Metabolism of AflatoxinB1 – a natural contaminant in Poultry

AFB1 is the most potent of the naturally occurring mycotoxins. It is a secondary metabolite of the Aspergillus flavus and Aspergillus parasiticus fungi, and it is found in grains and other foods and feeds as a natural contaminant. It is an extremely toxic and a powerful carcinogen and, therefore, represents a serious risk to health in Poultry. In addition, AFB1 causes various health effects in chickens in a dose-response pattern. AFB1 is metabolized by hepatic microsomal cytochrome P450s (P450) to the reactive, electrophilic exo-AFB1-8,9-epoxide (AFBO) which binds to DNA and other critical cellular macromolecules. The AFBO is highly unstable, and reacts with the DNA to form N7 guanine adducts by intercalation of AFBO between base pairs.
Role of cytochrome P450s
Cytochrome P450s are mixed function oxidases that catalyze the biotransformation of a wide variety of xenobiotics. They are a superfamily of hemoproteins that aid in the oxidation of various substrates such as steroids, eicosanoids, pharmaceuticals, pesticides, pollutants, and carcinogens. Cytochrome P450s plays an important role in the formation of carcinogenic and mutagenic electrophilic intermediates from naturally-occurring dietary compounds, AFB1 is not toxic, but requires metabolic conversion to the reactive and electrophilic exo-AFBO by P450s to exert its toxicity. This electrophilic metabolite reacts with cellular nucleophiles and can induce mutations by alkylating DNA, principally at the N7 position of guanine forming the 8,9-dihydro- 8-(N7-guanyl)-9-hydroxy-AFB1. In addition, AFBO can bind to proteins and other critical cellular nucleophiles.
Poultry liver P450s are especially efficient toward AFB1 bioactivation. When comparing livers obtained from 9, 45, and 61 day-old turkeys, microsomes from younger were more active toward AFB1 bioactivation than that from older birds and that’s why young ones are more prone to the toxicity.
Hepatic mixed-function oxydase system biotransforms AFB1 and generates an aflatoxin metabolite or reactive epoxide. This intermediate molecule is inactivated by conjugation with reduced glutathione (γ-glutamil-cysteinyl-glycine, GSH). This reaction is catalyzed by glutathione-S-transferase (GST) to form a molecule that is eliminated as mercapturic acid-AFB1 (8,9-dihidro-8-9-(S-cysteinyl-(N-acetyl))-9-hydroxy aflatoxin B1) or N-acetylcysteine (NAC) bound to AFB1. When birds eat AFB1, it is absorbed by the intestine and distributed by the bloodstream throughout the body; approximately 90% AFB1 is removed through bile and renal secretion. In laying hens and broiler chickens, aflatoxin clearance times are 24 h for muscle and 8 d for eggs. For these reasons, intensive research has been pursued to develop cost-effective and safe procedures and agents that reduce the deleterious effects of AFB1.
Aflatoxin B1 is the most common aflatoxin affecting poultry industry worldwide, toxin binders have been used to bind the toxin in feed but once the toxin is inside the gut or in the circulation these toxin binders donot work, recent advances in research on aflatoxins focuses on the methods to eliminate the toxin by either binding with it or not letting the procarcinogen(AFB1) moiety to change in to active moiety that is exo-AFB1-8,9-epoxide (AFBO). And there are such compounds available which when given in the appropriate dose can prevent the harmful effects of aflatoxins already present in the circulation or in feed, of these compounds, methione, cystine, NAC, Selenium, Vitamin E have been already used with great efficacy while some more effective compounds can be used.
by Dr. Meesam Raza, Poultry Consultant