The effects of T-2 toxin exposure on liver drug metabolizing enzymes in rabbit.
High doses of T-2 toxin are known to decrease protein synthesis and mono-oxygenase activities in rat liver. The purpose of this study was to investigate whether exposure at a low dose could alter the normal metabolism of the xenobiotic by the liver. Three doses of T-2 toxin, dissolved in olive oil, were orally and daily administered to New Zealand white rabbits for five days. At 0.5 mg/kg, three of the five animals died, whereas only a weak decrease in body weight gain and moderate signs of toxicity occurred in rabbits receiving 0.25 mg/kg/day, and the body weight increased without signs of toxicity at 0.1 mg/kg/day. At 0.25 mg/kg/day, total liver microsomal P450 content, and the activities of aminopyrine and benzphetamine N-demethylases, pentoxyresorufin O-depentylase, glutathione S-transferases accepting 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates, were decreased. By contrast, ethylmorphine and erythromycin N-demethylases, ethoxyresorufin and methoxyresorufin O-dealkylases, aniline hydroxylase, and UDP-glucuronyltransferase accepting p-nitrophenol as substrate, were unaffected. The expression of P450 1A1, 1A2, 2A1, and 2B4, but not P450 2C3 and 3A6, were also decreased, whereas microsomal conjugated dienes, fluorescent substances, and malondialdehyde contents were increased. At 0.1 mg/kg/day, neither significant effects on drug metabolizing enzymes nor microsomal oxidative damages were obtained. Taken together, these results suggest that a short exposure time to the mycotoxin would not be associated with significant changes in the normal metabolism of xenobiotics by the liver.
Laboratoire de Pharmacie-Toxicologie, E.N.V.T., 23 Chemin des Capelles, 31076 Toulouse, France.
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Guerre
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Eeckhoutte
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Burgat
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Galtier
D000818:Animals; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D011817:Rabbits; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
D014255:Trichothecenes; D003577:Cytochrome P-450 Enzyme System