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.
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.
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Sreyashi
S
Mitra
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Sayantan
S
Bhattacharyya
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Sudipta
S
Ray
Department of Life Science & Bioinformatics, Assam University, Silchar, India.
Rinku
R
Saha
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Paramita
P
Ghosh
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Sanchita
S
Rauth
Department of Epidemiology and Biostatistics, Chittaranjan National Cancer Institute, Kolkata, India.
Syamsundar
S
Mandal
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Samir
S
Banerjee
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, India.
Nabendu
N
Murmu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D000077185:Resveratrol; D012661:Semen / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects
D000975:Antioxidants; D004785:Environmental Pollutants; D047908:Intracellular Signaling Peptides and Proteins; D013267:Stilbenes; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D019256:Cadmium Chloride; D000077185:Resveratrol