Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, mainly by Aspergillus flavus and Aspergillus parasiticus. Aflatoxins, especially aflatoxin B1 (AFB1), are very potent carcinogens in many species, including humans, birds, swine, fish, and rodents. The oxidative stress caused by AFB1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA, protein and lipid damages, which lead to tumorigenesis. This review presents an overview on aflatoxins and oxidative stress, with an emphasis on the protective role of the antioxidants.

Overview on aflatoxins and oxidative stress

Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone's intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin's influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.

Hepatoprotective actions of melatonin: possible mediation by melatonin receptors.

Physicians are increasingly being asked to diagnose and treat people made ill by exposure to water-damaged environments, mold, and mycotoxins. In addition to avoidance of further exposure to these environments and to items contaminated by these environments, a number of approaches have been used to help persons affected by exposure to restore their health. Illness results from a combination of factors present in water-damaged indoor environments including, mold spores and hyphal fragments, mycotoxins, bacteria, bacterial endotoxins, and cell wall components as well as other factors. Mechanisms of illness include inflammation, oxidative stress, toxicity, infection, allergy, and irritant effects of exposure. This paper reviews the scientific literature as it relates to commonly used treatments such as glutathione, antioxidants, antifungals, and sequestering agents such as Cholestyramine, charcoal, clay and chlorella, antioxidants, probiotics, and induced sweating.

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A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins

The effects of evening primrose oil on lipid peroxidation induced by subacute aflatoxin exposure in mice.

Aflatoxin B1 (AFB1) is a potent immunosuppressive agent in endotherms, which can be related to the up-regulated apoptosis of immune organs. In this study, we investigated the roles of the mitochondrial, death receptor, and endoplasmic reticulum pathways in Aflatoxin B1 induced thymocytes apoptosis. Chickens were fed an aflatoxin B1 containing diet (0.6 mg/kg AFB1) for 3 weeks. Our results showed that (1) AFB1 diet induced the decrease of T-cell subsets, morphological changes, and excessive apoptosis of thymus. (2) The excessive apoptosis involved the mitochondrial pathway (up-regulation of Bax, Bak, cytC and down-regulation of Bcl-2 and Bcl-xL) and death receptor pathway (up-regulation of FasL, Fas and FADD). (3) Oxidative stress, an apoptosis inducer, was confirmed in the thymus. In conclusion, this is the first study to demonstrate that mitochondrial and death receptor pathways involved in AFB1 induced thymocytes apoptosis in broilers.

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The mitochondrial and death receptor pathways involved in the thymocytes apoptosis induced by aflatoxin B1.

In the present study, the ability of aflatoxin B1 (AFB1) to induce endogenous oxidative damages and the possible ameliorating effects of dietary melatonin (MEL) were investigated. Newly hatched broiler chicks (n = 240) were fed aflatoxin-contaminated diets (0.5 or 1 mg kg−1 diet) with or without MEL (40 mg kg−1 bw) supplementation in diet for 40 days. AFB1 resulted in a significant increase in lipid peroxidation (LPO) in the liver and erythrocytes accompanied with suppression of superoxide dismutase (SOD) and catalase (CAT) enzyme activities of erythrocytes. It also caused a significant reduction in levels of serum proteins and marked elevation in activities of serum transaminases. AFB1 treatment also decreased both humoral and cell-mediated immune responses in growing chicks. Simultaneous administration of MEL with AFB1 resulted in an obvious improvement in all the tested parameters. Long-term rather than short-term administration of MEL was more effective in rendering protection against AFB1-induced toxicity. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 153–160, 2011.

Protective effects of melatonin in reduction of oxidative damage and immunosuppression induced by aflatoxin B1-contaminated diets in young chicks

The aim of the present work was to determine whether the administration of melatonin or L-tryptophan (a precursor of melatonin) affects the immune responses and performance of broilers during induced exposure to aflatoxins in feed. The study was conducted from 0-6 weeks comprising six dietary treatments in triplicate with 10 chickens in each replicate. The diets were formulated to supply 23% crude protein (CP) and 2800 kcal ME/kg in starter ration and 20% CP and 2900 kcal ME/kg in finisher ration. The experimental diets were offered ad libitum with free access to water throughout the entire experiment. Inclusion of aflatoxin in the feed at 0.5 mg/kg feed caused a significant reduction in the growth performance of broilers. Supplementation of melatonin (20 mg/kg in feed and 20 mg/kg body weight through i.p. route) or its precursor (L-tryptophan at 250 mg/kg feed) in aflatoxin fed broilers resulted in numerically improved performance. Aflatoxin inclusion in the feed also caused a significant reduction in haemagglutination titer against sheep RBC and cell mediated immune responses to phytohemagglutinin (PHA-P) in broilers. Melatonin or L-tryptophan inclusion in toxin incorporated feed significantly improved both humoral and cell mediated immunity. No significant (P>0.05) differences were observed among various groups with respect to kidney and spleen weight but liver weight increased significantly (P≤0.05) and weight of bursa significantly decreased upon aflatoxin inclusion. Our study suggests that L-tryptophan was partially as effective as melatonin in alleviating aflatoxin induced growth retardation and immunosuppression in broiler chicken.

http://journals.iau.ir/article_514252_31f4511fcd3b0c3e0b20ca8e4e69ada2.pdf

M. Sirajudeen

Papers

Protective effects of melatonin in reduction of oxidative damage and immunosuppression induced by aflatoxin B1-contaminated diets in young chicks

Effect of Dietary Melatonin and L-Tryptophan on Growth Performance and Immune Responses ofBroiler Chicken under Experimental Aflatoxicosis