An organic peroxide, methyl ethyl ketone peroxide, damage to cytochrome P-450 peroxidase and microsomal enzymes activity

Abstract

In vivo, an organic peroxide, methyl ethyl ketone peroxide (MEKP) damaged microsomal cytochrome P-450 and cytochrome P-450 peroxidase in vitamin E deficient rat livers. Dietary vitamin E protected the microsomal enzymes from MEKP damage. Phenobarbital induced liver cytochrome P-450 peroxidase and glutation S-transferase and decreased MEKP damage on microsomal enzymes. MEKP induced production of more lipid peroxides (TBARS) in liver microsomes from vitamin E deficient rats than from vitamin E supplemented rats. Cytochrome P-450 and aminopyrine demethylase from vitamin E deficient rat microsomes were damaged to a greater extent by MEKP than were those from vitamin E supplemented rat microsomes. MEKP markedly inhibited liver microsomal TMPD- and NADH-peroxidase. In vivo, adequate levels of vitamin E, NADH, and NADPH are probably necessary to provide important protection to the endoplasmic reticulum from damage by organic peroxides.