Review article
MOLECULAR INTERACTIONS BETWEEN MYCOTOXINS AND LIVER ENZYMES INVOLVED IN DRUG METABOLISM IN RODENTS AND FARM ANIMALS
Pierre Galtier
; Laboratoire de Pharmacologie-Toxicologie UR66 INRA, Toulouse, France
Guylaine Meissonnier
; Laboratoire de Pharmacologie-Toxicologie UR66 INRA, Toulouse, France
Joëlle Laffitte
; Laboratoire de Pharmacologie-Toxicologie UR66 INRA, Toulouse, France
Isabelle P. Oswald
; Laboratoire de Pharmacologie-Toxicologie UR66 INRA, Toulouse, France
Nicolas Loiseau
; Laboratoire de Pharmacologie-Toxicologie UR66 INRA, Toulouse, France
Abstract
Mycotoxins are well known for underging liver biotransformation in humans and animal species. Metabolites correspond to either oxydative derivatives such as hydroxymetabolites of aflatoxin B1 or ochratoxin A or hydrolytic derivatives in case of trichothecenes. In some cases, highly reactive epoxides represent the first step in the formation of carcinogenic intermediates like exo-epoxides of aflatoxins. Hepatic phase II enzymes including transferases and hydrolases are involved in the conjugation of such oxidative metabolites. In this respect, they are generally considered as detoxifying enzymes: glucuronidation of deacetylated trichothecenes or hydroxy-aflatoxins, or glutathione conjugation of epoxides. The major metabolism of zearalenone consists of reduction leading to estrogenic zearalenols which is characterized by large interspecies differences. Concerning fumonisin
B1, this toxin would be poorly absorbed from the gastrointestinal tract and metabolised into
hydrolytic products with lower toxic effect as apoptotic compounds. Interactions between mycotoxins and liver drug metabolizing are crucial in terms of detoxication or bioactivation of these toxins in the organism of the human or animal consumers. Most of these interactions are consequences of the metabolic processes occurring in the liver. They result generally from the activity of cytochromes P450 and transferases. In relation to their hepatotoxicity, several studies demonstrate the inhibitory
effects of mycotoxins on certain hepatic biotransformation enzymes, as recently demonstrated in pigs exposed to low doses of aflatoxin B1 or T-2 toxin. In other cases, specific cytochromes P450 or glutathione transferases are significantly increased in terms of both activity and protein expression, namely by aflatoxins, deoxynivalenol or fumonisins. Such results have been obtained in rodents and in farm animals like pigs, rabbits or poultry. The data strengthen the hypothesis that the normal metabolism of endobiotes or xenobiotics by the liver could be altered during chronic exposure to mycotoxins, particularly in farm animals or in humans exposed to aflatoxin B1, ochratoxin A, T-2 toxin,
deoxynivalenol or fumonisin B1.
Keywords
mycotoxins; liver enzimes; drug metabolism; rodents; farm animals
Hrčak ID:
28963
URI
Publication date:
9.10.2008.
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