Vitamin A levels in regenerating rat liver. Effects on microsomal drug metabolism

Abstract

After being maintained on a vitamin A-deficient or complete diet for a period of five weeks, male Sprague-Dawley rats were subjected to a two-thirds partial hepatectomy (PH) or sham operation. The vitamin A content of the liver of vitamin A-deficient, PH rats was below the limit of detection (less than 1 microgram/g liver). Rats fed the control diet and subjected to PH had hepatic levels of vitamin A that were 37% and 49% lower 48 and 72 hours after surgery, respectively, when compared with sham-operated controls. Hepatic microsomal cytochrome P-450 levels were significantly reduced in PH rats fed the complete diet 48 hours after PH and in PH rats fed either the deficient or complete diet 72 hours after. Vitamin A deficiency alone significantly reduced cytochrome P-450 levels. A combination of vitamin A deficiency and PH had the most dramatic effect on cytochrome P-450 and aminopyrine N-demethylase, which reduced the activity to approximately 50% of the activities found in the sham-operated control group. PH resulted in the greatest reduction in the rate of disappearance of benzo[a]pyrene in the presence of liver microsomes prepared from vitamin A-deficient rats.