Halothane-induced lipid peroxidation and glucose-6-phosphatase inactivation in microsomes under hypoxic conditions.
Halothane-induced lipid peroxidation was studied in microsomes from phenobarbital-pretreated male rats at defined steady state oxygen partial pressures (PO2). At PO2 less than 10 mmHg on addition of halothane to NADPH-reduced microsomes, significant increases in malondialdehyde (MDA) formation, oxygen uptake, and conjugated dienes were measured. At the maximum, near a PO2 of 1 mmHg, halothane induced the formation of about 0.75 nmol MDA X mg microsomal protein-1 X min-1; it also stimulated microsomal oxygen uptake twofold to threefold, and caused an almost threefold increase in conjugated diene absorption. Moreover, at this PO2 microsomal glucose-6-phosphatase lost about 70% of its activity. At PO2 greater than 10 mmHg, no significant effects of halothane on MDA formation, oxygen uptake, conjugated diene absorption, and glucose-6-phosphatase activity were observed; likewise under anaerobic conditions there was only a slight increase in conjugated dienes. The findings demonstrate that halothane induces microsomal lipid peroxidation at low PO2 and in the presence of particular cytochrome P-450 isoenzymes, and that the halothane-induced lipid peroxidation leads to severe microsomal lesions, as indicated by the loss of glucose-6-phosphatase activity.
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D000818:Animals; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D008315:Malondialdehyde; D005952:Glucose-6-Phosphatase; D010100:Oxygen; D006221:Halothane