POTENTIAL PROTECTIVE EFFECT OF APOCYNIN IN ETHYLENE GLYCOL-INDUCED HEPATIC DAMAGE BY ATTENUATION OF MITOCHONDRIAL OXIDATIVE STRESS

ABSTRACTObjective: The present study was carried out to investigate the protective role of apocynin (APO), an nicotinamide adenine dinucleotide phosphateoxidase inhibitor, against ethylene glycol (EG)-induced hepatotoxicity in rats.Methods: Male Sprague-Dawley rats were divided into three groups with six animals in each group. Control group; EG group, in which hyperoxaluriawas induced by 0.4% EG in drinking water for 9 days; and EG+APO group, 0.4% EG in drinking water for 9 days along with APO at a dosage of200 mg/kg body weight/day, intraperitoneal. All the experimental animals were sacrificed on day 10. Serum and the liver homogenates were analyzedfor various biochemical parameters. Mitochondria from liver were isolated by differential centrifugation and were diagnosed for vital biochemicalparameters.Results: Hyperoxaluric animals have shown significantly increased levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvictransaminase, alkaline phosphatase, and lactate dehydrogenase, thus suggesting liver dysfunction. Declined activities of respiratory chain enzymesshowed mitochondrial dysfunction in EG treated rats. In addition, mitochondrial oxidative stress was evident by decreased levels of superoxidedismutase, reduced glutathione, and an increased lipid peroxidation (LPO). APO (200 mg/kg/day), significantly decreased EG-induced oxidativestress by reducing LPO and restoring antioxidant enzymes activities in liver tissue. Also, reduction in the impairment of liver mitochondria functioningwas detected in APO treated rats. Histological analysis depicted that APO treatment decreased liver epithelial damage, increased Kupffer cells, andrestored normal hepatocyte morphology.Conclusion: The results demonstrated the potential beneficial effects of APO in reducing EG-induced liver damage that might be through attenuationof mitochondrial oxidative stress.Keywords: Ethylene glycol, Liver, Oxidative stress, Mitochondrion, Apocynin, Antioxidant