Dimethylnitrosamine, potent hepatotoxic and carcinogenic agent, is metabolized mainly in the liver, and its hepatotoxic action is influenced by the administration of phenoba￢rbital which is thought as inducer of hepatic drug-metabolizing enzyme.
In order to study the effects of phenobarbital pretreated dosage on the hepatotoxic changes of dimethylnitrosamine, phenobarbital were administered with 100mg every consecutive day to the male albino rats intraperitoneally, and then 60mg, 50mg, 40mg, and 30mg/kg of dimethylnitrosamine in physiologic saline solution were given by intraperitoneal injection.
The mortality and histopathologic changes between control (dimethylnitrosamine only) and experimental groups were as follows:
1. Mortality in 60mg, 50mg, 40mg and 30mg injected rats indicated 80%, 50%, 40% and 15%, whereas phenobarbital 3 successive days pretreated rats in corresponding group sustained 25%, 20%, 15%, and 5% of death rate, respectively, 6 successive days Pretreated rats 30%, 20%, 20% and 10%, 9 successive days´ pretreated rats 75 0, 70% and 17%.
2. The rats given 60mg, and 50mg of DMN, cause acute massive hemorrhage in the
liver, and then the necrotic changes were more extensive and intensive in the early expe￢rimental days, and progressed with lessened thereafter. The phenobarbital 300mg pretr￢eated groups were less intensive in their lesions and fastened their recovery than DMN￢-injected groups.
The hemorrhagic necrotic changes in phenobarbital 600mg and 900mg phenobarbital groups, were less intensive on the first day of experiment, compared with 300mg pretr￢eated groups, but after that more intensive and prolonged.
3. Necrotic changes in the 40mg and 30mg of DMN injected groups developed mild to
moderate degree in the first experimental day, and became worse in successive 1-2 days, whereas in phenobarbital 300mg pretreated groups the lesions were more mild and short￢ened their course than those in DMN injected groups, but in phenobarbital 600mg and ´900mg pretreated groups, necrotic changes were mild on the first day of experiment, but .after that became more intensive and prolonged.
4. Hepatic fibrosis in both DMN-injected and phenobarbital pretreated groups developed around the date when necrotic changes were subsided, but in phenobarbital pretreated groups were less intensive and shorter course than each corresponding DMN-injected group.
There are no specific relationships between necrotic or fibrotic change and phenobar￢bital pretreated dosage.
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