Epigallocatechin gallate exacerbates fluoride-induced oxidative stress mediated testicular toxicity in rats through the activation of Nrf2 signaling pathway

Abstract

Objective: To explore the ameliorative potential of Epigallocatechin gallate (EGCG) by evaluating markers of oxidative stress, apoptosis, and inflammation and antioxidant competence in Fl intoxicated rats. Methods: The animals were divided in to four groups that is control, EGCG alone, NaF, and EGCG with NaF. Group III animal were exposed to Fl as sodium Fluoride (NaF) (25 mg/kg BW) for 4 weeks. After the completion of the treatment, the testis tissues has been removed and used for the experimental observations. Results: Pre-administration of EGCG to Fl intoxicated rats showed a significant normalization in the levels of steroidogenic enzymes, testosterone, sperm functions, oxidative stress markers and antioxidant status. The altered levels of proinflammatory cytokines and apoptotic markers were also relapsed in close proximity to control. In addition, EGCG significantly improved antioxidant status and reduced the oxidative stress and pathological changes in testes. The mRNA and protein analysis also substantiated that EGCG pre-treatment markedly enhanced the expression of Nrf2 and its target genes HO-1, NQO1 and γGCS and suppressed the expression of Keap1 in testis. Conclusion: Altogether, our findings supports that EGCG attenuates Fl toxicity in testis through Nrf2 activation.

Keywords

• Fluoride
• EGCG
• Testes
• Oxidative stress
• Inflammation
• Apoptosis
• Nrf2