Carbon Tetrachloride Changes the Activity of Cytochrome P450 System in the Liver of Male Rats: Role of Antioxidants
Posted: 10 Jul 2020
Date Written: December 14, 2001
The cytochrome P-450 enzymes are responsible for the oxidation of xenobiotic chemicals including drugs, pesticides, and carcinogens. These enzymes include cytochrome P450, cytochrome b5, arylhydrocarbon (benzo[a]pyrene) hydroxylase (AHH), NADPH-cytochrome C reductase and dimethylnitrosamine N-demethylase I (DMN-dI). Changes in the activities of the above mentioned enzymes were studied in the liver microsomes of rats treated with antioxidants (ascorbic acid (AA), dl-a-tocopherol (vitamin E, VE), garlic) as single- and repeated doses prior to the administration of a single dose of CCl4. Pretreatment of rats with single doses of AA, VE, or garlic prior to the administration of CCl4 was found to decrease the hepatic content of cytochrome P450, and the activities of DMN-dI and AHH. On the other hand, these treatments induced the hepatic content of cytochrome b5 and the activity of NADPH-cytochrome c reductase. Pretreatment of rats with repeated doses of AA, VE, or garlic for 12 consecutive days prior to the administration of CCl4 as single dose was potentially decreased the activities of cytochrome P450, DMN-dI and NADPH-cytochrome c reductase. Also, the activity of AHH decreased after treatments of rats with repeated doses of garlic prior to the administration of CCl4. It was noted that repeated doses of antioxidants are more effective than single dose in decreasing the activity of drug-metabolizing enzymes. It is concluded that repeated doses of antioxidants or garlic could reduce the toxic effects exerted by CCl4 upon the liver, and probably other organs, through inhibition of cytochrome P450 system that activates CCl4 into its active metabolite, trichloromethyl radical. Moreover, inhibition of cytochrome P450 system could also reduce the toxic and carcinogenic effects of chemical carcinogens such as benzo(a)pyrene and dimethylnitrosamine. The mechanisms of antioxidant protection were discussed in the text.
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