Resveratrol Alleviates Cadmium-Induced Damage and Overexpression of Epidermal Growth Factor Receptor and its Downstream Signaling Proteins in the Reproductive System of Male Swiss Albino Mice

Abstract

Nowadays, exposure to heavy metals and their detrimental effects in humans are grave health concerns. In this study, we investigated the protective effect of resveratrol (RES) against CdCl2 (cadmium chloride)-induced impairment of spermatogenesis, histopathological alterations, and the up-regulation of epidermal growth factor receptor (EGFR) signaling cascade in Swiss albino mice. Two different doses of CdCl2 were injected intraperitoneally into two groups of mice, and in the third group RES was administered orally before injecting CdCl2 (3 times/wk) for 14 days. Sperm motility, count, vitality, and morphology were analyzed. Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and western blot analyses were performed on testis tissue. In CdCl2-administered animals, significant perturbations of spermatogenesis and histoarchitecture of seminiferous tubules were observed. p-EGFR, p-AKT, AKT1/2/3, NF-κβ (p50), and COX-2 of the EGFR cascade were up-regulated. Although there was significant negative correlation between percentage of motile cells and protein expression, we found positive correlation between morphologically abnormal cells and overexpression of proteins in CdCl2-only treated groups. Marked improvement of sperm parameters and histopathological damages as well as down-regulation of the EGFR signaling cascade were observed in the RES-pretreated mice. Hence, the present study elucidates that RES protects against CdCl2-induced perturbation of spermatogenesis and overexpression of EGFR and its downstream signaling proteins.

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

“…In particular, Re showed a protective action against testicular toxicity as it upregulated Bcl2, downregulated p53 and Bax gene expression [ 20 , 54 ], and reduced inflammatory cascade [ 54 ]. Furthermore, marked improvements in sperm parameters and histopathological damages were observed in the Re-pretreated mice [ 34 ]. Indeed, our study confirmed the positive role of Re in Cd-challenged animals on both biochemical and structural parameters.…”

“…Additionally, resveratrol (Re), a polyphenol present in many plants and especially in red wine, showed antioxidant properties [ 30 ] as well a positive regulation of apoptosis and other zonula occludens protein expression, such as occludin [ 31 , 32 ]. In the testis, Re protected from oxidative stress [ 33 ], partially reversed the dysregulation of the apoptotic pathways [ 20 ], and improved sperm parameters and histopathological damage [ 34 ]. Recently, bergamot juice (BJ), obtained from the endocarp of Citrus bergamia Risso et Poiteau (bergamot) fruits, gained the attention of pharmaceutical companies interested in natural products and antioxidant bioactive compounds from dietary sources [ 35 , 36 , 37 ].…”

Cadmium as a testicular toxicant: A Review

“…Resveratrol‐mediated reversal of Cd‐induced testicular damage has been observed in rats, where administration of resveratrol (20 mg/kg bw) before or after Cd improved semen parameters, enhanced the concentration of serum gonadotropins, and reduced the lipid peroxidation in the testis (Eleawa et al, 2014). Pretreatment with resveratrol (10 mg/kg bw) significantly improved the various parameters of sperm, histological damage, as well as downregulation of the epidermal growth factor receptor signaling cascade in mice testis (Mitra et al, 2016). The ameliorative effect of grape seed extract (GSE), a powerful antioxidant containing high levels of vitamins C and E, was evaluated against CdCl 2 ‐induced dysfunctioning in rat testis.…”

A Critical Assessment of the Therapeutic Potential of Resveratrol Supplements for Treating Mitochondrial Disorders

“…[ 36 ]. In vivo experiments showed that RSV also protected against Cd-induced perturbations of spermatogenesis and histology in mice [ 37 ].…”