Intravenous Mitochondrial Injection Attenuates Methanol-Induced Cardiotoxicity Through Restoration of Mitochondrial Function and Suppression of Oxidative Stress.

Methanol poisoning induces severe mitochondrial dysfunction through inhibition of mitochondrial respiration, excessive reactive oxygen species (ROS) generation and oxidative stress. The present study investigated whether injection of freshly isolated mitochondria, could attenuate methanol-induced cardiac mitochondrial dysfunction and oxidative damage in rat. Adult male Wistar rats were randomly allocated into five experimental groups: control, methanol, methanol plus single mitochondrial injection, methanol plus repeated mitochondrial injection (double) and mitochondria alone. Fresh functional mitochondria were isolated from healthy donor cardiac tissue and administered intravenously (250 µg/kg), 30 min after methanol intoxication. Serum cardiac injury biomarkers, including creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), were measured. Oxidative stress was evaluated by determining malondialdehyde (MDA) and glutathione (GSH) levels. Cardiac mitochondrial function was assessed by measuring succinate dehydrogenase (SDH) activity, mitochondrial swelling, mitochondrial ROS production, and mitochondrial membrane potential (MMP). Methanol intoxication significantly increased serum cardiac injury biomarkers, ROS generation, lipid peroxidation, and mitochondrial swelling while markedly reducing GSH content, SDH activity, and MMP compared with the control group. Mitochondrial injection significantly attenuated oxidative stress, decreased ROS production, restored antioxidant capacity, improved SDH activity, reduced mitochondrial swelling, and preserved MMP. Repeated mitochondrial administration showed relatively greater improvement than single administration, although no consistent dose-response relationship was observed. Also, histopathological examinations demonstrated significant recovery following mitochondrial injection. Fresh mitochondrial injection effectively ameliorated methanol-induced cardiotoxicity by reducing oxidative stress, preserving mitochondrial integrity, and restoring mitochondrial function in cardiac tissue. These findings suggest that mitochondrial injection represents a promising mitochondria-targeted therapeutic approach for methanol-induced cardiotoxicity.