxidative changes occurring during infection that led to oxidative stress are a result of several different mechanisms, including the degradation of hemoglobin by the malaria parasite, producing redox-active by-products, such as free heme and hydrogen peroxide (H2O2) [26]. These radicals stimulate a series of oxidative reactions, leading to a decrease in the antioxidant defense system, through the consumption of micronutrients, including vitamin A, zinc, ascorbic acid (vitamin C), α-tocopherol (vitamin E), and carotenoids, among others [27]. In fact, in malaria-endemic areas, P. falciparum-infected individuals present lower plasma concentrations of various micronutrients compared to healthy individuals [28].
On the other hand, these micronutrients play essential roles in the antioxidant system and are implicated in resistance to malaria infection [29]. In this sense, it has been shown that vitamin A, zinc, and selenium can interfere with the progression of oxidative reactions during malaria in mice infected with P. berghei [30]. Additionally, studies have suggested that the periodic supplementation of vitamin A and zinc can reduce the incidence of febrile episodes and parasitemia, being an effective and low-cost strategy to decrease P. falciparum morbidity in preschool children [31][32].
Other studies also support the hypothesis that the use of carotenoids by the host increases during malaria, suggesting that the nutritional status is an important modulating factor in the disease [28][33]. In this regard, it has been suggested that increased plasma lycopene concentration is associated with faster resolution of parasitemia in children infected with P. falciparum, being effective in maintaining the oxidative balance [34].

2. Oxidative Stress

Oxidative stress occurs when RONS overwhelm cellular defenses, causing damage to proteins, membranes, and deoxyribonucleic acid (DNA) [35]. It is the result of a disturbance in the balance between RONS and antioxidants in favor of RONS [36]. Under physiological conditions, endogenous RONS are generated by enzymatic systems, including nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and nitric oxide synthase (NOS), as a by-product of mitochondrial electron transport chain reactions (Figure 1) or by metal-catalyzed oxidation [37][38].
Figure 1. Production of reactive oxygen species from the transfer of electrons from the electron transport chain.
In this regard, the free radical superoxide (O2•−), resulting from the monoelectronic reduction of oxygen, is considered the main precursor of other RONS since, after its formation, it can react with other molecules giving rise to other free radicals, such as hydroxyl (OH•), alkoxyl (RO-), and peroxyl (ROO-), in addition to other molecules that do not meet the definition of free radicals, but take part of oxidative reactions in a meaningful way, such as H2O2. Nitric oxide (NO) is among the molecules that can react with O2•−, and the reaction between them generates the free radical peroxynitrite (ONOO-). Additionally, O2•− can be unmuted to form H2O2, and it can be broken down through Fenton or Haber-Weiss reactions, leading to the generation of OH• [39][40].
These RONS-generating chain reactions are initially controlled by antioxidant defense systems that act quickly, neutralizing any molecule that can potentially develop into a RONS or any free radical with the ability to induce the production of other pro-oxidants [41]. Three enzymes are critical in this process, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). These enzymes, respectively, unmute O2•− and break down H2O2 or hydroperoxides (ROOH) into harmless molecules such as H2O, alcohol, and oxygen (O2) [42]. The class of endogenous antioxidants also includes glutathione reductase, and reduced glutathione (GSH), in addition to small molecules such as coenzyme Q and uric acid (UA), among others [43]. Since they can be synthesized by the body in response to oxidative aggression, the researchers nominate endogenous antioxidants as mobilizable antioxidant molecules.
However, in diseases in which oxidative stress is a pathogenic mediator, including cancer and malaria, mobilizable antioxidants are not sufficient to maintain cell homeostasis due to the decreased synthesis of antioxidant enzymes and increased use of these antioxidants, among other factors [44][45][46].
In these cases, supplementation with dietary antioxidants is essential to maintain optimal cell function. Vitamins, including vitamins E and C, phenolic substances, such as flavonoids, resveratrol, and carotenoids, including β-carotene and lycopene, and drugs, such as N-acetylcysteine (NAC), among others, belong to this category [47][48]. Dietary antioxidants neutralize or eliminate RONS by binding or donating electrons to pro-oxidants, and in the process, they become free radicals but with less harmful effects. These “new radicals” are more easily neutralized and rendered completely harmless by other antioxidants in this group [49]. Thus, this class of antioxidant molecules can also be referred to as consumable antioxidants, as they are consumed in the face of oxidative aggression. Thus, consumable and mobilizable antioxidants act synergistically to fight the excessive increase in RONS, which can be a primary cause or a secondary complication of various diseases [50][51], as in malaria [52][53].

3. Oxidative Stress in Malaria

In malaria, oxidative stress is caused by four main mechanisms: a host defense against Plasmodium infection; ischemia-reperfusion syndrome; direct production of oxidative species by the parasite; and the metabolism of antimalarial drugs [54].

3.1. Oxidative Stress as a Host Defense Mechanism

RONS are essential for several physiological functions of the body, including cell survival, growth, proliferation, and differentiation, as well as the immune response [55][56].
As for the immune response, RONS are important for phagocytes, including neutrophils and monocytes/macrophages, which are highly activated during malaria, helping these cells phagocytize and destruct parasites [57][58].
In this sense, the body’s defense system responds to infection by primarily recruiting neutrophils [59]. When neutrophils engulf the parasites, they induce a respiratory burst (Figure 2), in which O2 enzymatically reacts with NADPH oxidase present in the plasma and the phagosomal membrane of neutrophils, forming O2•− [4]. O2•− and its derivatives H2O2 and OH•, when released by activated neutrophils in the phagosome, are essential to kill ingested pathogens [60].
Figure 2. Oxidative stress as a host defense mechanism in response to infection by Plasmodium sp.
In addition, activated neutrophils produce cytokines, such as GM-CSF and M-CSF, and chemokines, including MIP-1α and MIP-1β, which attract these cells and are essential for monocyte mobilization [61]. These leukocytes engulf and kill the parasites through the oxidative action of O2•−, which is generated in the same way as in neutrophils, as well as by the action of NO, which is produced by the macrophage from the reaction of NOS with L-arginine [62][63]. Additionally, the NO and O2•− generated react to form other RONS, such as ONOO-, intensifying the cytotoxicity directed against the parasites [64].
Furthermore, neutrophil and macrophage myeloperoxidase is activated and uses H2O2 as a substrate to produce hypochlorous acid, a highly bactericidal compound [65][66]. On the other hand, phagocytosis and the consequent action of RONS, including O2•− and NO, as well as other toxic products, can exacerbate the condition due to rupture of the parasitized erythrocytes, during which normal uninfected erythrocytes can also be destroyed, stimulating cytoadherence and, consequently, potentially blocking blood flow, causing ischemia and anemia [67][68].

3.2. Oxidative Stress Due to Ischemia-Reperfusion Syndrome

In individuals with malaria, severe anemia induces microvascular dysfunction, leading to recurrent episodes of initial restriction of blood supply to organs, which can lead to ischemia and nutrient and oxygen deprivation, followed by subsequent restoration of concurrent perfusion and reoxygenation [54][69]. This process is called ischemia-reperfusion syndrome and can occur in malaria due to the sequestration of parasitized erythrocytes, as a result of the destruction of erythrocytes caused by the parasites and RONS during the paroxysm of malaria, and due to cytoadherence of erythrocytes to blood vessels [70].
Furthermore, this syndrome can trigger anaerobic metabolism, the production of lactic acid, and the consequent depletion of adenosine triphosphate (ATP). As ATP availability is reduced, ATP-dependent ion channels begin to fail. At the same time, calcium overload and excessive RONS production open the mitochondrial permeability transition pore, further reducing ATP levels [71][72]. During the ischemic process, the degradation of ATP causes the accumulation of xanthine oxidase (XO) and hypoxanthine due to the lack of oxygen. When the blood supply is resumed, XO acts on hypoxanthine resulting in the production of O2•− (Figure 3), which can later be converted into OH• in the presence of transition metals and, consequently, trigger oxidative stress [73][74].
Figure 3. Oxidative stress due to ischemia-reperfusion syndrome during malaria.
During this process, UA is also formed, which is a weak organic acid present mainly as monosodium urate at physiological pH [75]. UA can be found in the host organism during malarial infection and can act by eliminating RONS and chelating transition metal ions or even by reducing NOS expression, impairing NO release [76][77]. Previous studies have shown that plasma UA levels in P. falciparum-infected children increase during acute episodes and with disease severity, suggesting that UA is an important mediator in the pathophysiology of malaria [78][79].
In the ischemia-reperfusion syndrome, RONS can be produced during ischemia but is massively increased during reperfusion, amplifying and propagating oxidative damage and destroying the integrity of proteins, membranes, and microvascular endothelium [80].

3.3. Oxidative Stress Due to the Metabolism of the Parasite

Another important oxidative mechanism in malaria is mainly triggered by the metabolism of the parasite, as well as by the potentially oxidative by-products generated and released from red blood cells destroyed by the action of the parasite [81]. Inside the erythrocyte, the parasite digests hemoglobin in its acidic digestive vacuole, forming essential amino acids for parasite development and proliferation [82]. However, in this process, ferroprotoporphyrin IX or heme complex (FPIX) is released, which is toxic to the parasite. On the other hand, this complex can still be detoxified within the parasite by polymerization [83].
Although the parasite manages to polymerize FPIX, resulting in a nontoxic derivative, hemozoin, also known as a malarial pigment, a significant amount escapes polymerization [84]. Thus, the ferrous iron (Fe2+) from FPIX is oxidized to the ferric state (Fe3+), with the consequent production of superoxide, which dismutates to H2O2 (Figure 4). This oxidative reaction chain leads to the production of OH• from reactions involving H2O2 and Fe3+, such as the Fenton and Haber–Weiss reactions [85].
Figure 4. Oxidative stress as a consequence of parasite metabolism.
These free radicals can cause damage to the parasite’s digestive vacuole membrane, eventually killing it [81]. However, the rapid development and proliferation of the parasite, associated with the RONS generated and released inside the erythrocytes, cause structural damage to the erythrocytes [86]. This results in increased membrane permeability for ions, increased cell volume, oxidation of sulfhydryl groups, and reduced deformability, contributing to the loss of erythrocyte function and cell lysis [67][87].
Consequently, all intra-erythrocyte content, including RONS, will be released to the extracellular environment, resulting in damage to several biomolecules, such as lipids, proteins, and DNA, as well as enzyme inactivation, apoptosis induction, modification of surface adhesion molecule expression of leukocytes and endothelial cells, and alteration in the bioavailability of NO, compromising homeostasis and, ultimately, its survival [88][89]. These changes expose the host organism to a highly oxidative environment (Figure 5), implying the development of systemic complications such as reduced blood flow and severe anemia and also facilitating the entry of parasites into tissues such as the lung and brain, which can lead to organ failure [83][90][91][92].
Figure 5. Consequences of the multiplication of parasites in the erythrocyte.

3.4. Oxidative Stress as a Consequence of the Metabolization of Antimalarial Drugs

The drug treatment of malaria is specially designed to interrupt parasite proliferation, responsible for the pathogenesis and clinical manifestations of the infection, to destroy the latent forms of the parasite (hypnozoites) to prevent late relapses, and to prevent the transmission of the parasite, through the use of drugs that prevent the development of sexual forms of the parasites [93][94].
In this context, one of the main targets of antimalarial drugs is the intracellular pathway of heme metabolism, which is implicated in the production of RONS and the consequent death of the parasite [95][96]. Therefore, chloroquine, a quinoline blood schizonticidal drug used to treat severe and uncomplicated cases of malaria, can act by preventing FPIX polymerization, causing the accumulation of FPIX in the parasite’s digestive vacuole and consequent lethal oxidative stress in the parasite [97][98][99]. However, there are increasing reports of P. falciparum resistance to quinoline antimalarials, highlighting the importance of the P. falciparum chloroquine resistance transporter, a member of the drug/metabolite transporter superfamily located in the parasite’s digestive vacuole, as the main responsible for chloroquine resistance [100][101][102].
Other studies indicate that, in addition to showing chemical similarity with chloroquine and a similar mechanism of action, other quinolines, such as quinine, amodiaquine, lumefantrine, and mefloquine are effective against many strains of parasites resistant to chloroquine [103][104][105]. In addition, some of these drugs are widely used in combination therapies with artemisinin derivatives, including artemether plus lumefantrine and artesunate plus amodiaquine, and provide synergistic antimalarial activity along with preventing the development of antimalarial drug resistance [106][107][108].
The site of action of artemisinin and its derivatives dihydroartemisinin, artemether, arteether, and artesunate is believed to be the parasite’s digestive vacuole, where these drugs can interfere with the FPIX complex, giving rise to RONS, leading to damage to nearby proteins, and still interacting with the mitochondrial electron transport chain of the parasite, enhancing RONS production, impairing mitochondrial functions, and killing the parasite [109][110][111].
Artemisinins act quickly and are very potent against blood-stage parasites. They are active against the sex stages of the parasite, which is important for blocking transmission [112][113]. However, due to their short half-life, these drugs are used in conjunction with other long-acting drugs that remain in the body for longer to fight potential remaining parasites [114][115].
Accordingly, studies show that primaquine increases the effect of combination therapy with artemisinin derivatives in eliminating malaria and reduces the risk of artemisinin-resistant infections [116].
Furthermore, only primaquine is recognized for completely eliminating P. vivax and P. ovale that form hypnozoites—the latent form of the parasite that remains in the liver and is responsible for disease relapse in individuals infected by these parasites—refractory to most drugs and for providing a radical cure [93][117]. Primaquine, an 8-aminoquinoline, can act directly on erythrocytes leading to massive production of RONS and consequent lipid peroxidation of the cytoskeleton and membrane, as well as hemolysis [118]. However, the use of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency can result in clinical manifestations of hemolysis, such as severe anemia, fatigue, jaundice, and acute renal failure, thereby limiting its use [119][120].
In this scenario, as a product of the normal host’s metabolism or from the metabolism of the parasite, or as an effect of pharmacological treatment, intensely produced RONS cause damage to lipids, proteins, and DNA, leading to oxidative stress that impairs the normal functioning of the infected organism [98]. Therefore, the search for adjuvant therapies that can improve the clinical outcomes of malaria continues because, despite their benefits, treatments eventually cause oxidative damage, which limits their use [121].

3.5. Nitric Oxide in Malaria

Scientific evidence demonstrates that a specific RONS is particularly involved in the pathophysiology of this disease: NO [122][123]. It has been suggested that the low bioavailability of NO promotes oxidative stress in tissues such as the brain and lungs [124]. On the other hand, it has been shown that NO at high concentrations can kill Plasmodium [125][126]. NO is an important mediator of biological processes such as vascular homeostasis, neurotransmission, immunity, and inflammation [127][128][129]. Furthermore, it is a free radical produced by three different nitric oxide synthase enzymes, neuronal NOS (nNOS or NOS1), endothelial NOS (eNOS or NOS3), which are constitutively expressed, and the inducible NOS (iNOS or NOS2), which is induced by inflammatory stimuli [130][131][132][133]. NO is very reactive and has a very short half-life. For this reason, nitrite and nitrate measurements, which are the final metabolites of NO, have been used to measure the concentration of NO indirectly [134][135].
Experimental evidence indicates that NO plays an important role in the defense against plasmodia in vitro and in vivo [136][137]. In this context, studies have shown that circulating levels of nitrite and nitrate were higher in anopheline mosquitoes—a natural vector of malaria in humans—infected with Plasmodium and that increased NO concentrations at the beginning of the sporozoite stage induced the formation of toxic metabolites, limiting parasite development [138].
In children and adults with malaria, elevated plasma levels of nitrites and nitrates have been associated with more rapid parasite clearance [139]. Indeed, previous studies have shown that children infected with P. falciparum had elevated levels of NO and iNOS activity, suggesting the protective role of NO in children with malaria [140]. Protection against severe malaria in this population of children appears to be associated, at least in part, with a polymorphism in the iNOS gene, which produces high levels of NO during an inflammatory event [141]. These studies suggest that NO production during malaria depends on the severity of the disease and the degree of patient immunity [142].
In an animal model of experimental cerebral malaria (ECM), Serghides et al. [143] demonstrated that pretreatment with inhaled NO reduced the accumulation of parasitized erythrocytes in the brain, decreased endothelial cell expression, and preserved vascular integrity. From these results, the authors suggested that prophylaxis with NO inhalation can reduce systemic inflammation and endothelial activation during ECM. In a similar model, Ong et al. [144] showed that cerebrovascular dysfunction is characterized by vascular constriction, occlusion, and cell damage, resulting in impaired perfusion and reduced cerebral blood flow and oxygenation, and was associated with low NO bioavailability.
Given the critical importance of NO-derived and -non-derived oxidative stress in the underlying pathophysiological mechanisms of the disease, studies have shown that natural or synthetic exogenous antioxidants, including vitamin A, E, zinc, selenium, NAC, curcumin, Agaricus sylvaticus mushroom, and carotenoids, can benefit the treatment of malaria [145][146][147][148]. Several studies have indicated an association between the use of carotenoids and a decrease in oxidative changes, suggesting that the antioxidant properties of these compounds are an important factor against malaria-induced oxidative stress [149][150]. The recent interest in carotenoids has focused on the role of lycopene in human health [151][152].

4. Lycopene

Lycopene is a natural constituent synthesized by plants and microorganisms [153]. It is a red pigment found in some fruits and vegetables, such as guava, watermelon, papaya, pitanga (Eugenia uniflora—Myrtaceae), tomatoes, and their derivatives [154][155][156][157] and can be extracted from these vegetables by chemical reactions using organic solvents, such as ethanol and ethyl acetate and/or using a supercritical fluid such as supercritical carbon dioxide, or by heat treatment at different temperatures ranging from 60 to 140 °C [158][159][160][161][162][163]. It is widely used as a supplement in functional foods, nutraceuticals, and pharmaceuticals, as well as an additive in cosmetics [164][165].
Lycopene is an intermediate product of the β-carotene biosynthetic pathway that does not have provitamin A activity, as it does not have the β-ionone ring in its structure, which is responsible for this characteristic [166]. This compound is a noncyclic, fat-soluble hydrocarbon that contains 11 conjugated double bonds and 2 unconjugated double bonds, thereby offering it greater reactivity. This polyene can also exist in all-trans and cis-lycopene isomeric forms (Figure 6). Conversion from all-trans- to cis-lycopene forms can occur by geometric isomerism induced by light, thermal energy, or chemical reactions [167][168].
Figure 6. All-trans-lycopene and cis-lycopene structures.

5. Antioxidant Effects of Lycopene

Among the carotenoids, lycopene is the most effective antioxidant against RONS and may contribute to preventing or reducing oxidative damage to cells and tissues in vivo and in vitro [169]. Evidence supports the role of lycopene as a potent antioxidant, capable of scavenging singlet oxygen (1O2) and other free radicals, such as ROO-, with a potential twice as high as β-carotene, and ten times as efficient as α -tocopherol, although lycopene circulates at much lower concentrations than vitamin E [170][171]. During the elimination of 1O2, energy is transferred from this radical to the lycopene molecule and, as it has an open chain with 11 conjugated double bonds in its structure, this favors stabilization of the unpaired electron of the radical by resonance [172][173]. Additionally, it was observed that lycopene effectively eliminates other RONS, such as OH•, O2•−, and ONOO- [174].
Furthermore, the lipophilic characteristic of lycopene favors its interaction with the lipid bilayer of the cell membrane, thereby preventing the breakdown of fatty acids and the oxidation of lipids, proteins, and DNA [175]. In this sense, Suwannalert et al. [176], investigating serum levels of lycopene and malondialdehyde (MDA) in elderly susceptible to oxidative stress, demonstrated that lycopene levels were inversely related to MDA levels. Additionally, Yonar and Sakin [172] demonstrated that lycopene treatment prevented deltamethrin-induced oxidative stress by decreasing MDA levels in fish (Cyprinus carpio) and significantly increasing SOD, CAT, and GSH-Px activities and the level of GSH. Similar results were found by Kujawska et al. [177], who reported that treatment with tomato extract enriched with lycopene was able to suppress the oxidative stress induced by N-nitrosodiethylamine in rats and increase the enzymatic antioxidant activity in these animals.

6. Effects of Lycopene on Malaria

The use of antioxidant compounds in the treatment of tropical diseases has increased, including Chagas disease, dengue, and malaria, as several studies have suggested the involvement of oxidative stress in the pathogenesis and progression of these diseases [54][178][179]. In this context, studies show that the discovery of new antimalarial drugs is necessary, and natural antioxidant products are important sources for obtaining new antimalarial compounds or even as adjuvant therapy, enhancing the activity of antimalarial drugs [180][181][182][183][184].
A study by Metzger et al. [34] demonstrated that natural products can be used in malaria chemotherapy. According to this study, increased plasma lycopene concentration was associated with faster clearance of parasites in children. In a related study, Caulfield et al. [185] demonstrated that the nutritional deficiency of the host is associated with the morbidity and mortality of children with severe malaria. In this sense, previous studies suggest that changes in plasma concentrations of micronutrients, including vitamins A and C, retinol, β-carotene, α-carotene, β-cryptoxanthin, lutein, and lycopene, occur due to increased use of these antioxidants in patients with malaria, suggesting that there may be a need for vitamin supplementation in patients with malaria [186]. In corroborating this suggestion, the nutritional deficit seems to be associated with a redirection of these antioxidants to the liver to aid in the synthesis of acute-phase proteins in other organs, repair tissue damage caused by the infectious organism, and aid in the host’s oxidative defense mechanisms [33].
In fact, Sondo et al. [32] had already reported that periodic supplementation of high doses of vitamin A and zinc could reduce the morbidity caused by malaria. In this sense, Agarwal et al. [147] investigated the effect of lycopene on the growth of P. falciparum in vitro, monitoring the progression at different stages. These authors showed that lycopene treatment induced an increased production of RONS in the cytoplasm of the parasite, which caused the parasite to lose its mitochondrial membrane potential and cytotoxicity, resulting in merozoites not being released from the erythrocytes of the host, suggesting that the inclusion of lycopene in the diet may be useful in changing the clinical outcomes of malaria.
Preliminary results from researchers' group demonstrated that lycopene supplementation in mice (BALB/c; 3.11 mg/kg) infected with the P. berghei strain showed a delay in the induction and a decreased progression of parasitemia. Also, the animals supplemented with lycopene showed a higher rate of survival compared to the positive control [187], suggesting lycopene prophylactic and antiparasitic activity, which may be due to the cytotoxic effect of lycopene against the parasite [147], suggesting an important role of lycopene supplementation in preventing malaria [188].

References

  1. WHO. Word Malaria Report 2021; World Health Organization: Geneva, Switzerland, 2021.
  2. Griffiths, M.J.; Shafi, M.J.; Popper, S.J.; Hemingway, C.A.; Kortok, M.M.; Wathen, A.; Rockett, K.A.; Mott, R.; Levin, M.; Newton, C.R.; et al. Genomewide Analysis of the Host Response to Malaria in Kenyan Children. J. Infect. Dis. 2005, 191, 1599–1611.
  3. van Wolfswinkel, M.E.; Langenberg, M.C.C.; Wammes, L.J.; Sauerwein, R.W.; Koelewijn, R.; Hermsen, C.C.; van Hellemond, J.J.; van Genderen, P.J. Changes in Total and Differential Leukocyte Counts during the Clinically Silent Liver Phase in a Controlled Human Malaria Infection in Malaria-Naïve Dutch Volunteers. Malar. J. 2017, 16, 457.
  4. Aitken, E.H.; Alemu, A.; Rogerson, S.J. Neutrophils and Malaria. Front. Immunol. 2018, 9, 3005.
  5. Gonçalves, R.M.; Scopel, K.K.G.; Bastos, M.S.; Ferreira, M.U. Cytokine Balance in Human Malaria: Does Plasmodium Vivax Elicit More Inflammatory Responses than Plasmodium falciparum? PLoS ONE 2012, 7, e44394.
  6. Oyegue-Liabagui, S.L.; Bouopda-Tuedom, A.G.; Kouna, L.C.; Maghendji-Nzondo, S.; Nzoughe, H.; Tchitoula-Makaya, N.; Pegha-Moukandja, I.; Lekana-Douki, J.-B. Pro- and Anti-Inflammatory Cytokines in Children with Malaria in Franceville, Gabon. Am. J. Clin. Exp. Immunol. 2017, 6, 9–20.
  7. Nahrendorf, W.; Ivens, A.; Spence, P.J. Inducible Mechanisms of Disease Tolerance Provide an Alternative Strategy of Acquired Immunity to Malaria. eLife 2021, 10, e63838.
  8. Torre, D.; Speranza, F.; Giola, M.; Matteelli, A.; Tambini, R.; Biondi, G. Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria. Clin. Diagn. Lab. Immunol. 2002, 9, 348–351.
  9. John, C.C.; Park, G.S.; Sam-Agudu, N.; Opoka, R.O.; Boivin, M.J. Elevated Serum Levels of IL-1ra in Children with Plasmodium falciparum Malaria Are Associated with Increased Severity of Disease. Cytokine 2008, 41, 204–208.
  10. Dieye, Y.; Mbengue, B.; Dagamajalu, S.; Fall, M.M.; Loke, M.F.; Nguer, C.M.; Thiam, A.; Vadivelu, J.; Dieye, A. Cytokine Response during Non-Cerebral and Cerebral Malaria: Evidence of a Failure to Control Inflammation as a Cause of Death in African Adults. PeerJ 2016, 2016, e1965.
  11. Mandala, W.L.; Msefula, C.L.; Gondwe, E.N.; Drayson, M.T.; Molyneux, M.E.; MacLennan, C.A. Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria. Clin. Vaccine Immunol. 2017, 24, e00533-16.
  12. Couper, K.N.; Blount, D.G.; Wilson, M.S.; Hafalla, J.C.; Belkaid, Y.; Kamanaka, M.; Flavell, R.A.; De Souza, J.B.; Riley, E.M. IL-10 from CD4+CD25-Foxp3-CD127—Adaptive Regulatory T Cells Modulates Parasite Clearance and Pathology during Malaria Infection. PLoS Pathog. 2008, 4, e1000004.
  13. Bakir, H.Y.; Tomiyama, C.; Abo, T. Cytokine Profile of Murine Malaria: Stage-Related Production of Inflammatory and Anti-Inflammatory Cytokines. Biomed. Res. 2011, 32, 203–208.
  14. Gonçalves, R.M.; Lima, N.F.; Ferreira, M.U. Parasite Virulence, Co-Infections and Cytokine Balance in Malaria. Pathog. Glob. Health 2014, 108, 173–178.
  15. Perera, M.K.; Herath, N.P.; Pathirana, S.L.; Phone-Kyaw, M.; Alles, H.K.; Mendis, K.N.; Premawansa, S.; Handunnetti, S.M. Association of High Plasma TNF-Alpha Levels and TNF-Alpha/IL-10 Ratios with TNF2 Allele in Severe P. Falciparum Malaria Patients in Sri Lanka. Pathog. Glob. Health 2013, 107, 21–29.
  16. Herbert, F.; Tchitchek, N.; Bansal, D.; Jacques, J.; Pathak, S.; Bécavin, C.; Fesel, C.; Dalko, E.; Cazenave, P.A.; Preda, C.; et al. Evidence of IL-17, IP-10, and IL-10 Involvement in Multiple-Organ Dysfunction and IL-17 Pathway in Acute Renal Failure Associated to Plasmodium falciparum Malaria. J. Transl. Med. 2015, 13, 369.
  17. Lugrin, J.; Rosenblatt-Velin, N.; Parapanov, R.; Liaudet, L. The Role of Oxidative Stress during Inflammatory Processes. Biol. Chem. 2014, 395, 203–230.
  18. Ashok, G.R.; Samruddhi, M.; Shreewardhan, R.; Mira, R.; Abhay, C.; Ranjana, D. Influence of MDA and Pro-Inflammatory Cytokine Levels in the Pathogenesis of Severe Malaria in Experimental Murine Model. Scholars Acad. J. Biosc. 2016, 4, 617–626.
  19. Ty, M.C.; Zuniga, M.; Götz, A.; Kayal, S.; Sahu, P.K.; Mohanty, A.; Mohanty, S.; Wassmer, S.C.; Rodriguez, A. Malaria Inflammation by Xanthine Oxidase-produced Reactive Oxygen Species. EMBO Mol. Med. 2019, 11, e9903.
  20. Haldar, K.; Murphy, S.C.; Milner, D.A.; Taylor, T.E. Malaria: Mechanisms of Erythrocytic Infection and Pathological Correlates of Severe Disease. Annu. Rev. Pathol. Mech. Dis. 2007, 2, 217–249.
  21. Narsaria, N.; Mohanty, C.; Das, B.K.; Mishra, S.P.; Prasad, R. Oxidative Stress in Children with Severe Malaria. J. Trop. Pediatr. 2012, 58, 147–150.
  22. Srivastava, A.; Creek, D.J.; Evans, K.J.; De Souza, D.; Schofield, L.; Müller, S.; Barrett, M.P.; McConville, M.J.; Waters, A.P. Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites. PLoS Pathog. 2015, 11, e1004882.
  23. Clark, I.A.; Budd, A.C.; Alleva, L.M.; Cowden, W.B. Human Malarial Disease: A Consequence of Inflammatory Cytokine Release. Malar. J. 2006, 5, 85.
  24. Jain, V.; Singh, P.P.; Silawat, N.; Patel, R.; Saxena, A.; Bharti, P.K.; Shukla, M.; Biswas, S.; Singh, N. A Preliminary Study on Pro- and Anti-Inflammatory Cytokine Profiles in Plasmodium Vivax Malaria Patients from Central Zone of India. Acta Trop. 2010, 113, 263–268.
  25. Portugal, S.; Moebius, J.; Skinner, J.; Doumbo, S.; Doumtabe, D.; Kone, Y.; Dia, S.; Kanakabandi, K.; Sturdevant, D.E.; Virtaneva, K.; et al. Exposure-Dependent Control of Malaria-Induced Inflammation in Children. PLoS Pathog. 2014, 10, e1004079.
  26. Tekwani, B.L.; Walker, L.A. Targeting the Hemozoin Synthesis Pathway for New Antimalarial Drug Discovery: Technologies for in Vitro β-Hematin Formation Assay. Comb. Chem. High Throughput Screen. 2005, 8, 63–79.
  27. Gomes, A.R.Q.; Cunha, N.; Varela, E.L.P.; Brígido, H.P.C.; Vale, V.V.; Dolabela, M.F.; De Carvalho, E.P.; Percário, S. Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy. Int. J. Mol. Sci. 2022, 23, 5949.
  28. Nussenblatt, V.; Mukasa, G.; Metzger, A.; Ndeezi, G.; Eisinger, W.; Semba, R.D. Relationship between Carotenoids and Anaemia during Acute Uncomplicated Plasmodium falciparum Malaria in Children. J. Health Popul. Nutr. 2002, 20, 205–214.
  29. Gies, S.; Diallo, S.; Roberts, S.A.; Kazienga, A.; Powney, M.; Brabin, L.; Ouedraogo, S.; Swinkels, D.W.; Geurts-Moespot, A.J.; Claeys, Y.; et al. Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial. J. Infect. Dis. 2018, 218, 1099–1109.
  30. Iribhogbe, O.I.; Agbaje, E.O.; Oreagba, I.A.; Aina, O.O.; Ota, A.D. Oxidative Stress and Micronutrient Therapy in Malaria: An In Vivo Study in Plasmodium Berghei Infected Mice. Pak. J. Biol. Sci. 2013, 16, 160–167.
  31. Shankar, A.H.; Genton, B.; Baisor, M.; Jaino, P.; Tamja, S.; Adiguma, T.; Wu, L.; Rare, L.; Bannon, D.; Tielsch, J.M.; et al. The Influence of Zinc Supplementation on Morbidity Due to Plasmodium falciparum: A Randomized Trial in Preschool Children in Papua New Guinea. Am. J. Trop. Med. Hyg. 2000, 62, 663–669.
  32. Sondo, P.; Tahita, M.C.; Rouamba, T.; Derra, K.; Kaboré, B.; Compaoré, C.S.; Ouédraogo, F.; Rouamba, E.; Ilboudo, H.; Bambara, E.A.; et al. Assessment of a Combined Strategy of Seasonal Malaria Chemoprevention and Supplementation with Vitamin A, Zinc and Plumpy’DozTM to Prevent Malaria and Malnutrition in Children under 5 Years Old in Burkina Faso: A Randomized Open-Label Trial (SMC-NUT). Trials 2021, 22, 360.
  33. Das, B.S.; Thurnham, D.I.; Das, D.B. Plasma α-Tocopherol, Retinol, and Carotenoids in Children with Falciparum Malaria. Am. J. Clin. Nutr. 1996, 64, 94–100.
  34. Metzger, A.; Mukasa, G.; Shankar, A.H.; Ndeezi, G.; Melikian, G.; Semba, R.D. Antioxidant Status and Acute Malaria in Children in Kampala, Uganda. Am. J. Trop. Med. Hyg. 2001, 65, 115–119.
  35. Halliwell, B. Biochemistry of Oxidative Stress. Biochem. Soc. Trans. 2007, 35, 1147–1150.
  36. Sies, H.; Berndt, C.; Jones, D.P. Oxidative Stress. Annu. Rev. Biochem. 2017, 86, 715–748.
  37. Kowaltowski, A.J.; de Souza-Pinto, N.C.; Castilho, R.F.; Vercesi, A.E. Mitochondria and Reactive Oxygen Species. Free Radic. Biol. Med. 2009, 47, 333–343.
  38. Scherz-Shouval, R.; Elazar, Z. Regulation of Autophagy by ROS: Physiology and Pathology. Trends Biochem. Sci. 2011, 36, 30–38.
  39. Powers, S.K.; Jackson, M.J. Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production. Physiol. Rev. 2008, 88, 1243–1276.
  40. Nathan, C.; Ding, A. SnapShot: Reactive Oxygen Intermediates (ROI). Cell 2010, 140, 952.e2.
  41. Ighodaro, O.M.; Akinloye, O.A. First Line Defence Antioxidants-Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX): Their Fundamental Role in the Entire Antioxidant Defence Grid. Alexandria J. Med. 2018, 54, 287–293.
  42. York-Duran, M.J.; Godoy-Gallardo, M.; Jansman, M.M.T.; Hosta-Rigau, L. A Dual-Component Carrier with Both Non-Enzymatic and Enzymatic Antioxidant Activity towards ROS Depletion. Biomater. Sci. 2019, 7, 4813–4826.
  43. Rizvi, S.I.; Maurya, P.K. Alterations in Antioxidant Enzymes During Aging in Humans. Mol. Biotechnol. 2007, 37, 58–61.
  44. Gęgotek, A.; Nikliński, J.; Žarković, N.; Žarković, K.; Waeg, G.; Łuczaj, W.; Charkiewicz, R.; Skrzydlewska, E. Lipid Mediators Involved in the Oxidative Stress and Antioxidant Defence of Human Lung Cancer Cells. Redox Biol. 2016, 9, 210–219.
  45. Kurutas, E.B. The Importance of Antioxidants Which Play the Role in Cellular Response against Oxidative/Nitrosative Stress: Current State. Nutr. J. 2015, 15, 71.
  46. Aninagyei, E.; Tettey, C.O.; Kwansa-Bentum, H.; Boakye, A.A.; Ghartey-Kwansah, G.; Boye, A.; Acheampong, D.O. Oxidative Stress and Associated Clinical Manifestations in Malaria and Sickle Cell (HbSS) Comorbidity. PLoS ONE 2022, 17, e0269720.
  47. Kasperczyk, S.; Dobrakowski, M.; Kasperczyk, A.; Zalejska-Fiolka, J.; Pawlas, N.; Kapka-Skrzypczak, L.; Birkner, E. Effect of Treatment with N-Acetylcysteine on Non-Enzymatic Antioxidant Reserves and Lipid Peroxidation in Workers Exposed to Lead. Ann. Agric. Environ. Med. 2014, 21, 272–277.
  48. Mirończuk-Chodakowska, I.; Witkowska, A.M.; Zujko, M.E. Endogenous Non-Enzymatic Antioxidants in the Human Body. Adv. Med. Sci. 2018, 63, 68–78.
  49. Nimse, S.B.; Pal, D. Free Radicals, Natural Antioxidants, and Their Reaction Mechanisms. RSC Adv. 2015, 5, 27986–28006.
  50. Csányi, G.; Miller, F.J., Jr. Oxidative Stress in Cardiovascular Disease. Int. J. Mol. Sci. 2014, 15, 6002–6008.
  51. Ghavipour, M.; Sotoudeh, G.; Tavakoli, E.; Mowla, K.; Hasanzadeh, J.; Mazloom, Z. Pomegranate Extract Alleviates Disease Activity and Some Blood Biomarkers of Inflammation and Oxidative Stress in Rheumatoid Arthritis Patients. Eur. J. Clin. Nutr. 2017, 71, 92–96.
  52. Kremsner, P.G.; Greve, B.; Lell, B.; Luckner, D.; Schmid, D. Malarial Anaemia in African Children Associated with High Oxygen-Radical Production. Lancet 2000, 355, 40–41.
  53. Guha, M.; Kumar, S.; Choubey, V.; Maity, P.; Bandyopadhyay, U.; Guha, M.; Kumar, S.; Choubey, V.; Maity, P.; Bandyopadhyay, U. Apoptosis in Liver during Malaria: Role of Oxidative Stress and Implication of Mitochondrial Pathway. FASEB J. 2006, 20, 1224–1226.
  54. Percário, S.; Moreira, D.; Gomes, B.; Ferreira, M.; Gonçalves, A.; Laurindo, P.; Vilhena, T.; Dolabela, M.; Green, M. Oxidative Stress in Malaria. Int. J. Mol. Sci. 2012, 13, 16346–16372.
  55. Yang, Y.; Bazhin, A.V.; Werner, J.; Karakhanova, S. Reactive Oxygen Species in the Immune System. Int. Rev. Immunol. 2013, 32, 249–270.
  56. Casas, A.I.; Nogales, C.; Mucke, H.A.M.; Petraina, A.; Cuadrado, A.; Rojo, A.I.; Ghezzi, P.; Jaquet, V.; Augsburger, F.; Dufrasne, F.; et al. On the Clinical Pharmacology of Reactive Oxygen Species. Pharmacol. Rev. 2020, 72, 801–828.
  57. Leoratti, F.M.D.S.; Trevelin, S.C.; Cunha, F.Q.; Rocha, B.C.; Costa, P.A.C.; Gravina, H.D.; Tada, M.S.; Pereira, D.B.; Golenbock, D.T.; do Valle Antonelli, L.R.; et al. Neutrophil Paralysis in Plasmodium Vivax Malaria. PLoS Negl. Trop. Dis. 2012, 6, e1710.
  58. Chua, C.L.L.; Ng, I.M.J.; Yap, B.J.M.; Teo, A. Factors Influencing Phagocytosis of Malaria Parasites: The Story so Far. Malar. J. 2021, 20, 319.
  59. Zelter, T.; Strahilevitz, J.; Simantov, K.; Yajuk, O.; Adams, Y.; Ramstedt Jensen, A.; Dzikowski, R.; Granot, Z. Neutrophils Impose Strong Immune Pressure against PfEMP1 Variants Implicated in Cerebral Malaria. EMBO Rep. 2022, 23, e53641.
  60. Joos, C.; Marrama, L.; Polson, H.E.J.; Corre, S.; Diatta, A.M.; Diouf, B.; Trape, J.F.; Tall, A.; Longacre, S.; Perraut, R. Clinical Protection from Falciparum Malaria Correlates with Neutrophil Respiratory Bursts Induced by Merozoites Opsonized with Human Serum Antibodies. PLoS ONE 2010, 5, e9871.
  61. Chen, L.; Zhang, Z.-H.; Sendo, F. Neutrophils Play a Critical Role in the Pathogenesis of Experimental Cerebral Malaria. Clin. Exp. Immunol. 2001, 120, 125–133.
  62. Su, Z.; Fortin, A.; Gros, P.; Stevenson, M.M. Opsonin-Independent Phagocytosis: An Effector Mechanism against Acute Blood-Stage Plasmodium chabaudi AS Infection. J. Infect. Dis. 2002, 186, 1321–1329.
  63. Sponaas, A.M.; Do Rosario, A.P.F.; Voisine, C.; Mastelic, B.; Thompson, J.; Koernig, S.; Jarra, W.; Renia, L.; Mauduit, M.; Potocnik, A.J.; et al. Migrating Monocytes Recruited to the Spleen Play an Important Role in Control of Blood Stage Malaria. Blood 2009, 114, 5522–5531.
  64. Weinberg, J.B.; Volkheimer, A.D.; Rubach, M.P.; Florence, S.M.; Mukemba, J.P.; Kalingonji, A.R.; Langelier, C.; Chen, Y.; Bush, M.; Yeo, T.W.; et al. Monocyte Polarization in Children with Falciparum Malaria: Relationship to Nitric Oxide Insufficiency and Disease Severity. Sci. Rep. 2016, 6, 29151.
  65. Molina-Cruz, A.; DeJong, R.J.; Charles, B.; Gupta, L.; Kumar, S.; Jaramillo-Gutierrez, G.; Barillas-Mury, C. Reactive Oxygen Species Modulate Anopheles Gambiae Immunity against Bacteria and Plasmodium. J. Biol. Chem. 2008, 283, 3217–3223.
  66. Dupré-Crochet, S.; Erard, M.; Nüβe, O. ROS Production in Phagocytes: Why, When, and Where? J. Leukoc. Biol. 2013, 94, 657–670.
  67. Becker, K.; Tilley, L.; Vennerstrom, J.L.; Roberts, D.; Rogerson, S.; Ginsburg, H. Oxidative Stress in Malaria Parasite-Infected Erythrocytes: Host–Parasite Interactions. Int. J. Parasitol. 2004, 34, 163–189.
  68. Ortega-Pajares, A.; Rogerson, S.J. The Rough Guide to Monocytes in Malaria Infection. Front. Immunol. 2018, 9, 2888.
  69. Eltzschig, H.K.; Eckle, T. Ischemia and Reperfusion—From Mechanism to Translation. Nat. Med. 2011, 17, 1391–1401.
  70. Sanni, L.A.; Rae, C.; Maitland, A.; Stocker, R.; Hunt, N.H. Is Ischemia Involved in the Pathogenesis of Murine Cerebral Malaria? Am. J. Pathol. 2001, 159, 1105–1112.
  71. Carden, D.L.; Granger, D.N. Pathophysiology of Ischaemia-Reperfusion Injury. J. Pathol. 2000, 190, 255–266.
  72. Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Cell Biology of Ischemia/Reperfusion Injury. Int. Rev. Cell Mol. Biol. 2012, 298, 229–317.
  73. Kelley, E.E.; Khoo, N.K.H.; Hundley, N.J.; Malik, U.Z.; Freeman, B.A.; Tarpey, M.M. Hydrogen Peroxide Is the Major Oxidant Product of Xanthine Oxidase. Free Radic. Biol. Med. 2010, 48, 493–498.
  74. Schmidt, H.M.; Kelley, E.E.; Straub, A.C. The Impact of Xanthine Oxidase (XO) on Hemolytic Diseases. Redox Biol. 2019, 21, 101072.
  75. Orengo, J.M.; Leliwa-Sytek, A.; Evans, J.E.; Evans, B.; van de Hoef, D.; Nyako, M.; Day, K.; Rodriguez, A. Uric Acid Is a Mediator of the Plasmodium falciparum-Induced Inflammatory Response. PLoS ONE 2009, 4, e5194.
  76. Hong, Q.; Qi, K.; Feng, Z.; Huang, Z.; Cui, S.; Wang, L.; Fu, B.; Ding, R.; Yang, J.; Chen, X.; et al. Hyperuricemia Induces Endothelial Dysfunction via Mitochondrial Na+/Ca2+ Exchanger-Mediated Mitochondrial Calcium Overload. Cell Calcium 2012, 51, 402–410.
  77. Ayede, A.; Amoo, B.; Anetor, J.; Adeola, A. Status of Some Basic Antioxidants in Pre- and Postmalaria Treatment in Children. J. Child Sci. 2018, 08, e31–e35.
  78. Lopera-Mesa, T.M.; Mita-Mendoza, N.K.; van de Hoef, D.L.; Doumbia, S.; Konaté, D.; Doumbouya, M.; Gu, W.; Traoré, K.; Diakité, S.A.S.; Remaley, A.T.; et al. Plasma Uric Acid Levels Correlate with Inflammation and Disease Severity in Malian Children with Plasmodium falciparum Malaria. PLoS ONE 2012, 7, e46424.
  79. Mita-Mendoza, N.K.; van de Hoef, D.L.; Lopera-Mesa, T.M.; Doumbia, S.; Konate, D.; Doumbouya, M.; Gu, W.; Anderson, J.M.; Santos-Argumedo, L.; Rodriguez, A.; et al. A Potential Role for Plasma Uric Acid in the Endothelial Pathology of Plasmodium falciparum Malaria. PLoS ONE 2013, 8, e54481.
  80. Meneshian, A.; Bulkley, G.B. The Physiology of Endothelial Xanthine Oxidase: From Urate Catabolism to Reperfusion Injury to Inflammatory Signal Transduction. Microcirculation 2002, 9, 161–175.
  81. Bakar, N.A.; Klonis, N.; Hanssen, E.; Chan, C.; Tilley, L. Digestive-Vacuole Genesis and Endocytic Processes in the Early Intraerythrocytic Stages of Plasmodium falciparum. J. Cell Sci. 2010, 123, 441–450.
  82. Jonscher, E.; Flemming, S.; Schmitt, M.; Sabitzki, R.; Reichard, N.; Birnbaum, J.; Bergmann, B.; Höhn, K.; Spielmann, T. PfVPS45 Is Required for Host Cell Cytosol Uptake by Malaria Blood Stage Parasites. Cell Host Microbe 2019, 25, 166–173.e5.
  83. Kumar, S.; Bandyopadhyay, U. Free Heme Toxicity and Its Detoxification Systems in Human. Toxicol. Lett. 2005, 157, 175–188.
  84. Kehrer, J.P. The Haber-Weiss Reaction and Mechanisms of Toxicity. Toxicology 2000, 149, 43–50.
  85. Gupta, M.; Kumar, S.; Kumar, R.; Kumar, A.; Verma, R.; Darokar, M.P.; Rout, P.; Pal, A. Inhibition of Heme Detoxification Pathway in Malaria Parasite by 3-Hydroxy-11-Keto-β-Boswellic Acid Isolated from Boswellia Serrata. Biomed. Pharmacother. 2021, 144, 112302.
  86. Dondorp, A.M.; Omodeo-Salè, F.; Chotivanich, K.; Taramelli, D.; White, N.J. Oxidative Stress and Rheology in Severe Malaria. Red. Rep. 2003, 8, 292–294.
  87. Nuchsongsin, F.; Chotivanich, K.; Charunwatthana, P.; Fausta, O.S.; Taramelli, D.; Day, N.P.; White, N.J.; Dondorp, A.M. Effects of Malaria Heme Products on Red Blood Cell Deformability. Am. J. Trop. Med. Hyg. 2007, 77, 617–622.
  88. Cadet, J.; Douki, T.; Ravanat, J.-L. Oxidatively Generated Base Damage to Cellular DNA. Free Radic. Biol. Med. 2010, 49, 9–21.
  89. Rahal, A.; Kumar, A.; Singh, V.; Yadav, B.; Tiwari, R.; Chakraborty, S.; Dhama, K. Oxidative Stress, Prooxidants, and Antioxidants: The Interplay. Biomed Res. Int. 2014, 2014, 761264.
  90. Dondorp, A.M.; Kager, P.A.; Vreeken, J.; White, N.J. Abnormal Blood Flow and Red Blood Cell Deformability in Severe Malaria. Parasitol. Today 2000, 16, 228–232.
  91. Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.D.; Mazur, M.; Telser, J. Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. Int. J. Biochem. Cell Biol. 2007, 39, 44–84.
  92. Kavishe, R.A.; Koenderink, J.B.; Alifrangis, M. Oxidative Stress in Malaria and Artemisinin Combination Therapy: Pros and Cons. FEBS J. 2017, 284, 2579–2591.
  93. Campo, B.; Vandal, O.; Wesche, D.L.; Burrows, J.N. Killing the Hypnozoite—Drug Discovery Approaches to Prevent Relapse in Plasmodium Vivax. Pathog. Glob. Health 2015, 109, 107–122.
  94. John, C.C. Primaquine plus Artemisinin Combination Therapy for Reduction of Malaria Transmission: Promise and Risk. BMC Med. 2016, 14, 65.
  95. Sullivan, D.J. Theories on Malarial Pigment Formation and Quinoline Action. Int. J. Parasitol. 2002, 32, 1645–1653.
  96. Roepe, P.D. Molecular and Physiologic Basis of Quinoline Drug Resistance in Plasmodium falciparum Malaria. Future Microbiol. 2009, 4, 441–455.
  97. Fitch, C.D. Ferriprotoporphyrin IX, Phospholipids, and the Antimalarial Actions of Quinoline Drugs. Life Sci. 2004, 74, 1957–1972.
  98. Radfar, A.; Diez, A.; Bautista, J.M. Chloroquine Mediates Specific Proteome Oxidative Damage across the Erythrocytic Cycle of Resistant Plasmodium falciparum. Free Radic. Biol. Med. 2008, 44, 2034–2042.
  99. Acosta, M.E.; Gotopo, L.; Gamboa, N.; Rodrigues, J.R.; Henriques, G.C.; Cabrera, G.; Romero, A.H. Antimalarial Activity of Highly Coordinative Fused Heterocycles Targeting β–Hematin Crystallization. ACS Omega 2022, 7, 7499–7514.
  100. Durrand, V.; Berry, A.; Sem, R.; Glaziou, P.; Beaudou, J.; Fandeur, T. Variations in the Sequence and Expression of the Plasmodium falciparum Chloroquine Resistance Transporter (Pfcrt) and Their Relationship to Chloroquine Resistance in Vitro. Mol. Biochem. Parasitol. 2004, 136, 273–285.
  101. Lakshmanan, V.; Bray, P.G.; Verdier-Pinard, D.; Johnson, D.J.; Horrocks, P.; Muhle, R.A.; Alakpa, G.E.; Hughes, R.H.; Ward, S.A.; Krogstad, D.J.; et al. A Critical Role for PfCRT K76T in Plasmodium falciparum Verapamil-Reversible Chloroquine Resistance. EMBO J. 2005, 24, 2294–2305.
  102. Callaghan, P.S.; Hassett, M.R.; Roepe, P.D. Functional Comparison of 45 Naturally Occurring Isoforms of the Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT). Biochemistry 2015, 54, 5083–5094.
  103. Gorka, A.P.; De Dios, A.; Roepe, P.D. Quinoline Drug-Heme Interactions and Implications for Antimalarial Cytostatic versus Cytocidal Activities. J. Med. Chem. 2013, 56, 5231–5246.
  104. Parhizgar, A.R.; Tahghighi, A. Introducing New Antimalarial Analogues of Chloroquine and Amodiaquine: A Narrative Review. Iran. J. Med. Sci. 2017, 42, 115–128.
  105. Herraiz, T.; Guillén, H.; González-Peña, D.; Arán, V.J. Antimalarial Quinoline Drugs Inhibit β-Hematin and Increase Free Hemin Catalyzing Peroxidative Reactions and Inhibition of Cysteine Proteases. Sci. Rep. 2019, 9, 15398.
  106. Falade, C.O.; Ogundele, A.O.; Yusuf, B.O.; Ademowo, O.G.; Ladipo, S.M. High Efficacy of Two Artemisinin-Based Combinations (Artemether- Lumefantrine and Artesunate plus Amodiaquine) for Acute Uncomplicated Malaria in Ibadan, Nigeria. Trop. Med. Int. Health 2008, 13, 635–643.
  107. Makanga, M.; Krudsood, S. The Clinical Efficacy of Artemether/Lumefantrine (Coartem®). Malar. J. 2009, 8, S5.
  108. Egunsola, O.; Oshikoya, K.A. Comparative Safety of Artemether-Lumefantrine and Other Artemisinin-Based Combinations in Children: A Systematic Review. Malar. J. 2013, 12, 385.
  109. Wang, J.; Huang, L.; Li, J.; Fan, Q.; Long, Y.; Li, Y.; Zhou, B. Artemisinin Directly Targets Malarial Mitochondria through Its Specific Mitochondrial Activation. PLoS ONE 2010, 5, e9582.
  110. Klonis, N.; Crespo-Ortiz, M.P.; Bottova, I.; Abu-Bakar, N.; Kenny, S.; Rosenthal, P.J.; Tilley, L. Artemisinin Activity against Plasmodium falciparum Requires Hemoglobin Uptake and Digestion. Proc. Natl. Acad. Sci. USA 2011, 108, 11405–11410.
  111. Yang, J.; He, Y.; Li, Y.; Zhang, X.; Wong, Y.-K.; Shen, S.; Zhong, T.; Zhang, J.; Liu, Q.; Wang, J. Advances in the Research on the Targets of Anti-Malaria Actions of Artemisinin. Pharmacol. Ther. 2020, 216, 107697.
  112. Pukrittayakamee, S.; Chotivanich, K.; Chantra, A.; Clemens, R.; Looareesuwan, S.; White, N.J. Activities of Artesunate and Primaquine against Asexual- and Sexual-Stage Parasites in Falciparum Malaria. Antimicrob. Agents Chemother. 2004, 48, 1329–1334.
  113. Delves, M.; Plouffe, D.; Scheurer, C.; Meister, S.; Wittlin, S.; Winzeler, E.A.; Sinden, R.E.; Leroy, D. The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites. PLoS Med. 2012, 9, e1001169.
  114. Okell, L.C.; Drakeley, C.J.; Bousema, T.; Whitty, C.J.M.; Ghani, A.C. Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity. PLoS Med. 2008, 5, 1617–1628.
  115. Dodoo, A.N.O.; Fogg, C.; Asiimwe, A.; Nartey, E.T.; Kodua, A.; Tenkorang, O.; Ofori-Adjei, D. Pattern of Drug Utilization for Treatment of Uncomplicated Malaria in Urban Ghana Following National Treatment Policy Change to Artemisinin-Combination Therapy. Malar. J. 2009, 8, 2.
  116. Maude, R.J.; Socheat, D.; Nguon, C.; Saroth, P.; Dara, P.; Li, G.; Song, J.; Yeung, S.; Dondorp, A.M.; Day, N.P.; et al. Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance. PLoS ONE 2012, 7, e37166.
  117. Lödige, M.; Lewis, M.D.; Paulsen, E.S.; Esch, H.L.; Pradel, G.; Lehmann, L.; Brun, R.; Bringmann, G.; Mueller, A.K. A Primaquine-Chloroquine Hybrid with Dual Activity against Plasmodium Liver and Blood Stages. Int. J. Med. Microbiol. 2013, 303, 539–547.
  118. Milner, E.E.; Berman, J.; Caridha, D.; Dickson, S.P.; Hickman, M.; Lee, P.J.; Marcsisin, S.R.; Read, L.T.; Roncal, N.; Vesely, B.A.; et al. Cytochrome P450 2D-Mediated Metabolism Is Not Necessary for Tafenoquine and Primaquine to Eradicate the Erythrocytic Stages of Plasmodium berghei. Malar. J. 2016, 15, 588.
  119. Shekalaghe, S.A.; Braak, R.T.; Daou, M.; Kavishe, R.; Van Bijllaardt, W.D.; Van Bosch, S.D.; Koenderink, J.B.; Luty, A.J.F.; Whitty, C.J.M.; Drakeley, C.; et al. In Tanzania, Hemolysis after a Single Dose of Primaquine Coadministered with an Artemisinin Is Not Restricted to Glucose-6-Phosphate Dehydrogenase-Deficient (G6PD A-) Individuals. Antimicrob. Agents Chemother. 2010, 54, 1762–1768.
  120. Brito-Sousa, J.D.; Santos, T.C.; Avalos, S.; Fontecha, G.; Melo, G.C.; Val, F.; Siqueira, A.M.; Alecrim, G.C.; Bassat, Q.; Lacerda, M.V.G.; et al. Clinical Spectrum of Primaquine-Induced Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficiency: A 9-Year Hospitalization-Based Study from the Brazilian Amazon. Clin. Infec. Dis. 2019, 69, 1440–1442.
  121. Farombi, E.O.; Shyntum, Y.Y.; Emerole, G.O. Influence of Chloroquine Treatment and Plasmodium falciparum Malaria Infection on Some Enzymatic and Non-Enzymatic Antioxidant Defense Indices in Humans. Drug Chem. Toxicol. 2003, 26, 59–71.
  122. Zanini, G.M.; Cabrales, P.; Barkho, W.; Frangos, J.A.; Carvalho, L.J.M. Exogenous Nitric Oxide Decreases Brain Vascular Inflammation, Leakage and Venular Resistance during Plasmodium Berghei ANKA Infection in Mice. J. Neuroinflamm. 2011, 8, 66.
  123. Moreira, D.R.; Uberti, A.C.M.G.; Gomes, A.R.Q.; Ferreira, M.E.S.; da Silva Barbosa, A.; Varela, E.L.P.; Dolabela, M.F.; Percário, S. Dexamethasone Increased the Survival Rate in Plasmodium berghei-Infected Mice. Sci. Rep. 2021, 11, 2623.
  124. Barbosa, A.D.S.; Temple, M.C.R.; Varela, E.L.P.; Gomes, A.R.Q.; Silveira, E.L.; de Carvalho, E.P.; Dolabela, M.F.; Percario, S. Inhibition of Nitric Oxide Synthesis Promotes Increased Mortality despite the Reduction of Parasitemia in Plasmodium berghei-Infected Mice. Res. Soc. Dev. 2021, 10, e27810111805.
  125. Fritsche, G.; Larcher, C.; Schennach, H.; Weiss, G. Regulatory Interactions between Iron and Nitric Oxide Metabolism for Immune Defense against Plasmodium falciparum Infection. J. Infect. Dis. 2001, 183, 1388–1394.
  126. Cabrales, P.; Zanini, G.M.; Meays, D.; Frangos, J.A.; Carvalho, L.J.M. Nitric Oxide Protection Against Murine Cerebral Malaria Is Associated with Improved Cerebral Microcirculatory Physiology. J. Infect. Dis. 2011, 203, 1454–1463.
  127. Coleman, J.W. Nitric Oxide in Immunity and Inflammation. Int. Immunopharmacol. 2001, 1, 1397–1406.
  128. Bian, K.; Doursout, M.-F.; Murad, F. Vascular System: Role of Nitric Oxide in Cardiovascular Diseases. J. Clin. Hypertens. 2008, 10, 304–310.
  129. Ahlawat, A.; Rana, A.; Goyal, N.; Sharma, S. Potential Role of Nitric Oxide Synthase Isoforms in Pathophysiology of Neuropathic Pain. Inflammopharmacology 2014, 22, 269–278.
  130. Bogdan, C. Nitric Oxide and the Immune Response. Nat. Immunol. 2001, 2, 907–916.
  131. Vallance, P.; Leiper, J. Blocking NO Synthesis: How, Where and Why? Nat. Rev. Drug Discov. 2002, 1, 939–950.
  132. Forstermann, U.; Sessa, W.C. Nitric Oxide Synthases: Regulation and Function. Eur. Heart J. 2012, 33, 829–837.
  133. Wong, V.C.; Lerner, E. Nitric Oxide Inhibition Strategies. Future Sci. OA 2015, 1, FSO35.
  134. Nahrevanian, H.; Dascombe, M.J. Nitric Oxide and Reactive Nitrogen Intermediates during Lethal and Nonlethal Strains of Murine Malaria. Parasite Immunol. 2001, 23, 491–501.
  135. Luckhart, S.; Crampton, A.L.; Zamora, R.; Lieber, M.J.; Dos Santos, P.C.; Peterson, T.M.L.; Emmith, N.; Lim, J.; Wink, D.A.; Vodovotz, Y. Mammalian Transforming Growth Factor Β1 Activated after Ingestion by Anopheles stephensi Modulates Mosquito Immunity. Infect. Immun. 2003, 71, 3000–3009.
  136. Kun, J.F.; Mordmüller, B.; Perkins, D.J.; May, J.; Mercereau-Puijalon, O.; Alpers, M.; Weinberg, J.B.; Kremsner, P.G. Nitric Oxide Synthase 2Lambaréné (G-954C), Increased Nitric Oxide Production, and Protection against Malaria. J. Infect. Dis. 2001, 184, 330–336.
  137. Gramaglia, I.; Sobolewski, P.; Meays, D.; Contreras, R.; Nolan, J.P.; Frangos, J.A.; Intaglietta, M.; Van Der Heyde, H.C. Low Nitric Oxide Bioavailability Contributes to the Genesis of Experimental Cerebral Malaria. Nat. Med. 2006, 12, 1417–1422.
  138. Peterson, T.M.L.; Gow, A.J.; Luckhart, S. Nitric Oxide Metabolites Induced in Anopheles Stephensi Control Malaria Parasite Infection. Free Radic. Biol. Med. 2007, 42, 132–142.
  139. Maurizio, P.L.; Fuseini, H.; Tegha, G.; Hosseinipour, M.; De Paris, K. Signatures of Divergent Anti-Malarial Treatment Responses in Peripheral Blood from Adults and Young Children in Malawi. Malar. J. 2019, 18, 205.
  140. Dzodzomenyo, M.; Ghansah, A.; Ensaw, N.; Dovie, B.; Bimi, L.; Quansah, R.; Gyan, B.A.; Gyakobo, M.; Amoani, B. Inducible Nitric Oxide Synthase 2 Promoter Polymorphism and Malaria Disease Severity in Children in Southern Ghana. PLoS ONE 2018, 13, e0202218.
  141. Hobbs, M.R.; Udhayakumar, V.; Levesque, M.C.; Booth, J.; Roberts, J.M.; Tkachuk, A.N.; Pole, A.; Coon, H.; Kariuki, S.; Nahlen, B.L.; et al. A New NOS2 Promoter Polymorphism Associated with Increased Nitric Oxide Production and Protection from Severe Malaria in Tanzanian and Kenyan Children. Lancet 2002, 360, 1468–1475.
  142. Clark, I.A.; Rockett, K.A.; Burgner, D. Genes, Nitric Oxide and Malaria in African Children. Trends Parasitol. 2003, 19, 335–337.
  143. Serghides, L.; Kim, H.; Lu, Z.; Kain, D.C.; Miller, C.; Francis, R.C.; Liles, W.C.; Zapol, W.M.; Kain, K.C. Inhaled Nitric Oxide Reduces Endothelial Activation and Parasite Accumulation in the Brain, and Enhances Survival in Experimental Cerebral Malaria. PLoS ONE 2011, 6, e27714.
  144. Ong, P.K.; Melchior, B.; Martins, Y.C.; Hofer, A.; Orjuela-Sánchez, P.; Cabrales, P.; Zanini, G.M.; Frangos, J.A.; Carvalho, L.J.M. Nitric Oxide Synthase Dysfunction Contributes to Impaired Cerebroarteriolar Reactivity in Experimental Cerebral Malaria. PLoS Pathog. 2013, 9, e1003444.
  145. Cui, L.; Miao, J.; Cui, L. Cytotoxic Effect of Curcumin on Malaria Parasite Plasmodium falciparum: Inhibition of Histone Acetylation and Generation of Reactive Oxygen Species. Antimicrob. Agents Chemother. 2007, 51, 488–494.
  146. Iribhogbe, O.L.; Agbaje, E.O.; Oreagba, I.A.; Aina, O.O.; Ota, A.D. Oxidant versus Antioxidant Activity in Malaria: Role of Nutritional Therapy. J. Med. Sci. 2012, 12, 229–233.
  147. Agarwal, S.; Sharma, V.; Kaul, T.; Abdin, M.Z.; Singh, S. Cytotoxic Effect of Carotenoid Phytonutrient Lycopene on P. falciparum Infected Erythrocytes. Mol. Biochem. Parasitol. 2014, 197, 15–20.
  148. Quadros Gomes, B.A.; Da Silva, L.F.D.; Quadros Gomes, A.R.; Moreira, D.R.; Dolabela, M.F.; Santos, R.S.; Green, M.D.; Carvalho, E.P.; Percário, S. N-Acetyl Cysteine and Mushroom Agaricus sylvaticus Supplementation Decreased Parasitaemia and Pulmonary Oxidative Stress in a Mice Model of Malaria. Malar. J. 2015, 14, 202.
  149. Krinsky, N.I.; Johnson, E.J. Carotenoid Actions and Their Relation to Health and Disease. Mol. Aspects Med. 2005, 26, 459–516.
  150. Bohn, T. Carotenoids and Markers of Oxidative Stress in Human Observational Studies and Intervention Trials: Implications for Chronic Diseases. Antioxidants 2019, 8, 179.
  151. Ferreira-Santos, P.; Aparicio, R.; Carrón, R.; Sevilla, M.Á.; Monroy-Ruiz, J.; Montero, M.J. Lycopene-Supplemented Diet Ameliorates Cardiovascular Remodeling and Oxidative Stress in Rats with Hypertension Induced by Angiotensin II. J. Funct. Foods 2018, 47, 279–287.
  152. Ni, Y.; Zhuge, F.; Nagashimada, M.; Nagata, N.; Xu, L.; Yamamoto, S.; Fuke, N.; Ushida, Y.; Suganuma, H.; Kaneko, S.; et al. Lycopene Prevents the Progression of Lipotoxicity-Induced Nonalcoholic Steatohepatitis by Decreasing Oxidative Stress in Mice. Free Radic. Biol. Med. 2020, 152, 571–582.
  153. Chen, J.; Pu, Z.; Xiao, Y.; Li, C.; Du, X.; Su, C.; Zhang, X. Lycopene Synthesis via Tri-Cistronic Expression of LeGGPS2, LePSY1 and CrtI in Escherichia coli. Shengwu Gongcheng Xuebao/Chin. J. Biotechnol. 2012, 28, 823–833.
  154. Hadley, C.W.; Clinton, S.K.; Schwartz, S.J. The Consumption of Processed Tomato Products Enhances Plasma Lycopene Concentrations in Association with a Reduced Lipoprotein Sensitivity to Oxidative Damage. J. Nutr. 2003, 133, 727–732.
  155. Ganji, V.; Kafai, M.R. Population Determinants of Serum Lycopene Concentrations in the United States: Data from the Third National Health and Nutrition Examination Survey, 1988–1994. J. Nutr. 2005, 135, 567–572.
  156. Kong, Q.; Yuan, J.; Gao, L.; Liu, P.; Cao, L.; Huang, Y.; Zhao, L.; Lv, H.; Bie, Z. Transcriptional Regulation of Lycopene Metabolism Mediated by Rootstock during the Ripening of Grafted Watermelons. Food Chem. 2017, 214, 406–411.
  157. Hussain, A.; Pu, H.; Sun, D.-W. Measurements of Lycopene Contents in Fruit: A Review of Recent Developments in Conventional and Novel Techniques. Crit. Rev. Food Sci. Nutr. 2019, 59, 758–769.
  158. Mayeaux, M.; Xu, Z.; King, J.M.; Prinyawiwatkul, W. Effects of Cooking Conditions on the Lycopene Content in Tomatoes. J. Food Sci. 2006, 71, C461–C464.
  159. Rodriguez, E.B.; Rodriguez-Amaya, D.B. Lycopene Epoxides and Apo-Lycopenals Formed by Chemical Reactions and Autoxidation in Model Systems and Processed Foods. J. Food Sci. 2009, 74, C674–C682.
  160. Colle, I.; Lemmens, L.; Van Buggenhout, S.; Van Loey, A.; Hendrickx, M. Effect of Thermal Processing on the Degradation, Isomerization, and Bioaccessibility of Lycopene in Tomato Pulp. J. Food Sci. 2010, 75, C753–C759.
  161. Chen, H.; Zhong, Q. Thermal and UV Stability of β-Carotene Dissolved in Peppermint Oil Microemulsified by Sunflower Lecithin and Tween 20 Blend. Food Chem. 2015, 174, 630–636.
  162. Ge, W.; Li, D.; Chen, M.; Wang, X.; Liu, S.; Sun, R. Characterization and Antioxidant Activity of β-Carotene Loaded Chitosan-Graft-Poly(Lactide) Nanomicelles. Carbohydr. Polym. 2015, 117, 169–176.
  163. Honda, M.; Watanabe, Y.; Murakami, K.; Takemura, R.; Fukaya, T.; Wahyudiono; Kanda, H.; Goto, M. Thermal Isomerization Pre-Treatment to Improve Lycopene Extraction from Tomato Pulp. LWT 2017, 86, 69–75.
  164. Hernández-Almanza, A.; Montañez, J.; Martínez, G.; Aguilar-Jiménez, A.; Contreras-Esquivel, J.C.; Aguilar, C.N. Lycopene: Progress in Microbial Production. Trends Food Sci. Technol. 2016, 56, 142–148.
  165. Antonuccio, P.; Micali, A.; Puzzolo, D.; Romeo, C.; Vermiglio, G.; Squadrito, V.; Freni, J.; Pallio, G.; Trichilo, V.; Righi, M.; et al. Nutraceutical Effects of Lycopene in Experimental Varicocele: An “In Vivo” Model to Study Male Infertility. Nutrients 2020, 12, 1536.
  166. Rao, A.V.; Ray, M.R.; Rao, L.G. Lycopene. In Advances in Food and Nutrition Research; Academic Press: Cambridge, MA, USA, 2006; Volume 51, pp. 99–164. ISBN 0120164515.
  167. Re, R.; Fraser, P.D.; Long, M.; Bramley, P.M.; Rice-Evans, C. Isomerization of Lycopene in the Gastric Milieu. Biochem. Biophys. Res. Commun. 2001, 281, 576–581.
  168. Honest, K.N.; Zhang, H.W.; Zhang, L. Lycopene: Isomerization Effects on Bioavailability and Bioactivity Properties. Food Rev. Int. 2011, 27, 248–258.
  169. Anguelova, T.; Warthesen, J. Degradation of Lycopene, α-Carotene, and β-Carotene During Lipid Peroxidation. J. Food Sci. 2000, 65, 71–75.
  170. Liu, D.; Shi, J.; Colina Ibarra, A.; Kakuda, Y.; Jun Xue, S. The Scavenging Capacity and Synergistic Effects of Lycopene, Vitamin E, Vitamin C, and β-Carotene Mixtures on the DPPH Free Radical. LWT Food Sci. Technol. 2008, 41, 1344–1349.
  171. Erdman, J.W.; Ford, N.A.; Lindshield, B.L. Are the Health Attributes of Lycopene Related to Its Antioxidant Function? Arch. Biochem. Biophys. 2009, 483, 229–235.
  172. Yonar, M.E.; Sakin, F. Ameliorative Effect of Lycopene on Antioxidant Status in Cyprinus carpio during Pyrethroid Deltamethrin Exposure. Pestic. Biochem. Physiol. 2011, 99, 226–231.
  173. Takehara, M.; Nishimura, M.; Kuwa, T.; Inoue, Y.; Kitamura, C.; Kumagai, T.; Honda, M. Characterization and Thermal Isomerization of (All-E)-Lycopene. J. Agric. Food Chem. 2014, 62, 264–269.
  174. Srinivasan, M.; Sudheer, A.R.; Pillai, K.R.; Kumar, P.R.; Sudhakaran, P.R.; Menon, V.P. Lycopene as a Natural Protector against γ-Radiation Induced DNA Damage, Lipid Peroxidation and Antioxidant Status in Primary Culture of Isolated Rat Hepatocytes in Vitro. Biochim. Biophys. Acta 2007, 1770, 659–665.
  175. Sy, C.; Gleize, B.; Dangles, O.; Landrier, J.F.; Veyrat, C.C.; Borel, P. Effects of Physicochemical Properties of Carotenoids on Their Bioaccessibility, Intestinal Cell Uptake, and Blood and Tissue Concentrations. Mol. Nutr. Food Res. 2012, 56, 1385–1397.
  176. Suwannalert, P.; Boonsiri, P.; Khampitak, T.; Khampitak, K.; Sriboonlue, P.; Yongvanit, P. The Levels of Lycopene, Alpha-Tocopherol and a Marker of Oxidative Stress in Healthy Northeast Thai Elderly. Asia Pac. J. Clin. Nutr. 2007, 16 (Suppl. 1), 27–30.
  177. Kujawska, M.; Ewertowska, M.; Adamska, T.; Sadowski, C.; Ignatowicz, E.; Jodynis-Liebert, J. Antioxidant Effect of Lycopene-Enriched Tomato Paste on N-Nitrosodiethylamine-Induced Oxidative Stress in Rats. J. Physiol. Biochem. 2014, 70, 981–990.
  178. Aqeel, S.; Naheda, A.; Raza, A.; Khan, K.; Khan, W. Differential Status and Significance of Non-Enzymatic Antioxidants (Reactive Oxygen Species Scavengers) in Malaria and Dengue Patients. Acta Trop. 2019, 195, 127–134.
  179. Sánchez-Villamil, J.P.; Bautista-Niño, P.K.; Serrano, N.C.; Rincon, M.Y.; Garg, N.J. Potential Role of Antioxidants as Adjunctive Therapy in Chagas Disease. Oxid. Med. Cell. Longev. 2020, 2020, 9081813.
  180. Ngouela, S.; Lenta, B.N.; Noungoue, D.T.; Ngoupayo, J.; Boyom, F.F.; Tsamo, E.; Gut, J.; Rosenthal, P.J.; Connolly, J.D. Anti-Plasmodial and Antioxidant Activities of Constituents of the Seed Shells of Symphonia Globulifera Linn F. Phytochemistry 2006, 67, 302–306.
  181. Batista, R.; De Jesus Silva Júnior, A.; De Oliveira, A. Plant-Derived Antimalarial Agents: New Leads and Efficient Phytomedicines. Part II. Non-Alkaloidal Natural Products. Molecules 2009, 14, 3037–3072.
  182. Soh, P.N.; Witkowski, B.; Olagnier, D.; Nicolau, M.L.; Garcia-Alvarez, M.C.; Berry, A.; Benoit-Vical, F. In Vitro and in Vivo Properties of Ellagic Acid in Malaria Treatment. Antimicrob. Agents Chemother. 2009, 53, 1100–1106.
  183. Ferreira, J.F.S.; Luthria, D.L.; Sasaki, T.; Heyerick, A. Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer. Molecules 2010, 15, 3135–3170.
  184. Paddon, C.J.; Westfall, P.J.; Pitera, D.J.; Benjamin, K.; Fisher, K.; McPhee, D.; Leavell, M.D.; Tai, A.; Main, A.; Eng, D.; et al. High-Level Semi-Synthetic Production of the Potent Antimalarial Artemisinin. Nature 2013, 496, 528–532.
  185. Richard, S.A.; Black, R.E.; Caulfield, L.E. Undernutrition as An Underlying Cause of Malaria Morbidity and Mortality in Children Less Than Five Years Old. Am. J. Trop. Med. Hyg. 2004, 71, 55–63.
  186. Akpotuzor, J.O.; Udoh, A.E.; Etukudo, M.H. Total Antioxidant Status, Vitamins A, C and β-Carotene Levels of Children with P. falciparum Infection in University of Calabar Teaching Hospital (UCTH), Calabar. Pakistan J. Nutr. 2007, 6, 485–489.
  187. Varela, E.L.P.; Gomes, A.R.Q.; Santos, A.S.B.; Cruz, J.N.; Carvalho, E.P.; Prazeres, B.A.P.; Dolabela, M.F.; Percário, S. Antiparasitic Effect of Lycopene in Experimental Malaria. AABC, 2022; submitted.
  188. Zeba, A.N.; Sorgho, H.; Rouamba, N.; Zongo, I.; Rouamba, J.; Guiguemdé, R.T.; Hamer, D.H.; Mokhtar, N.; Ouedraogo, J.B. Major Reduction of Malaria Morbidity with Combined Vitamin A and Zinc Supplementation in Young Children in Burkina Faso: A Randomized Double Blind Trial. Nutr. J. 2008, 7, 1–7.
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Subjects: Infectious Diseases; Nutrition & Dietetics
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Everton Luiz Pompeu Varela
,
Antônio Rafael Quadros Gomes
,
Aline da Silva Barbosa dos Santos
,
Eliete Pereira de Carvalho
,
Valdicley Vieira Vale
,
Sandro Percário
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Entry Collection: Biopharmaceuticals Technology
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Update Date: 09 Jan 2023
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