Biochemical state of brain-liver axis of rats under restraint-induced stress and 2-oxoglutarate impact

Abstract

Environmental factors play a significant role in affecting the overall health of organisms, with stress being a notable contributor. The process of urbanization and globalization in modern society introduces additional stressors, exacerbating population health issues. Consequently, there is a need for thorough examination, analysis, and exploration of strategies to mitigate the adverse effects of stress. 2-Oxoglutarate, an essential intracellular metabolite and mediator with metabolite trophic properties, emerges as a promising candidate for intervention. In this study, we aimed to evaluate the combined impact of restraint-induced stress and 2-oxoglutarate on the oxidative-reducing balance, antioxidant system effectiveness, and the functional status of the liver and brain in rats. Restraint-induced stress was found to elevate oxidative stress levels, as evidenced by increased concentrations of malonic dialdehyde and oxidative-modified proteins, particularly in the brain. Additionally, signs of lactic acidosis were observed in the liver, indicating physiological changes in response to stress. Furthermore, restraint-induced stress significantly altered bioenergy components, with decreased superoxide dismutase activity and increased cytochrome C concentration, potentially indicating mitochondrial dysfunction and increased membrane permeability. The incorporation of a 2% solution of 2-oxoglutarate into the diet demonstrated a reduction in malonic dialdehyde and carbonylated protein formation, leading to more effective restoration of oxidative-reducing balance in the brain compared to the liver. Additionally, normalization of the lactate/pyruvate concentration ratio and decreased lactate dehydrogenase activity, alongside elevated alanine aminotransferase levels, suggested a decrease in oxidative stress in the liver. Moreover, exogenous 2-oxoglutarate exhibited a positive effect on superoxide dismutase activity and cytochrome C concentration, indicating a reduction in oxidative tension in the liver and progressive mitochondrial function recovery. Based on these findings, exogenous 2-oxoglutarate emerges as a promising metabolitotrope and adaptogen for managing oxidative stress and improving mitochondrial function.