In vitro interference with hepatocellular transport of taurocholate by 1,1,2-trichloro-1,2,2-trifluoroethane

Abstract

In recent years workers in our laboratory have shown that several industrial chlorinated aliphatic hydrocarbon solvents interfere with the transport of bile acids by hepatocytes and this interference may account for the raised concentration of serum bile acids that has been observed after occupational exposure to solvents. There has been concern about the effects on workers of a selective solvent used in degreasing electrical equipment, 1,1,2-trichloro-1,2,2-trifluoroethane (FC 113). However, this compound has not been investigated for effects on bile acid transport. Therefore we undertook the present study to examine the direct in vitro effects of FC 113 on uptake and efflux of bile acids by isolated rat hepatocytes. FC 113, at non-cytotoxic doses after a 20-min equilibration time, showed significant ( P < 0.05) inhibitory effects on the initial rate of uptake of taurocholate (TC), whereas accumulation of TC over an extended incubation time was not affected. Kinetic analysis revealed a non-competitive inhibition of TC uptake as evidenced by a decline in V max and an unaltered K m. The initial rate of efflux of TC and the continuous efflux of this model substrate from preloaded cells incubated with different doses of solvent were not significantly different from those of controls. However, the highest dose of solvent inhibited the process of efflux at the early time points. The data suggest that FC 113 interferes with bile acid transport in a reversible manner similar to that of the chlorinated aliphatic hydrocarbons. It would be expected, therefore, that this solvent would cause an increase in serum bile acids in exposed workers.