title: Effect of dietary vitamin E on methyl ethyl ketone peroxide damage to microsomal cytochrome P-450 peroxidase.
abstract: The effect of dietary vitamin E on in vivo and in vitro damage by methyl ethyl ketone peroxide (MEKP) to cytochrome P-450 and its associated enzymatic activity was studied. In vivo, MEKP damaged microsomal cytochrome P-450 and cytochrome P-450-mediated peroxidases in vitamin E-deficient rat liver. Dietary vitamin E treatment of rats protected the microsomal enzymes from peroxide damage. In vitro, the extent of MEKP inhibition was different for tetramethylphenylenediamine (TMPD)-peroxidase, NADH-peroxidase, and aminopyrine demethylase. In vitro addition of MEKP induced production of more thiobarbituric acid reacting substances (TBARS) in liver microsomes from vitamin E-deficient rats than from vitamin E-supplemented rats. When NADH and/or NADPH were supplied as reductants of MEKP, the inhibition of aminopyrine demethylase activity and the generation of TBARS by added MEKP were markedly reduced. In vivo, adequate levels of vitamin E and of NADH and NADPH are probably necessary to provide important protection to the endoplasmic reticulum during metabolism of toxic organic peroxides, such as MEKP.
mesh_terms: D000818:Animals; D002074:Butanones / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000502:physiology; D010544:Peroxidases / Q000378:metabolism*; D010545:Peroxides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D002074:Butanones; D006420:Hemeproteins; D008054:Lipid Peroxides; D010545:Peroxides; C011007:methyl ethyl ketone peroxide; D014810:Vitamin E; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D010634:Phenobarbital