Structural and functional impairment of mitochondria from rat livers chronically injured by thioacetamide.

The effect of prolonged application of thioacetamide (TAA) on structural and functional properties of isolated liver mitochondria from rats was studied. Mitochondria prepared either from micronodularly cirrhotic livers (TAA application for 3 months) or from macronodularly cirrhotic ones (TAA application for 6 months) exhibited loss of respiratory control due to increased state 4 respiration and decreased state 3 respiration. The mitochondrial content of cytochromes aa3 and b was lowered only after 6 months exposure to TAA. The Mg2+ content of mitochondria from macronodularly cirrhotic livers was reduced to 50%. Mitochondria isolated from rats chronically treated with TAA exhibited lowered Ca2+ uptake rates and a decreased Ca2+ retention time. The analysis of mitochondrial phospholipid fatty acids revealed marked alterations in phosphatidylcholine and cardiolipin leading to a decreased 20:4/18:2 ratio. The functional and structural alterations of the liver mitochondria from chronically treated rats remained unaffected for at least 2 weeks after cessation of TAA application.