Dimethylnitrosamine, potent hepatotoxic and carcinogenic agent, is metabolized mainly in the liver, and its hepatotoxic action is influenced by the administration of phenobarbital which is inducer of hepatic drug-metabolizing enzyme.
In an effort to gather pathological data of the above, intraperitioneal injections of phen-obarbital(100mg/kg, for 3 successive days) were given daily to male albino rats and then 60 mg, 50 mg, 40 mg, and 30 mg of dimethylnitrosamine in physiologic saline solution intraperitoneally.
The mortality and hepatotoxicity in the experimental groups were as follows:
1. Mortality in 60 mg, 50 mg, 40 mg, and 30 mg injected rats indicated 80%, 50%, 40%, and 15%, whereas phenobarbital pretreated rats in corresponding group sustained 25%, 25%, 15%, and 5% of death rate, respectively.
2. The rats given 60 mg and 50 mg of DMN, cause acute massive hemorrhagic necrosis in the liver, and the necrotic changes were more extensive and intensive in the early experimental days, and progressed with lessened there after.
The phenobarbital pretreated groups were less intensive in their lesion and fastened their recovery than DMN-injected groups.
3. Necrotic changes in the 40 mg and 30 mg of DMN-injected groups developed mild to moderate degree in the first experimental day and got worse successive 1-2 days, whereas in phenobarbital pretreated group the lesions were more mild and shortened their course than those in DMN-injected groups.
4. Hepatic fibrosis in both DMN-injected and phenobarbital pretreated groups developed around the date when necrotic changes were subsiding, but in phenobarbital pretreated groups were less intensive and shorter course than each corresponding DMN-injected group.
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