Prevention of carbon tetrachloride-induced lipid peroxidation in liver microsomes from dehydroepiandrosterone-pretreated rats.
Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered to rats (100 mg/kg b.wt) by a single intraperitoneal injection, increases to twice its normal level in the liver microsomes. Microsomes so enriched become resistant to lipid peroxidation induced by incubation with carbon tetrachloride in the presence of a NADPH-regenerating system: also the lipid peroxidation-dependent inactivation of glucose-6-phosphatase and gamma-glutamyl transpetidase due to the haloalkane are prevented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P450IIE1, responsible for the CCl4-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the protein covalent binding of the trichloromethyl radical (CCl3 degrees), is similar to that of not supplemented microsomes treated with CCl4. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant properties rather than inhibiting the metabolism of the toxin.
Department of Experimental Medicine and Oncology, General Pathology Section, Torino, Italy.
M
M
Aragno
E
E
Tamagno
G
G
Poli
G
G
Boccuzzi
E
E
Brignardello
O
O
Danni
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology; D019392:Cytochrome P-450 CYP2E1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism
D015415:Biomarkers; D065607:Cytochrome P-450 Enzyme Inhibitors; D003687:Dehydroepiandrosterone; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D015660:7-Alkoxycoumarin O-Dealkylase; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D005723:gamma-Glutamyltransferase; D005952:Glucose-6-Phosphatase