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 ASA 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 excised and fixed. Uncoupling of oxidative phosphorylation was observed in mitochondria isolated from ASA-treated rats. Although no histological changes were evident, lamellar structures in bile canaliculi were ultrastructurally observed in all rats treated with ASA.

Conclusions: This laminar structure, which is negative for bilirubin staining, seems to be one of the most sensitive indicators of ASA-induced liver damage.