Effects of chlorinated hydrocarbons on cellular volume regulation in slices of rat liver

Abstract

The effects of carbon tetrachloride and 1,2-dichloroethane (1,2DCE) on the recovery of slices of rat liver from cellular swelling in vitro were studied. Slices took up water during pre-incubation at 1°C, then cellular volume and ultrastructure were rapidly restored during subsequent incubation at 38°C. Ouabain (2 m m) inhibited water extrusion by less than 50%, while inducing formation of peri-canalicular vesicles, apparently derived from the Golgi apparatus. Neither CCl 4 nor 1,2DCE (up to 10 m m) affected the initial extrusion of water at 38°C in the absence of ouabain, but renewed swelling occurred after 60 min with either agent; this was associated with loss of membrane selectivity and some histological damage. By contrast, 1,2DCE inhibited water extrusion in the presence of ouabain after less intensive exposure, for example with 5 m m-1,2DCE for 60 min or 10 m m for 15–30 min. With ouabain present, 1,2DCE (10 m m) caused marked swelling of the endoplasmic reticulum, reduced the peri-canalicular vesicles seen with ouabain alone and reduced the formation of canalicular microvilli. Both CCl 4 and 1,2DCE inhibited the ATP-dependent accumulation of Cl − by isolated vesicles of the Golgi apparatus, The delayed swelling of hepatocytes at high concentrations of 1,2DCE and CCl 4 in the absence of ouabain is probably a non-specific consequence of membrane damage. By contrast, 1,2DCE specifically inhibits the ouabain-resistant extrusion of water, possibly by interfering with a postulated mechanism for the exocytotic expulsion of water.