Effect of prototypic polychlorinated biphenyls on hepatic and renal vitamin contents and on drug-metabolizing enzymes in rats fed diets containing low or high levels of retinyl palmitate

Abstract

Two groups of weanling male Sprague-Dawley rats fed a diet supplemented with either 0.6 or 6 retinol equivalents/g diet were each separated into three further groups receiving 300 μmol 2,2′,4,4′,5,5′-hexachlorobiphenyl/kg body weight, 300 μmol 3,3′,4,4′-tetrachlorobiphenyl kg/body weight or vehicle only (corn oil). Only the coplanar (3,4) 2Cl congener caused a slight reduction in food intake, thymic atrophy and led to a significant decrease in the liver vitamin A storage. The vitamin A lost by the liver was approximately the same in both dietary groups; however an increased renal accumulation of vitamin A was observed in the high vitamin A group. Serum retinol was reduced by (3,4) 2Cl treatment but remained unchanged by (2,4,5) 2Cl exposure. Total amounts of ascorbic acid and its oxidation products were increased in the liver and in the kidney by both xenobiotics while niacin and thiamine concentrations were lowered by (3,4) 2Cl only. Microsomes from vitamin A-deficient rats exhibited a marked decrease in the anisotropy parameter. After (2,4,5) 2Cl exposure, an increase in membrane fluidity was observed linked to a decrease in cholesterol/phospholipid (C/P) ratio. Treatment with (3,4) 2Cl caused a significant decrease in the index of fluorescence polarization only in the low vitamin A group even if the C/P ratio was enhanced in both dietary groups. This study shows that the polychlorinated biphenyl with the 3-methylcholanthrene-type pattern of induction of cytochrome P-450 has more profound effects on B group vitamins and particularly vitamin A homoeostasis than does the phenobarbital-type inducer. Moreover, this situation, which has been found to be similar to that in vitamin A deficiency, is not ameliorated by a high dietary vitamin A intake.