Induction of drug metabolizing enzymes in the liver of diabetic mice.
The effects of two classical inducers, phenobarbital and 3-methylcholanthrene, have been tested on some liver microsomal drug-metabolizing enzymes (monooxygenases and phase II enzymes) and on benzo(a)pyrene metabolism in genetically (ob/ob) and chemically (streptozotocin) diabetic mice. 1) In ob/ob mice, the basal activities and the inducibility of phase I and phase II enzymes, as well as the electrophoretic pattern of microsomal proteins, were not notably different from those of similarly treated lean mice. 2) A possibly common form of cytochrome P 450 present both in microsomes from steptozotocin-diabetic non-induced mice and in those from phenobarbital-treated non-diabetic mice could explain the increased "phenobarbital-like" enzyme activities in chemically diabetic animals. 3) The increase of monooxygenase activities produced by streptozotocin treatment is partially depressed by 3-methylcholanthrene, probably as a result of the dilution of "phenobarbital-like" cytochrome P 450 forms by 3-methylcholanthrene-induced cytochrome P 448. 4) The increased formation of the most carcinogenic metabolites of benzo(a)pyrene, and the slight decrease of phase II conjugation enzyme activities, may add their deleterious effects in 3-methylcholanthrene-induced streptozotocin-diabetic animals.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D010634:Phenobarbital