Low protein diets potentiate lithocholic acid-induced cholestasis in rats

Earlier studies showed that low protein diets (LPD) reduce bile flow and bile acid secretion. We therefore examined the effect of LPD on lithocholic acid (LCA)-induced intrahepatic cholestasis. Female Sprague-Dawley rats were fed LPD (8% casein) soon after weaning for 4 or 12 wk, and then were injected intravenously with a single dose of LCA (4 mumol/100 g body wt). Bile was collected for 30-min periods, and bile flow as well as biliary lipid secretory rates were measured. Bile acid metabolism was also studied and the results were compared with those obtained in rats fed an adequate protein diet (26% casein). The LPD produced significantly lower bile flow and bile acid secretion, which were attributed to a reduced bile acid pool and a reduction in synthesis. They also enhanced the LCA-induced decline in bile flow, and rate of biliary output of total bile acids, phospholipids and cholesterol. The LPD were also associated with impaired LCA secretion in bile and increased retention in plasma and liver. Studies of LCA metabolism in rats fed a LPD indicated lower hepatic LCA hydroxylation, a greater percent contribution of glyco conjugates and lower levels of tauro conjugates. The present findings suggest that the reduced bile acid pool size, diminished LCA excretion and biotransformation to less toxic bile acids may explain the greater cholestasis in LPD-fed rats.