Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Adam Wichniak
 + 1665 word(s) 1665 2021-08-18 04:11:50 |
2 h
Camila Xu
 + 165 word(s) 1830 2021-08-25 10:34:18 | |
3 h
Camila Xu
 + 165 word(s) 1830 2021-08-25 10:34:57 | |
4 h
Camila Xu
 + 165 word(s) 1830 2021-08-25 10:35:25 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Wichniak, A. Melatonin in Disease and Health. Encyclopedia. Available online: https://encyclopedia.pub/entry/13298 (accessed on 20 April 2024).
Wichniak A. Melatonin in Disease and Health. Encyclopedia. Available at: https://encyclopedia.pub/entry/13298. Accessed April 20, 2024.
Wichniak, Adam. "Melatonin in Disease and Health" Encyclopedia, https://encyclopedia.pub/entry/13298 (accessed April 20, 2024).
Wichniak, A. (2021, August 18). Melatonin in Disease and Health. In Encyclopedia. https://encyclopedia.pub/entry/13298
Wichniak, Adam. "Melatonin in Disease and Health." Encyclopedia. Web. 18 August, 2021.
Melatonin in Disease and Health
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms22168623

Melatonin is a derivative of tryptophan, synthesized mainly in the pineal gland. Its synthesis is characterized by a regular circadian rhythm, with a peak concentration in plasma reached in the night hours. The intensity of melatonin production is related to exposure to light, with an increase of its synthesis in the dark part of the day.

COVID-19 melatonin physiological effects disease progression treatment

1. Introduction

The pandemic caused by the coronavirus disease 2019 (COVID-19) increased the awareness of several health-related factors that reduce the risk of infection and decrease the likelihood of a severe course of the disease. A good sleep quality is identified among those factors, as sleep plays numerous essential functions, promoting health, regenerative, and immunomodulatory processes. Thus, a poor sleep quality impairs the immune system and increases the organism’s susceptibility to infection [1]. The empirical evidence shows a link between a short sleep duration (below 6 h) before viral exposure and increased (over four times) susceptibility to developing a common cold after the administration of nasal drops containing the rhinovirus [2]. A short sleep duration was demonstrated to negatively affect antibody responses to influenza and hepatitis B vaccinations [3][4]. Taking into account that a good sleep quality also plays a crucial role in the regulation of emotions [5], the clinical data strongly support the role of educational activities and interventions aimed at improving sleep quality as essential strategies to protect society against COVID-19 and help people to cope with the stress related to the COVID-19 pandemic.

Experts in cognitive-behavioral therapy proposed several operationalized behavioral interventions to counteract the deterioration of sleep quality related to the COVID-19 pandemic. Psychological treatment aims to help people cope with the stressors associated with the COVID-19 pandemic, promote sleep regulation, focusing on homeostatic sleep drive and circadian sleep rhythm, and change negative cognitions related to the bed and the bedroom from not sleeping into reformulated cognitions linked with good quality sleep. These interventions address, first of all, the negative sleep-related consequences of home confinement due to the COVID-19 pandemic, reducing physical activity and social interactions and disturbing sleep rhythm [6]. However, despite their efficacy and general recommendations that hypnotics should be avoided, because their effectiveness is questionable and can have some side effects if taken long-term [7][6], many patients still require pharmacological treatment. One of the drugs frequently used as an alternative to hypnotics to treat sleep disturbances is melatonin, which is widely available in many countries as an over-the-counter medicine.

The high safety of melatonin treatment, the essential role of social rhythm changes, negatively influencing circadian sleep rhythm and causing deterioration of sleep quality during COVID-19 confinement, the lack of dependence risk of melatonin treatment, and the fact that melatonin has no adverse effect on respiratory drive have caused researchers and clinicians to consider melatonin not only as a recommended treatment for sleep disturbances, but also as an adjuvant treatment for COVID-19.

2. COVID-19 and Potential Clinical Applications of Melatonin

COVID-19 is a disease resulting from an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The most frequent symptoms include fever, fatigue, anosmia with ageusia, coughing, and dyspnea, which usually occur around 3–5 days from the initial infection [8]. The spectrum of the disease is broad, ranging from true asymptomatic or paucisymptomatic infection to fatal disease complications [9]. The disease affects not only the respiratory system, but also the nervous, digestive, and circulatory systems. It may also affect the kidneys, bone marrow, and other organs [10][11]. However, respiratory tract involvement is the most common cause of death among COVID-19 patients. The mechanism of death is almost always associated with acute respiratory failure and, finally, acute respiratory distress syndrome (ARDS) [12].

To date, no effective drug against SARS-CoV-2 has been approved for human use. However, evidence-based medicine permits us develop treatment guidelines [13]. The optimal strategies based on early recognition and intervention seem to be the best option [14].

The search for new drugs and the study of the properties of the already known molecules in the fight against the COVID-19 pandemic is the subject of intensive research. While no empirical data supported by clinical trial results are available on the usefulness of melatonin in the treatment of COVID-19, the general knowledge on melatonin pharmacodynamics may facilitate its hypothesized use in the treatment of COVID-19 and promote clinical research [15]. The effects of melatonin in COVID-19 may include both the preclinical period, the acute phase of the disease, acute phase complications, and late complications of COVID-19 [16][17].

Particular attention should be paid to the possibility of using melatonin in connection with vaccination [18]. The use of melatonin in the period before falling ill could also potentially reduce the severity of the disease and increase the percentage of people who are asymptomatic and suffer a mildly advanced disease. Furthermore, the effects of melatonin may be of particular importance in people with COVID-19 lung involvement. The protective effects of melatonin on lung injury have already been reviewed [19]. Notably, the concepts of melatonin’s action are based not only on its sleep-regulating effect, but also on the described anti-inflammatory, antioxidant, and immunomodulatory properties ( Table 1 ).

Table 1. Potential effects of melatonin on the course of COVID-19 (modified from: [17][19][20][21]).

COVID-19 Phase Effect of Melatonin Treatment Recommended Dose
Prophylaxis Circadian sleep–wake rhythm disorder treatment 0.5–5 mg
Insomnia treatment
Adjuvant to anti-SARS-CoV-2 vaccines		 2–5 mg 1
0.5–2 mg 2
Early infection phase/mild clinical symptoms Improvement of sleep quality
Inhibition of viral invasion
Free oxygen species scavenging
Cytokine suppression		 2–12 mg 3
Pulmonary phase/severe clinical symptoms Improvement of sleep quality
Anti-inflammatory effects
Reduction of “cytokine-storm”
Protection of lungs and tissues from oxidative injury
Risk reduction of ventilator-induced lung injury		 2–12 mg 3,4
Post-infection period Improvement of sleep quality
Stabilization of the disrupted circadian sleep rhythm
Antioxidant properties
Reduction of post-covid pulmonary fibrosis		 0.5–5 mg
1 Preferred prolonged-release form [22]. 2 high doses should be avoided, as they may decrease the immune response [18]. 3 The optimal dose is unknown due to a lack of randomized clinical trials. 4 Doses as high as 400 mg per day have also been suggested [20].

3. Physiological Effects of Melatonin Inhibiting COVID-19 Progression

Apart from its crucial function in sustaining sleep–wake rhythm, melatonin is suggested to play a role in other physiological and pathological processes, although whether this is a direct effect of this neurohormone or indirect consequence of a melatonin-driven fluctuation in the diurnal activity of the organism is still debated. Nevertheless, a significant role of melatonin is postulated, for instance, in neurodegenerative processes [23], metabolism control [24], cardiovascular disorders [25], and (which has a special meaning in the context of this review) in inflammatory diseases [26]. The last connection is additionally underlined by the fact that melatonin is produced by cells of the immune system (mononuclear cells, lymphocytes, and macrophages), stimulated by bacterial antigens [27]. Therefore, it is widely postulated that melatonin possesses anti-inflammatory potential, which may be beneficial in bacterial or viral infections.

There is a line of evidence proving that melatonin may exert anti-inflammatory action, which could hypothetically be useful in the treatment of inflammation evoked by SARS-CoV-2 infection. In this context, the following features of melatonin have specific significance: interaction with the renin-angiotensin system, suppression of proinflammatory cytokines, and antioxidant properties.

The abovementioned finding leads to the hypothesis that reducing the RAS activity, with a lower expression of ACE2 on the cell’s membrane, may lower the virus’s potential to invade the cell. The antagonism between melatonin and RAS was described previously, and the available clinical observations allowed researchers to coin the term, “angiotensin–melatonin axis” [28]. On the sub-cellular level, it was discovered that the surface expression of ACE2 is regulated by calmodulin [29]. Melatonin can bind calmodulin and inhibit its action [30][31]. Therefore, it is plausible that melatonin, through the inhibition of calmodulin, may reduce the expression of ACE2 and limit viral invasion, although this was not proven clinically.

All the abovementioned anti-inflammatory features of melatonin made plausible the hypothesis that it has a therapeutic role in generalized inflammation and sepsis. Indeed, in a series of experiments performed on animal models of sepsis, melatonin was proven to reduce the inflammatory response and protect tissues from oxidative injury [32][33][34]. The literature review by Biancatelli et al. [35] concluded with the suggestion that melatonin can be used in patients with severe sepsis and septic shock, albeit while emphasizing the scarce clinical evidence. So far, it was proven in an ex vivo study of blood taken from human volunteers and treated with bacterial lipopolysaccharides that melatonin causes a reduction of oxidative stress and the proinflammatory activity of cytokines [36]. Certainly, these data are not sufficient to include melatonin in the antiseptic or anti-inflammatory armamentarium, though it opens a promising area of clinical studies ( Table 2 ).

Table 2. Current data on the physiological effects of melatonin, which may be beneficial in bacterial or viral infections.

In Vitro Studies Animal Models Human Studies
Inhibition of calmodulin [30] Regulation of anti/proinflammatory cytokines balance [32] Inhibition of IL-6, IL-1, TNF-alpha [37]
Inhibition of metalloproteinases [38] Restoration of ATP production [39] Reduction of the concentration of IL-1 beta [40]
Reduction of the production of IL-8 [41] Organ protection [34] Reduction of lipid peroxidation [42]

4. Protective Role of Melatonin in Lung Diseases

The fatal consequence of SARS-CoV-2 infection is pneumonia, resulting in respiratory insufficiency, and probably the most prominent long-term effect of COVID-19 is disability resulting from an injury of the lungs. Therefore, it is noteworthy that melatonin in animal models appears to be a therapeutic/protective agent in acute and chronic pulmonary diseases.

From a clinical point of view, the crucial area for melatonin use in the treatment of severe COVID-19 is related to its action in preventing diffuse alveolar damage (DAD). DAD is considered the histological hallmark for the acute phase of acute respiratory distress syndrome (ARDS) [43]. Numerous experimental studies in animal models have shown a beneficial effect of melatonin on lung tissue [19]. It was shown that melatonin improved the histopathology of pulmonary contusion and distant organs. Ozdinc et al. [44] found that in rats treated with melatonin, histopathological changes resulting from pulmonary contusion were less severe than in non-treated animals. The authors suggested that this is the effect of the antioxidant properties of the neurohormone [44]. Moreover, melatonin reduces leukocyte and macrophage infiltration, interstitial hemorrhages, epithelial desquamation in bronchioles and alveoli, and an intra alveolar edema [45].

The other aspect is the ability of melatonin to decrease lung ischemia/reperfusion injury (LIRI). Chiu et al. [46] revealed that melatonin significantly diminished pulmonary microvascular permeability and attenuated the lipid peroxidation in the lungs. In fish, melatonin significantly inhibited the NF-kB expression and downregulated the activity of nuclear factor-erythroid-2–related factor 2 synthesis in hepatic ischemia/ reperfusion-induced lung injury [47].

Moreover, melatonin was proven to be helpful in post-radiation lung fibrosis [48]. It was also shown to inhibit apoptosis and reduce inflammation in animal models of chronic obstructive pulmonary disease (COPD) [49][50]. Melatonin also attenuates fibrotic processes in COPD [51]. Hosseinzadeh recently published a review of the evidence for a possible protective role of melatonin in idiopathic pulmonary fibrosis [52]. It was also shown that melatonin exerts a beneficial effect in experimental models of asthma by remodeling airways [53] and suppressing inflammation [54]. All of the abovementioned discoveries were recently described in animal models. Therefore, they cannot be directly translated to human medicine. Nevertheless, they are sufficient to warrant the proposal of melatonin as a candidate “pneumo-protective” drug in viral infections.

References

  1. Ibarra-Coronado, E.G.; Pantaleón-Martínez, A.M.; Velazquéz-Moctezuma, J.; Prospéro-García, O.; Méndez-Díaz, M.; Pérez-Tapia, M.; Pavón, L.; Morales-Montor, J. The Bidirectional Relationship between Sleep and Immunity against Infections. J. Immunol. Res. 2015, 2015, 678164.
  2. Prather, A.A.; Janicki-Deverts, D.; Hall, M.H.; Cohen, S. Behaviorally Assessed Sleep and Susceptibility to the Common Cold. Sleep 2015, 38, 1353–1359.
  3. Prather, A.A.; Hall, M.; Fury, J.M.; Ross, D.C.; Muldoon, M.F.; Cohen, S.; Marsland, A.L. Sleep and Antibody Response to Hepatitis B Vaccination. Sleep 2012, 35, 1063–1069.
  4. Prather, A.A.; Pressman, S.D.; Miller, G.E.; Cohen, S. Temporal Links between Self-Reported Sleep and Antibody Responses to the Influenza Vaccine. Int. J. Behav. Med. 2021, 28, 151–158.
  5. Vandekerckhove, M.; Wang, Y.-L. Emotion, Emotion Regulation and Sleep: An Intimate Relationship. AIMS Neurosci. 2018, 5, 1–17.
  6. Altena, E.; Baglioni, C.; Espie, C.A.; Ellis, J.; Gavriloff, D.; Holzinger, B.; Schlarb, A.; Frase, L.; Jernelöv, S.; Riemann, D. Dealing with Sleep Problems during Home Confinement Due to the COVID-19 Outbreak: Practical Recommendations from a Task Force of the European CBT-I Academy. J. Sleep Res. 2020.
  7. Riemann, D.; Baglioni, C.; Bassetti, C.; Bjorvatn, B.; Dolenc Groselj, L.; Ellis, J.G.; Espie, C.A.; Garcia-Borreguero, D.; Gjerstad, M.; Gonçalves, M.; et al. European Guideline for the Diagnosis and Treatment of Insomnia. J. Sleep Res. 2017, 26, 675–700.
  8. Guan, W.-J.; Ni, Z.-Y.; Hu, Y.; Liang, W.-H.; Ou, C.-Q.; He, J.-X.; Liu, L.; Shan, H.; Lei, C.-L.; Hui, D.S.C.; et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708–1720.
  9. Mason, R.J. Pathogenesis of COVID-19 from a Cell Biology Perspective. Eur. Respir. J. 2020.
  10. AlSamman, M.; Caggiula, A.; Ganguli, S.; Misak, M.; Pourmand, A. Non-Respiratory Presentations of COVID-19, a Clinical Review. Am. J. Emerg. Med. 2020, 38, 2444–2454.
  11. Polak, S.B.; Van Gool, I.C.; Cohen, D.; von der Thüsen, J.H.; van Paassen, J. A Systematic Review of Pathological Findings in COVID-19: A Pathophysiological Timeline and Possible Mechanisms of Disease Progression. Mod. Pathol. 2020, 33, 2128–2138.
  12. Wang, Y.; Lu, X.; Li, Y.; Chen, H.; Chen, T.; Su, N.; Huang, F.; Zhou, J.; Zhang, B.; Yan, F.; et al. Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. Am. J. Respir. Crit. Care Med. 2020, 1430–1434.
  13. Chalmers, J.D.; Crichton, M.L.; Goeminne, P.C.; Cao, B.; Humbert, M.; Shteinberg, M.; Antoniou, K.M.; Ulrik, C.S.; Parks, H.; Wang, C.; et al. Management of Hospitalized Adults with Coronavirus Disease 2019 (COVID-19): A European Respiratory Society Living Guideline. Eur. Respir. J. 2021, 57.
  14. Sun, Q.; Qiu, H.; Huang, M.; Yang, Y. Lower Mortality of COVID-19 by Early Recognition and Intervention: Experience from Jiangsu Province. Ann. Intensive Care 2020, 33.
  15. Kleszczyński, K.; Slominski, A.T.; Steinbrink, K.; Reiter, R.J. Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed. Nutrients 2020, 12, 2561.
  16. Cardinali, D.P.; Brown, G.M.; Pandi-Perumal, S.R. Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients? Diseases 2020, 8, 44.
  17. Shneider, A.; Kudriavtsev, A.; Vakhrusheva, A. Can Melatonin Reduce the Severity of COVID-19 Pandemic? Int. Rev. Immunol. 2020, 39, 153–162.
  18. Cardinali, D.P.; Brown, G.M.; Pandi-Perumal, S.R. An Urgent Proposal for the Immediate Use of Melatonin as an Adjuvant to Anti- SARS-CoV-2 Vaccination. Melatonin Res. 2021, 4, 206–212.
  19. Wang, W.; Gao, J. Effects of Melatonin on Protecting against Lung Injury (Review). Exp. Ther. Med. 2021, 21, 228.
  20. Reiter, R.J.; Abreu-Gonzalez, P.; Marik, P.E.; Dominguez-Rodriguez, A. Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19. Front. Med. 2020, 7, 226.
  21. Lewandowska, K.; Małkiewicz, M.A.; Siemiński, M.; Cubała, W.J.; Winklewski, P.J.; Mędrzycka-Dąbrowska, W.A. The Role of Melatonin and Melatonin Receptor Agonist in the Prevention of Sleep Disturbances and Delirium in Intensive Care Unit—A Clinical Review. Sleep Med. 2020, 69, 127–134.
  22. Wade, A.G.; Crawford, G.; Ford, I.; McConnachie, A.; Nir, T.; Laudon, M.; Zisapel, N. Prolonged Release Melatonin in the Treatment of Primary Insomnia: Evaluation of the Age Cut-off for Short- and Long-Term Response. Curr. Med. Res. Opin. 2011, 27, 87–98.
  23. Mihardja, M.; Roy, J.; Wong, K.Y.; Aquili, L.; Heng, B.C.; Chan, Y.S.; Fung, M.L.; Lim, L.W. Therapeutic Potential of Neurogenesis and Melatonin Regulation in Alzheimer’s Disease. Ann. N. Y. Acad. Sci. 2020, 43–62.
  24. Behn, C.; De Gregorio, N. Melatonin Relations with Energy Metabolism as Possibly Involved in Fatal Mountain Road Traffic Accidents. Int. J. Mol. Sci. 2020, 21, 2184.
  25. Otamas, A.; Grant, P.J.; Ajjan, R.A. Diabetes and Atherothrombosis: The Circadian Rhythm and Role of Melatonin in Vascular Protection. Diabetes Vasc. Dis. Res. 2020.
  26. MacDonald, I.J.; Huang, C.C.; Liu, S.C.; Tang, C.H. Reconsidering the Role of Melatonin in Rheumatoid Arthritis. Int. J. Mol. Sci. 2020, 21, 2877.
  27. Pereira, Q.L.C.; de Castro Pernet Hara, C.; Fernandes, R.T.S.; Fagundes, D.L.G.; do Carmo França-Botelho, A.; Gomes, M.A.; França, E.L.; Honorio-França, A.C. Human Colostrum Action against Giardia Lamblia Infection Influenced by Hormones and Advanced Maternal Age. Parasitol. Res. 2018, 117, 1783–1791.
  28. Campos, L.A.; Cipolla-Neto, J.; Amaral, F.G.; Michelini, L.C.; Bader, M.; Baltatu, O.C. The Angiotensin-Melatonin Axis. Int. J. Hypertens. 2013, 2013, 521783.
  29. Lambert, D.W.; Clarke, N.E.; Hooper, N.M.; Turner, A.J. Calmodulin Interacts with Angiotensin-Converting Enzyme-2 (ACE2) and Inhibits Shedding of Its Ectodomain. FEBS Lett. 2008, 582, 385–390.
  30. Benítez-King, G.; Ríos, A.; Martínez, A.; Antón-Tay, F. In vitro Inhibition of Ca2+/Calmodulin-Dependent Kinase II Activity by Melatonin. Biochim. Biophys. Acta 1996, 1290, 191–196.
  31. Romero, M.P.; García-Pergañeda, A.; Guerrero, J.M.; Osuna, C. Membrane-Bound Calmodulin in Xenopus Laevis Oocytes as a Novel Binding Site for Melatonin. FASEB J. 1998, 12, 1401–1408.
  32. Carrillo-Vico, A.; Lardone, P.J.; Naji, L.; Fernández-Santos, J.M.; Martín-Lacave, I.; Guerrero, J.M.; Calvo, J.R. Beneficial Pleiotropic Actions of Melatonin in an Experimental Model of Septic Shock in Mice: Regulation of pro-/Anti-Inflammatory Cytokine Network, Protection against Oxidative Damage and Anti-Apoptotic Effects. J. Pineal Res. 2005, 39, 400–408.
  33. Yavuz, T.; Kaya, D.; Behçet, M.; Ozturk, E.; Yavuz, O. Effects of Melatonin on Candida Sepsis in an Experimental Rat Model. Adv. Ther. 2007, 24, 91–100.
  34. Chen, J.; Xia, H.; Zhang, L.; Zhang, H.; Wang, D.; Tao, X. Protective Effects of Melatonin on Sepsis-Induced Liver Injury and Dysregulation of Gluconeogenesis in Rats through Activating SIRT1/STAT3 Pathway. Biomed. Pharmacother. 2019, 117, 109150.
  35. Biancatelli, R.M.L.C.; Berrill, M.; Mohammed, Y.H.; Marik, P.E. Melatonin for the Treatment of Sepsis: The Scientific Rationale. J. Thorac. Dis. 2020, S54–S65.
  36. Galley, H.F.; Lowes, D.A.; Allen, L.; Cameron, G.; Aucott, L.S.; Webster, N.R. Melatonin as a Potential Therapy for Sepsis: A Phase I Dose Escalation Study and an Ex Vivo Whole Blood Model under Conditions of Sepsis. J. Pineal Res. 2014, 56, 427–438.
  37. Hameed, E.N.; Hadi Al Tukmagi, H.F.; Allami, H.C.A. Melatonin Improves Erythropoietin Hyporesponsiveness via Suppression of Inflammation. Rev. Recent Clin. Trials 2019, 14, 203–208.
  38. Qin, W.; Lu, W.; Li, H.; Yuan, X.; Li, B.; Zhang, Q.; Xiu, R. Melatonin Inhibits IL1β-Induced MMP9 Expression and Activity in Human Umbilical Vein Endothelial Cells by Suppressing NF-ΚB Activation. J. Endocrinol. 2012, 214, 145–153.
  39. López, L.C.; Escames, G.; Ortiz, F.; Ros, E.; Acuña-Castroviejo, D. Melatonin Restores the Mitochondrial Production of ATP in Septic Mice. Neuro Endocrinol. Lett. 2006, 27, 623–630.
  40. Alamili, M.; Bendtzen, K.; Lykkesfeldt, J.; Rosenberg, J.; Gögenur, I. Melatonin Suppresses Markers of Inflammation and Oxidative Damage in a Human Daytime Endotoxemia Model. J. Crit. Care 2014, 29, 184.e9–184.e13.
  41. Kim, G.-D.; Lee, S.E.; Kim, T.-H.; Jin, Y.-H.; Park, Y.S.; Park, C.-S. Melatonin Suppresses Acrolein-Induced IL-8 Production in Human Pulmonary Fibroblasts. J. Pineal Res. 2012, 52, 356–364.
  42. Gitto, E.; Karbownik, M.; Reiter, R.J.; Tan, D.X.; Cuzzocrea, S.; Chiurazzi, P.; Cordaro, S.; Corona, G.; Trimarchi, G.; Barberi, I. Effects of Melatonin Treatment in Septic Newborns. Pediatr. Res. 2001, 50, 756–760.
  43. Cardinal-Fernández, P.; Lorente, J.A.; Ballén-Barragán, A.; Matute-Bello, G. Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship. Ann. Am. Thorac. Soc. 2017, 14, 844–850.
  44. Ozdinc, S.; Oz, G.; Ozdemir, C.; Kilic, I.; Karakaya, Z.; Bal, A.; Koken, T.; Solak, O. Melatonin: Is It an Effective Antioxidant for Pulmonary Contusion? J. Surg. Res. 2016, 204, 445–451.
  45. Taslidere, E.; Esrefoglu, M.; Elbe, H.; Cetin, A.; Ates, B. Protective Effects of Melatonin and Quercetin on Experimental Lung Injury Induced by Carbon Tetrachloride in Rats. Exp. Lung Res. 2014, 40, 59–65.
  46. Chiu, M.-H.; Su, C.-L.; Chen, C.-F.; Chen, K.-H.; Wang, D.; Wang, J.-J. Protective Effect of Melatonin on Liver Ischemia-Reperfusion Induced Pulmonary Microvascular Injury in Rats. Transplant. Proc. 2012, 44, 962–965.
  47. Esteban, M.Á.; Cuesta, A.; Chaves-Pozo, E.; Meseguer, J. Influence of Melatonin on the Immune System of Fish: A Review. Int. J. Mol. Sci. 2013, 14, 7979–7999.
  48. Farhood, B.; Aliasgharzadeh, A.; Amini, P.; Rezaeyan, A.; Tavassoli, A.; Motevaseli, E.; Shabeeb, D.; Musa, A.E.; Najafi, M. Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study. Medicina 2019, 55, 417.
  49. He, B.; Zhang, W.; Qiao, J.; Peng, Z.; Chai, X. Melatonin Protects against COPD by Attenuating Apoptosis and Endoplasmic Reticulum Stress via Upregulating SIRT1 Expression in Rats. Can. J. Physiol. Pharmacol. 2019, 97, 386–391.
  50. Peng, Z.; Zhang, W.; Qiao, J.; He, B. Melatonin Attenuates Airway Inflammation via SIRT1 Dependent Inhibition of NLRP3 Inflammasome and IL-1β in Rats with COPD. Int. Immunopharmacol. 2018, 62, 23–28.
  51. Shin, N.-R.; Park, J.-W.; Lee, I.-C.; Ko, J.-W.; Park, S.-H.; Kim, J.-S.; Kim, J.-C.; Ahn, K.-S.; Shin, I.-S. Melatonin Suppresses Fibrotic Responses Induced by Cigarette Smoke via Downregulation of TGF-Β1. Oncotarget 2017, 8, 95692–95703.
  52. Hosseinzadeh, A.; Javad-Moosavi, S.A.; Reiter, R.J.; Hemati, K.; Ghaznavi, H.; Mehrzadi, S. Idiopathic Pulmonary Fibrosis (IPF) Signaling Pathways and Protective Roles of Melatonin. Life Sci. 2018, 201, 17–29.
  53. Yu, Q.; Yu, X.; Zhong, X.; Ma, Y.; Wu, Y.; Bian, T.; Huang, M.; Zeng, X. Melatonin Modulates Airway Smooth Muscle Cell Phenotype by Targeting the STAT3/Akt/GSK-3β Pathway in Experimental Asthma. Cell Tissue Res. 2020, 380, 129–142.
  54. Shin, I.-S.; Park, J.-W.; Shin, N.-R.; Jeon, C.-M.; Kwon, O.-K.; Kim, J.-S.; Kim, J.-C.; Oh, S.-R.; Ahn, K.-S. Melatonin Reduces Airway Inflammation in Ovalbumin-Induced Asthma. Immunobiology 2014, 219, 901–908.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Respiratory System
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Adam Wichniak
View Times: 634
Revisions: 4 times (View History)
Update Date: 25 Aug 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback