Relation between renal and hepatic excretion of drugs: VII. Hepatic and renal excretion of phenol red in thioacetamide-induced a cute and chronic liver damage

Abstract

Acute and chronic liver damage was induced in rats by thioacetamide (TAA). Centrilobular liver cell damage associated with an accumulation of lipid droplets was produced by a single high dose (10 mg TAA/100 g b.m.). Liver fibrosis, micronodular and macronodular liver cirrhosis were induced by chronic TAA treatment (300 ml/l drinking water for 1.5, 3 or 6 months). Acute administration of TAA caused a significant decrease of hepatic phenol red excretion but no compensatory increase of its urinary excretion. In contrast, 24 h after bile duct ligation renal excretion of the dye increased by about 50%. After chronic exposure to TAA for three months hepatic phenol red excretion remained reduced and renal excretion raised significantly. This compensatory increase of urinary excreted phenol red amounts did not occur after 6 months of TAA treatment, probably as a result of additional nephrotoxicity of TAA. Two weeks after cessation of TAA exposure for 3 months, hepatic and renal phenol red excretion returned to normal. Bile flow per animal increased significantly after 3 months of TAA exposure. Apparently this is due to a reduced intrahepatic reabsorption of canalicular bile in TAA-damaged liver.