Isoniazid, a widely used antituberculous drug, were oxidized by cytochrome p450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents, and this process were potentiated by pretreatment with phenobarbital.
To evaluate the histopathological changes for the influences of isoniazid treatment and phenobarbital pretreatment, each intraperitoneal injections of physiologic saline solution, 100mg of phenobarbital, or 200mg of phenobarbital were given to male albino rats, and then each 500mg/kg of isoniazid in physiologic saline solution also were given intraperitoneally.
The results obtained were as follows:
1. The mortality in isoniazid only treated rats was 0%, in phenobarbital 100mg pretretaed rats was 0%, and in phenobarbital 200mg pretreated rats was 25%.
2. The hepatic cellular necrosis in isoniazid only treated rats was mild on the 2nd day of experiment, whereas phenobarbital 100mg pretreated rats was mild on the 3rd day and moderately progressed on the 6th day. The phenobarbital 200mg pretreated rats revealed moderate necrotic change after the 2nd day of experiment.
3. On reticular staining, derangement of reticular fibers in isoniazid only treated rats was also mild on the 2nd day of experiment.
The phenobarbital 100mg pretreated rats were noted mildly on the 3rd day of experiment, but intensively changed after the 5th day, compared with marked irregularity after the 2nd day in 200mg pretreated rats.
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