Food safety is related to the national economy and people’s livelihood. Fumonisins are widely found in animal feed, feed raw materials, and human food. This can not only cause economic losses in animal husbandry but can also have carcinogenicity or teratogenicity and can be left in animal meat, eggs, and milk which may enter the human body and pose a serious threat to human health. Although there are many strategies to prevent fumonisins from entering the food chain, the traditional physical and chemical methods of mycotoxin removal have some disadvantages, such as an unstable effect, large nutrient loss, impact on the palatability of feed, and difficulty in mass production. As a safe, efficient, and environmentally friendly detoxification technology, biological detoxification attracts more and more attention from researchers and is gradually becoming an accepted technique. 伏马菌素广泛存在于动物饲料、饲料原料和人类食品中。这不仅会给畜牧业造成经济损失,而且具有致癌性或致畸性,残留在动物肉、蛋、奶中,可能进入人体,对人体健康构成严重威胁。伏马菌素的生物解毒机制主要是通过抗氧化中和氧化应激引起的活性氧,从而降低伏马菌素通过氧化应激介导的作用。生物抗氧化剂包括多酚、甾醇、苯丙酸、脂溶性和水溶性物质、植物精油等抗氧化剂。
1. Introduction一、简介
Mycotoxins霉菌毒素是由子囊菌的许多丝状真菌产生的有毒次级代谢产物 are[ toxic1 secondary]。霉菌毒素污染是一个持续存在的全球性问题,不可避免且不可预测。霉菌毒素的产生受周围环境的影响;即使是良好的生长和储存环境也不能完全阻止霉菌毒素的产生[ metabolites2 produced]。伏马菌素是继黄曲霉毒素后对食品和动物健康构成重大威胁的一组毒素。伏马菌素毒性大,常与黄曲霉毒素毒性同时出现。它们给畜禽养殖业造成巨大的经济损失,威胁人类健康[ by3 many filamentous fungi of ascomycetes [1]. Mycotoxin pollution is a persistent global problem which is inevitable and unpredictable. The production of mycotoxins is affected by the surrounding environment; even a good growth and storage environment cannot completely prevent the production of mycotoxins [2]. Fumonisins are a group of toxins that pose a significant threat to food and animal health after aflatoxins. Fumonisins have high toxicity and often appear together with aflatoxin toxicity. They cause huge economic losses to the livestock and poultry breeding industry and threaten human health [3][4]. Therefore,
several4 ]]。因此,一些研究一直在探索控制和减轻伏马菌素毒性的方法。伏马菌素很容易污染玉米、大米和其他谷物,对以这些谷物为食的几种动物的肝脏和肾脏造成损害,甚至引起肿瘤问题 studies[ have5 been exploring methods to control and alleviate fumonisin toxicity. Fumonisins easily contaminate corn,
rice,6 and]。此外,伏马菌素的毒性与引起人类食管癌和神经管缺损病有关[ other7、8 grains,] causing damage to the liver and kidneys of several animals that feed on these grains and even causing tumor problems [5][6]. In addition, fumonisin toxicity is implicated in causing human esophageal cancer and neural tube defect disease [7][8], thus fumonisins have gradually become a research hotspot after aflatoxin.,因此伏马菌素逐渐成为继黄曲霉毒素之后的研究热点。
Fumonisins伏马菌素是一种水溶性次生代谢产物,主要由轮枝镰刀菌、增殖镰刀菌和其他镰刀菌属物种产生 are[ a9 water-soluble]。它存在于多种基质上,主要存在于玉米等谷物上,也存在于以谷物为原料制造的产品中 secondary[ metabolite5 mainly produced by Fusarium verticillioides, Fusarium proliferatum, and other Fusarium species [9]. It exists on a variety of substrates, mainly on grains such as corn, and can also be found in products manufactured using grains as raw materials [5]. Fumonisins can be divided into four categories: ]。伏马菌素可分为四类:A
, 、B
, C and P, including 28 structural analogues: 、C 和 P,包括 28 种结构类似物:FA
1,、 FA
2,、 FA
3,、 PHFA
3a,、 PHFA
3b,、 HFA
3,、 FAK
1,、 FBK
1,、 FB
1,、 Iso-
FB
1, PHFB
1a,、 PHFB
1b,、 HFB
1,、 FB
2,、 FB
3,、 FB
4,、 FB
5,、 FC
1,、 N-
acetyl乙酰基-FC
1,、 Iso-FC
1,、 N-
acetyl乙酰基-iso-FC
1,、 OH-FC
1,、 N-
acetyl乙酰基-OH-FC
1,、 FC
3,、 FC
4,、 FP
1,、 FP
2,和 and FP
3。值得注意的是,伏马菌素 (Table 1).B Notably, the fumonisin 家族是主要且毒性最强的家族。伏马菌素B
family is the main and most toxic family. Fumonisin B1 (FB
1 )
and fumonisin和伏马菌素 B B2 (FB
2)
are是天然污染玉米的最丰富和毒性最大的变体,占伏马菌素总数的 the most abundant and most toxic variants that naturally contaminate maize, accounting for 70–80% and 15–25% of70-80% 和 15-25% [ the10 total, number11 of fumonisins [10][11].]。
WHO (世界卫生组织(2001
) established a provisional maximum daily tolerable level of fumonisins at 年)将伏马菌素的临时最高每日耐受水平设定为 2 μg/kg-BW
(body(体重),因为其浓度高且毒性高 [ weight),12 owing to its high levels and high toxicity [12]. The European Commission (]。欧盟委员会(2006
and年和 2007
) set the maximum levels of fumonisins for unprocessed maize at 年)将未加工玉米的伏马菌素最高水平设定为 4000 μg/kg
, FB at,人类玉米类食品的 FB 为 1000 μg/kg
for human corn-based foods, ,玉米早餐谷物和零食为 800 μg/kg
for corn breakfast cereals and snacks, and ,以及 200 μg
/kg for corn-based /kg 以玉米为基础的婴儿食品 [ baby13 foods, [13][14].14 The]。国际癌症研究机构 International Agency for Research on Cancer (IARC)
classifies fumonisins into group 2B, which is将伏马菌素分类为 2B 组,由于其有害影响,这可能是人类致癌物 [ a15 possible human carcinogen owing to their harmful effects [15]. Therefore, it is particularly significant to reduce the content and detoxify fumonisins in food.]。因此,降低食品中伏马菌素的含量和解毒作用就显得尤为重要。
Fumonisins伏马菌素易溶于水,热稳定性强,在各种条件下化学性质稳定。因此,将它们从普通谷物加工中去除以满足正常食用标准是一项挑战[ are16 highly]。物理和化学方法不能有效去除谷物中的伏马菌素等有毒物质。研究报告称,生物方法可以有效去除农作物中的伏马菌素。因此,研究广泛探讨了通过生物控制和生物降解来抑制伏马菌素生产菌株的生长和降解[ soluble17 in water and have strong thermal stability,
thus18 they are chemically stable under various conditions. It is therefore challenging to remove them from ordinary grain processing to meet normal edible standards [16]. Physical and chemical methods cannot effectively remove fumonisins and other toxic substances from grains. Studies report that biological methods can effectively remove fumonisins in crops. Therefore, studies have widely explored the inhibition of fumonisin-producing strain growth and degradation of fumonisins through biological control and biodegradation [17][18].]。
2. Polyphenols
2. 多酚
Curcumin姜黄素是从姜科和其他植物的根茎中提取的一种天然多酚类化合物[ is56 a]。值得注意的是,姜黄素通过刺激神经酰胺的从头合成、激活中性鞘磷脂酶和抑制鞘磷脂合酶的活性来增加神经酰胺浓度 natural[ polyphenolic57 compound extracted from the rhizome of Zingiberaceae and other plants.[19]. Notably, curcumin increases ceramide concentration by stimulating de novo synthesis of ceramide, activating neutral sphingomyelinase and inhibiting the activity of sphingomyelin synthase [20]. Lloyd]。劳埃德-
Evans埃文斯等人。观察到姜黄素通过恢复细胞内钙含量来减少 et al. observed that curcumin reduces the intracellular accumulation of So, sphingomyelin, glycosphingolipids, and cholesterol by restoring the intracellular calcium content. These characteristics are the main features of So、鞘磷脂、鞘糖脂和胆固醇的细胞内积累。这些特征是 Niemann-PicktypeC1
disease病的主要特征 [21],[ as well as features for fumonisin poisoning. Feeding chicks with curcumin nanocapsules supplemented with 58],以及伏马菌素中毒的特征。用添加600 mg/kg
fumonisin and 伏马菌素和10 mg/kg
curcumin, showed protecting protective effects to the liver and an antioxidant effect, as well as reducing the level of thiobarbituric acid active substance in ROS and姜黄素的姜黄素纳米胶囊喂养雏鸡,表现出对肝脏的保护作用和抗氧化作用,并降低了ROS中硫代巴比妥酸活性物质的水平,提高了鸡的增重。小鸡与对照组相比 [ improving59 the weight gain of chicks compared with the control group [22]. Moreover,]。此外,姜黄素可减少体外 curcumin reduces PK-15
death的死亡。施用用 50 μM FB 1预处理的姜黄素 in vitro. Administration of curcumin PK-15
cells pretreated with 50 μM FB1 showed an increase in the cell survival rate from 5细胞显示细胞存活率从 53.7%
to提高到 77%
and a decrease in the intracellular ROS content from ,细胞内 ROS 含量从 97.4%
to降低到 75.5%
[23].[ Silymarin60]。水飞蓟素 (SIL)
is als也是一种多酚,其作用与姜黄素相似。So
a polyphenol with a similar effectzmen 等人。报道在用 100 mg/kg FB to1和 that of curcumin1.
Sozmen et al. reported that SIL significantly reduced hepatocyte apoptosis5 mg/kg SIL处理的 BALB/c 小鼠中,SIL 显着降低肝细胞凋亡 ( (p < 0.0001)
and并上调 upregulated the expression of Caspase-8
and和 TNF-α
的表达 (
p < 0.0001)
体内 in[ BALB/c61 mice treated with 100 mg/kg FB1 as well as 1.5 mg/kg SI]。此外,L
in vivo [24]. Furthermore
, Ledur
et al. observed that the administration of 50 μM FB1等人。观察到,对用 2.5 μM SIL to预处理的 PK-15
cells pretreated with 2.5 μM SIL细胞施用 50 μM FB increased the cell1可使细胞存活率从 survival rate from 53.7%
to提高到 89.2%
and decreased the intracellular ROS content from ,并将细胞内 ROS 含量从 97.4%
to降低到 34.2%
[23].[ Moreover,60 ]。此外,Marnewick
et al. reported that tea polyphenols alleviate hepatotoxicity induced by 等人。据报道,茶多酚可减轻 FB
1. 引起的肝毒性。例如,雄性 F
or i
nstance, the administration in male Fischer rats of scher 大鼠在发酵前后给予 250 mg/kg FB
1和 and aqueous extracts of roorooibos (
Aspalathus linearis )
, 、honeybush (
Cyclopia intermedia )
, herbal,、草本茶和绿茶 ( and green and black (Camellia sinensis )
teas before and after fermentation showed a significant increase in the scavenging ability of mouse liver cells to free radicals. In addition, fermented herbal teas and unfermented honeybush significantly reduced liver lipid peroxidation induced by 的水提取物显示出显着的效果。增加小鼠肝细胞对自由基的清除能力。此外,发酵的凉茶和未发酵的蜜树显着降低了 FB
1.诱导的肝脏脂质过氧化。此外,三种茶提取物都不同程度地提高了 Moreover, the three tea extracts improved the activities of CAT, GPx, and GR at varyingCAT、GPx 和 GR 的活性 [ degrees [25]. Chlorogenic acid also has an inhibitory effect on fumonisin-producing strains. Chlorogenic acid is a common dietary polyphenol with significant bioactivity. The inhibition rate of fumonisin-producing strains after administration of chlorogenic acid was up to 62]。绿原酸对产生伏马菌素的菌株也有抑制作用。绿原酸是一种常见的膳食多酚,具有显着的生物活性。给予绿原酸后对伏马菌素产生菌株的抑制率高达70%
[ 63 [26].]。
3. Sterols
3. 甾醇
Hassan et al. explored the protective effect of ginseng extract (PGE) on mice exposed to FB
1, as PGE contains a lot of sterols such as ginsenosides. The findings indicated that PGE reduced fragmentation of DNA in the liver and kidney after the administration of 20 mg/kg-BW of PGE and 100 μg/kg-BW FB
1 to male mice at the same time. Moreover, PGE alleviated LP changes in the liver and kidney, increased GSH level, and upregulated GPx, SOD1, and CAT mRNA expression. In addition, the GPx, SOD1, and CAT mRNA expression levels of mice in the PGE group treated with 20 mg/kg-BW of FB
1 were significantly higher relative to the expression levels of mice in the blank control group
[27][64]. Additionally, Abdel-Wahhab et al. explored the effect of red ginseng on FB
1 toxicity in Sprague-Dawley rats and reported consistent findings
[28][65]. The root extract of
Panax notoginseng has an inhibitory effect on the carcinogenicity of FB
1. Takao et al. administered FB
1 and acetone to female SENCAR mice through a skin smear to stimulate papilloma formation. The treatment group was administered with
Panax notoginseng acetone extract 1 h before each administration of FB
1. The findings showed that 100% of the mice in the control group developed papilloma after 12 weeks of FB
1 and acetone skin smearing, whereas only about 20% and 50% of the mice in the treatment group developed papilloma after 12 and 15 weeks, respectively
[29][66]. Moreover, daily consumption of ginseng may have a preventive or detoxifying effect on fumonisin toxicity.
4. Phenylpropionic Acids
Ferulic acid is a phenyl propionic acid compound derived from Ferula feruloides (Steudel) Korovin and other plants. Ferulic acid at 10–25 mM significantly decreased the growth rate of
Fusarium oxysporum compared with the control group (
p < 0.001). In addition, fumonisin production was inhibited to a certain extent
[30][67]. Ferulic acid can be extracted from cheap agricultural by-products, therefore, the extraction of ferulic acid from low-cost agricultural by-products can be an important source in controlling the production of fumonisins in plants
[31][32][68,69].
5. Vitamins
Vitamin E is an important antioxidant. Pretreatment of mice with 25 µM vitamin E (tocopherol) for 24 h before 18 µM FB
1 treatment significantly reduces FB
1-induced DNA damage and apoptosis
[33][34][70,71]. In addition, vitamin E can be combined with selenium, CoQ10, and L-carnitine to prepare a compound with synergistic effects. In a
previous
study, mice were pretreated with vitamin E (30 IU/kg), selenium (1 mg/kg), CoQ10 (30 mg/kg), and L-L-carnitine (2.8 mg/kg), then intravenously administered with 1.55 mg/kg-BW FB
1. The results indicated that a combination of these antioxidants alleviated DNA damage and increased the activities of aspartate aminotransferase and alanine aminotransferase by 18% and 18%, respectively, compared with the level of mice not exposed to FB
1 [35][33]. Oginni et al. administered juvenile catfish with vitamin E and vitamin C at the same time and observed that the decrease in nutrient content in juvenile catfish induced by FB
1 was improved. Notably, the crude protein content in juvenile catfish was higher compared with that of the FB
1 group (
p < 0.05)
[36][72]. Furthermore, folic acid has a protective effect on cytotoxicity induced by fumonisins. Sadler et al. reported that folic acid reduced the toxic effect of FB
1 on mouse embryos and improved the growth of mouse embryos after culturing embryos with a mixture of 10 mM folic acid and 2 µM FB
1, indicating that folic acid improves the toxic effect of fumonisins, however, the change was not significant
[37][73].
6. Essential Oil
Essential oils are unique aromatic substances extracted from plants, mainly containing alcohols, aldehydes, phenols, acetones, terpenes, and other volatile secondary metabolites synthesized by plants
[38][39][74,75]. Several types of essential oils such as
Litsea cubeba, cinnamon, and ginger have been reported, and most have an inhibitory effect on bacterial growth. Pante et al. conducted an in vitro experiment and reported that
Litsea cubeba essential oil inhibited mycelial development of
Furium verticillioides and synthesis of FB
1 and FB
2. The minimum inhibitory concentration of
Fusarium verticillioides was 125 µg/mL and the inhibitory effect was dose dependent. The antioxidant effect of
Litsea cubeba essential oil was evaluated by DPPH and ABTS methods, showing excellent antioxidant activity
[40][76]. Bomfim et al. reported that
Rosmarinus officinalis L. essential oil (REO) had a similar effect. Administration of 300 µg/mL REO caused significant morphological changes such as bacterial cell wall rupture and cell content flow out in a dose-dependent manner
[41][77]. In addition,
Zingiber officinale essential oil (GEO) inhibits the growth of fumonisin-producing bacteria and fumonisin production. Notably, administration of 2000 µg/mL GEO and 4000 µg/mL GEO significantly inhibits the production of FB
1 and FB
2. The inhibition rates of ergosterol biosynthesis after administration of 4000 µg/mL and 5000 µg/mL GEO were 57% and 100%, respectively
[42][78]. Ergosterol modulates the activity of several membrane binding enzymes
[43][79], and the reduction of ergosterol activity could result in membrane synthesis disorders, thus exhibiting a bacteriostatic effect. Castro et al. reported similar results with minimum inhibitory concentrations of
Cinnamomum zeylanicum and
Cymbopogon martinii essential oils to
Fusarium verticillioides at 250, 250, and 500 µg/mL, respectively
[44][80]. Plant essential oils inhibit the growth of fumonisin-producing bacteria and fumonisin production, as well as reduce or prevent toxicity caused by fumonisins. Essential oils have a strong smell and react with some drugs, thus, embedding technology is commonly used to embed essential oils. Cinnamon essential oil embedded with whey protein effectively improved the serum levels of ALT, AST, ALP, Urea, and Uric acid, and restored the normal levels in male Sprague-Dawley male rats treated with 100 mg/kg-BW FB
1. Furthermore, testosterone levels in rats were restored to normal values thus reducing reproductive toxicity. Lipid peroxidation and tumor marker TNF-α in liver and kidney tissues were improved to some extent but were not restored to normal levels
[38][74]. Studies report that the cinnamon extract glycerol monolaurate (GML) has similar effects. The levels of serum triglyceride, globulin, cholesterol, liver lipid peroxidation, SOD, and serum reactive oxygen species were restored to normal or below normal levels after chicks were fed with 400 µg/kg fumonisins and GML coated with 8 mg/kg nanomaterials. However, the body weight of chicks was not improved indicating that GML does not reduce the oxidative stress caused by fumonisins to a minimum. However, it alleviates oxidative stress caused by fumonisins and enhances the activity of glutathione S-transferase which is the enzyme responsible for liver detoxification
[45][81].
7. Other Antioxidants
In addition to the above-mentioned antioxidants, several other types of antioxidants have been reported in previous studies. Domijan et al. reported that sodium copper chlorophyllin (CHL) had a protective effect on FB
1-induced cell and DNA damage after administration of 100 µg/mL (CHL) in combination with 20 µg/mL of FB
1. Oxidative stress is the main cause of DNA damage caused by FB
1, thus CHL indirectly prevented FB
1-induced cell death, DNA damage, and possible carcinogenesis by preventing oxidative stress
[46][82]. Zhao et al. conducted a study whereby indole glucosinolates (IGS) were infiltrated into wild-type Col-0 plants followed by a 10 µM FB
1 solution into the wild-type IGS plants and compared the results with the administration of only the FB
1 solution. The findings showed that IGS inhibited FB
1-induced apoptosis. IGS decomposition products produced through the action of β-glucosinolase effectively reduce the accumulation of ROS, increase the activity of antioxidant enzymes, and improve ROS scavenging ability, thus reducing FB
1-induced oxidative stress and apoptosis
[47][83]. CHL and IGS are widely distributed in green leafy vegetables, thus eating more green leafy vegetables may have a preventive effect on fumonisins toxicity.
In addition to single-component antioxidants, several compound antioxidants have been reported. Hassan et al. observed that all biochemical and cytogenetic test parameters and histological images of liver tissue were significantly improved after feeding mice with an ethanol extract of
Aquilegia vulgaris L. at 10 mg/kg-BW and 200 mg/kg voronisin
[48][84]. Gbore et al. reported that the food intake of female rabbits approached the normal level after administration of Moringa leaf meal (MLM) in combination with FB
1 and the effect of MLM was dose dependent. The antioxidant effect of MLM improved the adverse effects of FB
1 on nutrient utilization and growth performance of female rabbits. Notably, MLM is a cheaper alternative compared with commercial antioxidants. MLM can be used as an antidote in traditional feed to reduce the harmful effects of FB
1 on domestic animal production
[49][85].
Moreover,此外,昆虫产品具有抗氧化作用。一些蜜蜂产品是天然抗氧化剂的潜在来源,可以抵消由各种疾病引起的氧化应激的影响 insect[ products86 have antioxidant effects. Several honeybee products are potential sources of natural antioxidants and can counteract the effects of oxidative stress caused by various diseases [50]. ]。蜂王浆(R
oyal jelly (RJ
) contains)含有多种生物活性物质和酚类化合物,主要包括黄酮类和茴香酸,具有抗氧化活性。与单独喂食 FB several bioactive substances and phenolic1的小鼠相比,当雄性 compounds, mainly comprising flavonoids and fenac, and has antioxidant activities. Liver and kidney indexes were significantly improved when male Sprague-Dawley
rats were administered with a combination of 大鼠联合 200 mg/kg
fumonisins and 伏马菌素和 150 mg/kg-BW RJ
compared with the levels in mice fed with FB1 alone. Liver and kidney indexes were also restored to normal levels, indicating that 给药时,肝脏和肾脏指数显着改善。肝肾指标也恢复到正常水平,说明RJ
对伏马菌素毒性有保护作用。值得注意的是,保护作用是剂量依赖性的 has[ a87 protective effect on fumonisin toxicity. Notably, the protective effect was dose dependent [51].
]。