Cholestasis and increased biliary excretion of inulin in rats given 1,1-dichloroethylene

Bile flow and biliary excretion of the inert solute [3H]inulin were monitored in unanesthetized, freely moving male rats for 4 h after oral administration of 1,1-dichloroethylene (1,1-DCE) at a dose of 200 mg/kg. Comparisons were made between 4 groups: fed-controls, fed-1,1-DCE treated, fasted-controls, and fasted-1,1-DCE treated. Biliary inulin excretion was assessed at 30-min intervals as total excretion and as bile/plasma ratio. 1,1-DCE treatment was consistently associated with at least a 2-fold increase in both parameters of inulin excretion within 2 h after toxin administration. In contrast, 1,1-DCE treatment was not associated with changes in plasma inulin values at any time or in liver/plasma inulin ratios at 4 h. Bile flow decreased in all groups: gradually by 30% in the fed and fasted controls, by 40% in the fed-1,1-DCE treated group, and markedly by 65% in the fasted-1,1-DCE treated group. Liver damage at 4 h as reflected by elevated plasma activities of liver-derived enzymes was found only in fasted-1,1-DCE treated rats. Thus the cholestatic effect of 1,1-DCE appears related to the development of liver damage whereas other aspects of the hepatic response to 1,1-DCE may enhanced biliary excretion of inulin.