Influence of dietary carbohydrates (alpha-saccharides) on hepatic drug metabolism in male rats.

ABSTRACT

Young male rats (SD, CD strain) were fed semisynthetic isocaloric diets ad lib for different time periods (3,7,14, or 28 days); both carbohydrate (starch or sucrose) content and fat content were varied. High starch (HST) diet contained starch (73% of calories), corn oil (6%), and casein (21%); low starch (LST) diet contained 6, 73, and 21% of calories, respectively. In high sucrose (HS) or low sucrose (LS) diets, starch was replaced by sucrose. Rats fed LST and LS diets had decreased liver weight compared to those fed HST and HS diets, while liver microsomal protein content (mg/gm liver) was the same in all groups. Significant decreases in microsomal cytochrome P-450 from the basal level were observed in all diets over the period of experimental feeding. This decrease was more prominent with HST or HS diets compared to LST or LS dietary groups. HS diet feeding produced this decrease in cytochrome P-450 levels by 3 days; however, animals on HST diet required 7 days of feeding before they experienced a similar decrease in cytochrome P-450 levels. At 14 days, HST-fed animals had 52% lower liver microsomal cytochrome P-450 than did LST-fed animals. HS-fed animals had 36% lower cytochrome P-450 than LS-fed at 28 days. Similar results were observed for dietary effects on cytochrome b5. Aminopyrine demethylase activity decreased steadily on all diets. p-Nitrophenol glucuronidation was significantly increased in all dietary groups after 2 weeks of diet feeding. These results suggest that dietary carbohydrates and fat (particularly the relative quantities of carbohydrate and fat) may significantly influence the hepatic drug-metabolizing enzymes. It is speculated that these changes may occur due to alteration in the phospholipid composition of endoplasmic reticulum or by limiting the supply of cofactor(s) necessary for optimal mixed function oxidation and conjugation.