Effects of methylmercury hydroxide on rat liver microsomal enzymes

Abstract

Subcutaneous administrations of methylmercury hydroxide (MMH) to male rats markedly reduced the content of microsomal cytochromes P-450 and b 5. The reduction was nearly 2-fold for P-450 in animals administered 2.5 mg/kg/day for 2 days. The decrease in P-450 levels corresponded both qualitatively and quantitatively to decreases in aminopyrine demethylase activity. The UDP glucuronyltransferase conjugating 1-naphthol and p-nitrophenol was unaffected by MMH treatment until the dose was increased to 10 mg/kg/day for 5 days, when a marked reduction in enzyme activity was observed. At all dosage levels used the animals exhibited no neurological symptoms, weight loss, or liver histopathology as determined by light microscopy. The decrease in cytochrome P-450 was maximal 24 h after a single treatment of MMH. The effect gradually diminished so that by 1 week after treatment there was no detectable effect on microsomal enzyme activity. Depression of aminopyrine demethylase on a per gram liver basis occurred primarily in the SER. The RER particles were markedly increased in number by MMH treatment but were not associated with increased mixed-function oxidase activity, whereas SER particles were decreased. The observed biochemical effects on the submicrosomal fractions were verified by electron microscopy. The large increase in RER was accompanied by a correspondingly large increase in polyribosomes and monoribosomes, while total RNA levels were unchanged by MMH pretreatment.