The effects of various drugs and toxic agents on bile flow rate and composition in the rat

Abstract

The effects of a number of hepatotoxic agents and other substances on bile flow rate have been investigated in the rat. Substances studied were: carbon tetrachloride, ethionine, dimethylnitrosamine, 2,4-dinitrophenol, sodium malonate, sodium succinate, sodium taurocholate, and sodium phenobarbital; the changes in bile flow rate were followed during the first few hours after dosing. Bilirubin excretion and rectal temperatures were also measured; in some cases total bile salt excretion and the pH of bile were determined. Carbon tetrachloride and dinitrophenol had no marked effect on bile flow under the conditions used; dimethylnitrosamine produced a transient choleresis 1 hr after dosing. Sodium taurocholate had a maximum choleretic effect approximately 20 min after an ip injection. Sodium succinate and sodium malonate produced rapid decreases in bile flow rate, but the succinate effect was relatively short in duration. Ethionine decreased bile flow rate rather slowly in female rats and even more slowly in male rats. Sodium phenobarbital had only a very small choleretic effect after correcting bile flow rate for the large increase in liver weight. The effects of the above-mentioned agents on bile flow are compared to previously published data concerning the action of the various agents on liver nicotinamide adenine dinucleotides. No correlation is apparent between the effects on bile flow and the changes in liver nucleotide content.