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Effect of large doses of ascorbic acid on the hepatic and extra-hepatic drug-metabolizing enzymes in guinea pig.

Water solubility and non-toxic properties of ascorbic acid are taken as criteria for beneficial effects of large doses of the vitamin. In the present study, male guinea pigs, dosed daily with 15, 30 or 50 mg/100g body weight for 10 weeks, demonstrated no differences in effect on liver and lung weights, body growth and microsomal protein contents of liver and lung when compared with controls. When guinea pigs were fed excessive ascorbic acid, there was a small non-significant increase (p less than 0.05) in hepatic and pulmonary cytochrome P-450, and significant increase (p less than 0.05) in hepatic cytochrome b5 which was accompanied with a significant increase in arylhydrocarbon hydroxylase activity in the two organs. Activity of NADPH-dependent cytochrome c-reductase was decreased in liver and remained unaffected in lung and colon. Drug detoxifying enzymes responded in different ways to increased intake of ascorbic acid. Activity of UDP-glucuronyltransferase remained unchanged on feeding excessive ascorbic acid, whereas glutathione S-transferase was decreased significantly in liver and was unaltered in lung and colon. Reduced glutathione was decreased only in the lung. The observed changes in drug activating and detoxifying enzymes appear to be important from drug pharmacokinetics and carcinogenesis point of view.