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-31L/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 a and renal function variables protein. albumin, total bilirubin, direct bilirubin, alanine aminotransferase. aspartate aminotransferase. alkaline phosphatase. blood urea
nitrogen,
creatinine).
@ES The results are summarized as follows:
@EN 1. The histologic evidence of damage was shown in group 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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