Acrolein-induced toxicity - Defective mitochondrial function as a possiblemechanism

Administration of acrolein (2.5 mg/kg body weight/day) to rats for 45 days depleted the glutathione level in liver, which triggered an imbalance in th e antioxidant defense, resulting in lipid peroxidation, Enhanced lipid pero xidation damaged the membranous structure of mitochondria, which was indica ted by the loss of lamellae, and increased the oxidation of exogenously add ed NADH. Loss in membrane integrity altered the activities of the tricarbox ylic acid cycle enzymes and levels of cytochromes. Decreased rate of ADP-st imulated oxygen uptake, respiratory coupling ratio, and ATP synthesis-were also observed. We report that the acrolein-induced toxicity is mediated thr ough the depletion of GSH leading to impairment of rat liver mitochondrial function.