EFFECTS OF CARBON-TETRACHLORIDE AND CHLOROFORM ON BILE-ACID TRANSPORTIN ISOLATED RAT HEPATOCYTES - RELATIONSHIP TO ELEVATED SERUM BILE-ACIDS

The hepatotoxic effects of chlorinated hydrocarbon solvents have been well recognized for many years. More recently serum bile acids (SBA) h ave been considered as a sensitive indicator for the determination of liver dysfunction. However, changes in SBA could result from interfere nce with hepatic transport processes. In this study, the effects of ca rbon tetrachloride (CCl4) and chloroform (CHCl3) on uptake and efflux of bile acids were examined in isolated rat liver cells to determine w hether this may play a role in elevated SBA after CCl4 or CHCl3 treatm ent. Cholic acid (CA) and taurocholic acid (TC) were selected as repre sentative bile acids known to enter hepatocytes by active transport. A t none of the doses of CCl4 and CHCl3 investigated was there a signifi cant change in cytoplasmic enzymes or intracellular K+ release. CCl4 a nd CHCl3 were both found to cause a dose-related inhibition of uptake of CA and TC. Furthermore, CCl4 and CHCl3 were shown to increase the M ichaelis constant (K(m)) but leave maximum velocity (V(max)) unchanged thus indicating competitive inhibition. The lowest doses of CCl4 and CHCl3 at which inhibition of initial uptake rate (V0) occurred for CA or TC were found to be 0.5 mul/flask (0.07 mm) or 1.0 mul/ flask (0.17 mm) in cell suspensions, respectively. The inhibition of uptake could be reversed 30 min after cessation of exposure to CCl4. No chemical-i nduced interference of efflux for CA or TC was found in preloaded cell s. These findings indicate that interference in bile acid uptake may b e involved, at least in part, in the increases in SBA in dosed animals , or workers exposed to CCl4, CHCl3 and perhaps other chlorinated solv ents.