Primary changes in liver damage by aspirin in rats

Background: It has been known that acetylsalicylic acid (ASA) causes liver cell damage, however, its mechanisms remain obscure. Methods and results: To clarify the earliest change in the course of liver cell damage induced by oral administration of ASA, rats that had received A SA at 50 mg/kg and 150 mg/kg bodyweight orally for 7 days were investigated . Mitochondria were isolated for measurements of mitochondrial respiration, and for electron microscopic observations, small pieces of liver were exci sed and fixed. Uncoupling of oxidative phosphorylation was observed in mito chondria isolated from ASA-treated rats. Although no histological changes w ere evident, lamellar structures in bile canaliculi were ultrastructurally observed in all rats treated with ASA. Conclusions: This laminar structure, which is negative for bilirubin staini ng, seems to be one of the most sensitive indicators of ASA-induced liver d amage.