HALOTHANE HEPATOTOXICITY AND HEPATIC FREE-RADICAL METABOLISM IN GUINEA-PIGS - THE EFFECTS OF VITAMIN-E

Purpose: The aim of this study was to investigate the relation between halothane hepatotoxicity and hepatic free radical metabolism and to e stablish a possible protective role of vitamin E against halothane hep atotoxicity. Methods: Twenty-eight guinea pigs were used in the experi ments. Halothane (1.5% v/v) in oxygen (100%) was given to the animals for 90 min over three days. Livers from animals were then taken and pr epared for the assays. In the enzymatic study, superoxide dismutase (S OD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities wer e measured. As a peroxidation index, the malondialdehyde (MDA) concent ration was determined. Also, electron spin resonance (ESR) analysis an d electron microscopy (EM) were performed. Results: Superoxide dismuta se (1168.3 +/- 78.2 U . mg(-1))and glutathione peroxidase (14.9 +/- 6. 2 mIU . mg(-1)) activities were decreased, but catalase activity (1260 .0 +/- 250.6 IU . mg(-1)) and malondialdehyde concentration (11.5 +/- 1.8 ppb) were increased in liver tissues exposed to halothane compared with control values (1382.2 +/- 98.8 U . mg(-1) for SOD, 27.8 +/- 5.2 mIU . mg(-1) for GSH-Px, 840.2 +/- 252.4 IU . mg(-1) for CAT and 10.0 +/- 1.0 ppb for MDA). Electron spin resonance analysis revealed a pea k of CF3CHCl. radical in the exposed tissue. Electron microscopy indic ated ultrastructural changes in the hepatic cells of both halothane gr oups with and without vitamin E treatment. Conclusion: Halothane cause s impairment in the hepatic antioxidant defense system and accelerates peroxidation reactions. As a result, some ultrastructural changes in hepatic tissues; occur due to halothane treatment. Although vitamin E prevents peroxidative damage, it does not ameliorate ultrastructural c hanges caused by halothane treatment. This shows that halothane toxici ty results nor only from impaired hepatic antioxidant defense system b ut also from other, unknown causes.