Isoniazid를 투여받은 흰쥐에서 cimetidine의 전투여가 halothane 마취시 간에 미치는 영향에 대한 연구

초록

The H₂-receptor antagonist, cimetidine, through binding of its imidazole group to cytochrome p-450, has been known to inhibit drug metabolism. The intermediate products of oxidative metabolism appear to be involved in the etiology of halothane-induced hepatotoxicity following isoniazid treatment. The study was undertaken to determine the effect of cimetidine on the halothane hepatotoxicity in isoniazid pretreated rats. Seventy two Sprague-Dawley rats were divided into three groups. Saline was injected intraperitoneally daily for 7 days in group Ⅰ(N=24). Isoniazid(50 mg/kg) was injected intraperitoneally daily for 7 days in group Ⅱ(N=24) and group Ⅲ(N=24). Cimetidine(180 mg/kg) was injected one hour before halothane anesthesia in group Ⅲ. All of the three groups were exposed to halothane-N₂O-O₂(1%-3L/min-3L/min) 24 hours after last treatment with saline or isoniazid. Blood sampling was done before any treatment through tail vein. Intracardiac puncture for blood sampling was done after intraperitoneal injection of pentobarbital(50 mg/kg) and hepatectomy was done to get the tissue sample for light microscopic examination 24 hour after halothane anesthesia in one-half of the rats from each group ; the remaining were examined 96 hours after halothane anesthesia. Biochemical studies included liver and renal function variables(protein, albumin, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine). The results are summarized as follows : 1. The histologic evidence of hepatic damage was shown in gruop Ⅱ & Ⅲ 24 hours after halothane anesthesia, but 96 hours after halothane anesthesia, only group Ⅱ showed the histologic evidence of hepatic damage. 2. The laboratory findings 24 hours after halothane anesthesia showed decreased values in all three groups, but there was no significant differences in all three groups. The value of ALP was decreased in group Ⅰ & Ⅱ and that of AST in group Ⅱ & Ⅲ. 3. Most of the laboratory findings 96 hours after halothane anesthesia revealed decreased values in all three groups, but there was no significant differences in all three groups. BUN & ALT in group Ⅰ, creatinine in group Ⅱ and ALP in group Ⅱ & Ⅲ showed decreased values. Above results suggest that cimetidine can not protect halothane induced hepatotoxicity with isoniazid pretreatment but may have some influences on the hepatic regenerativity.

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