Epigallocatechin-gallate attenuates rapamycin exacerbated high fat diet-induced autophagy, hormonal dysregulation, testicular and brain oxidative stress, and neurochemical changes in rats

Abstract

This study investigated whether epigallocatechin-gallate (EGCG) could counteract the detrimental effects of high-fat diet (HFD)-induced obesity in rats exposed to rapamycin-induced reproductive and neuronal changes. Six rats per treatment group (n = 6) were utilized, in which groups 1 and 2 had dimethylsulfoxide (DMSO) (0.1%) and EGCG (80 mg/kg) respectively. Group 3 received HFD + 0.1% DMSO daily for 56 days. Group 4 received HFD + rapamycin (1 mg/kg) orally for 56 days. Rats in group 5 received HFD for 56 days and EGCG (80 mg/kg, p.o.) from days 29–56. Group 6 received the combination of HFD + rapamycin (56 days) with EGCG (80 mg/kg) from days 29–56. Cognitive loss was assessed using Y-maze-test (YMT). Afterwards, serum sex hormones, insulin-glucose balance, serotonin concentration, acetylcholinesterase activity, sperm features, antioxidants, and the markers of oxido-nitrergic, autophagy and apoptotic mediators were assessed. EGCG reversed rapamycin exacerbated HFD-induced alterations in spermatogenesis, insulin-glucose balance, reproductive hormones, oxido-nitrergic stress, and altered serotonin, acetylcholinesterase levels, and autophagic and apoptotic activities in rats' testes and brains respectively. EGCG significantly attenuated HFD-induced cognitive loss. The study showed that EGCG attenuated rapamycin-mediated HFD-induced spermatogenesis deficiency and cognitive impairment via normalization of reproductive hormones, testicular and brain oxidative stress, apoptotic, autophagic activities, with serotonin and cholinergic levels in rats.