Study on the lipid composition of rat bile during choleresis induced by diethyl maleate.

Diethyl maleate (DEM) is known to produce a rapid depletion of hepatic glutathione (GSH) and to induce an immediate short-term choleresis in experimental animals. The aim of our investigation was to ascertain in rats the effect of DEM on biliary lipid composition during the increment in bile flow. Biochemical and morphological studies of liver tissue were conducted in parallel. In bile fistula rats, a doubling of bile flow occurred immediately after intraperitoneal injection of DEM (0.7 ml/kg body weight) returning to the basal level at 45 min. Choleresis diluted the total bile acid concentration, without modifying the secretion. The phospholipid concentration was not affected by DEM, resulting in increased output (p less than 0.02 vs. controls). Both cholesterol concentration and output were significantly decreased during DEM-induced choleresis. These changes were promptly reversible together with the return of bile flow to control values. Biochemical determinations failed to show a DEM-induced modification of enzymatic activities of the microsomal drug biotransformation pathway. Instead, morphological studies revealed alterations of the Golgi apparatus in hepatocytes with marked distension of the cisternae in coincidence with choleresis. The results demonstrate that the bile acid-independent choleresis induced by DEM is accompanied by an alternation in biliary lipid secretion possibly related to an interaction of the drug with the cellular or subcellular membranes of hepatocytes.