Parabolic response of hepatic microsomal hydroxylating system and lipids to graded doses of ascorbic acid in guinea pigs on low and high alpha-tocopherol intake.

The influence of marginal ascorbic acid (AA) deficiency and excessive AA consumption on hepatic microsomal cytochrome P-450, aniline hydroxylase and O-demethylase, serum and liver cholesterol, serum triglycerides and liver alpha-tocopherol was investigated in guinea pigs with low and high vitamin E intake. Male guinea pigs were fed 9 weeks a scorbutogenic diet low in vitamin E (6 mg alpha-tocopherol per kilogram diet), supplemented with four levels of AA: A, deficient, 1 mg AA per animal per day per os; B, control, 500 mg/kg diet; C, control, 5000 mg/kg diet; D, excess, 20,000 mg/kg diet. The response of the microsomal cytochrome P-450 and aniline hydroxylase, serum and liver cholesterol and serum triglycerides to increasing AA doses showed a parabolic pattern. Deficiency (A): high cholesterol in serum and liver, hypertriglyceridemia, low cytochrome P-450 and aniline hydroxylase in liver microsomes; control groups (B and C): decrease of serum and liver cholesterol and serum triglycerides, increase of cytochrome P-450 and aniline hydroxylase; excess (D): return of all parameters to values not significantly different from the AA-deficient group. When guinea pigs were fed the same diets with four levels of AA plus 10 mg alpha-tocopherol acetate per animal orally five times a week, the response of the microsomal hydroxylating system and serum triglycerides to the graded AA doses again proved to be parabolic.