Alcohol-Induced Mitochondrial and NADPH Oxidase Mediated ROS Generation Alter Neuroendocrine Status: Role of Pterocarpus Santalinus

Abstract

The association between oxidative stress and endocrine status with respect to the role of Pterocarpus santalinus (PSE) against alcohol-induced neurotoxicity in rats was investigated. Male albino rats were divided into, control, alcohol treated, alcohol + PSE treated, and PSE treated group. Twenty percent of ethanol (5g/kg body weight/day) was given with and without PSE (250 mg/kg body weight/day) for 60 days. Decreased plasma testosterone, estradiol, thyroid hormones (T3 and T4), and increased cortisol concentrations in alcohol treated rats were observed. Besides, elevated lipid peroxidation, protein carbonyls, NADPH oxidase (NOX), and cytochrome P-450 (CYP-450) activities, with mitochondrial dysfunction were noticed. Moreover, increased protein expression of the phosphorylated protein kinase C (p-PKC), phospholipase C (p-PLC), and NOX2 with decreased antioxidant status was also noticed in alcohol ingested rats. Administration of PSE to alcohol treated rats reduced oxidative stress by increasing antioxidant status, also modulated mitochondrial dysfunction and protein expression of p-PKC, p-PLC and NOX2. In conclusion, ROS generated via mitochondrial dysfunction causes activation of NOX activity through PLC and PKC dependent pathways leading to more ROS generation, which in turn alters the circulating hormonal levels. The phytocompounds present in PSE confer therapeutic efficacy by scavenging ROS and thereby offer protection.