NEPHROPROTECTIVE POTENTIAL OF GREEN TEA EXTRACT AND HESPERETIN IN HEAT STRESS INDUCED EXPERIMENTAL NEPHROPATHY

Heat stress disrupts the delicate thermoregulatory setup of human body, activating various molecular pathways (reduction in uric acid production via polyol-fructokinase pathway, elevated levels of reactive oxygen species (ROS) causing oxidative stress, intracellular calcium overload associated with mitochondrial dysfunction, and diminished nitric oxide (NO) causing vascular endothelial injury) that contribute towards Heat Stress Nephropathy (HSN).This study was designed to investigate the nephroprotective potential of Green Tea Extract (GTE) and Hesperetin (HES) in HSN. Mice subjected to heat stress (39.5^oC for 30 minutes, twice a day for 10 days) along with 2, 4-Dinitrophenol (DNP) were used as a nephropathy model. Furthermore, pretreatment with GTE (50mg/kg; s.c) and HES (50mg/kg; s.c) were done simultaneously followed by heat stress procedure. Results demonstrated a significant improvement in kidney function, as evidenced by reduced levels of Blood Urea Nitrogen (BUN) and Serum Creatinine (sCr) in mice pre-treated with GTE and HES compared to heat- stressed animals. Moreover, this combination led to a decrease in Thiobarbituric reactive substances (TBARS) levels while enhancing Superoxide dismutase (SOD) and Glutathione (GSH) levels. Histopathological examinations confirmed a reduction in nephronal damage. In conclusion, the nephroprotection shown by this combination were attributed to increased expression of endothelial nitric oxide synthase (eNOS), reduced calcium overload, and lowered ROS production, and may be a good candidate for future preclinical as well as clinical nephrological researches.