Inhibition by trichloroethylene and 1,1,2-trichloro-1,2,2-trifluoroethane of taurocholate uptake into basolateral rat liver plasma membrane vesicles.
It has previously been shown that trichloroethylene (TRI) and 1,1,2-trichloro-1,2,2-tri-fluoroethane (FC 113) interfere with the transport of bile acids by isolated human and rat hepatocytes in a dose-dependent and reversible manner. This finding may explain the rise in serum bile acids (SBA) following exposure to these chemicals. However, the effect of these compounds on the transport of bile acids across the cellular membrane in the absence of confounding variables, such as interference by intracellular metabolism, binding to cytosolic proteins and intracellular conjugation, has not been investigated. Accordingly, in vitro effects of TRI and FC 113 on uptake of [(3)H]taurocholate (TC) into purified basolateral (blLPM) and canalicular (cLPM) rat liver plasma membrane vesicles were examined by a rapid filtration technique. Both TRI and FC 113 caused a dose-dependent inhibition of TC uptake into blLPM vesicles at an approximate concentration of 3 mm and 72 mum, respectively. Initial rates of TC uptake in the presence of TRI and FC 113 were significantly inhibited by 69 and 61%, respectively (P < 0.05). In contrast, these chemicals had no effect on TC uptake into cLPM vesicles. This confirms studies in intact cells where these solvents were found to inhibit the uptake of bile acids by hepatocytes rather than interfere with the process of efflux. In conclusion, and consistent with the previous findings, the data suggest that the mechanism of TRI and FC 113-induced elevation of SBA may, in part, be due to selective inhibition of bile acid transport by the parent compounds at the basolateral domain of the hepatocyte plasma membrane.
Neghab
M
M
Toxicology Unit, National Institute of Occupational Health and Safety (Worksafe Australia), The University of Sydney, GPO Box 58, Sydney NSW 2001, Australia.
Hamdan
H
H
Edwards
R J
RJ
Stacey
N H
NH