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-ox ygenase activities in rat liver. The purpose of this study was to investiga te 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 da ys. At 0.5 mg/kg, three of the five animals died, whereas only a weak decre ase 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 to xicity at 0.1 mg/kg/day. At 0.25 mg/kg/day, total liver microsomal P450 con tent, and the activities of aminopyrine and benzphetamine N-demethylases, p entoxyresorufin O-depentylase, glutathione S-transferases accepting 1-chlor o-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates, were de creased. By contrast, ethylmorphine and erythromycin N-demethylases, ethoxy resorufin 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 subs tances, and malondialdehyde contents were increased. At 0.1 mg/kg/day, neit her significant effects on drug metabolizing enzymes nor microsomal oxidati ve damages were obtained. Taken together, these results suggest that a shor t exposure time to the mycotoxin would not be associated with significant c hanges in the normal metabolism of xenobiotics by the liver.