The potential gonadoprotective effects of grape seed extract against the histopathological alterations elicited in an animal model of cadmium-induced testicular toxicity
, 2, 3
Abstract
Background: Grape seed extract (GSE) is a powerful antioxidant containing high levels of bioflavonoids, vitamin C and vitamin E. The aim of the work is to study the possible protective and ameliorative effects of grape seed extract in an animal model of cadmium (Cd)-induced testicular toxicity in rats.
Materials and methods: A thirty-day oral gavage study in adult male albino rats was performed using 32 animals, randomly divided into four equal groups; negative control, Cd (5 mg/k/day), GSE (100 mg/k/day), and Cd + GSE. Testicular weights were measured. Haematoxylin and eosin (H&E) staining and proliferating nuclear cell antigen (PCNA) immunohistochemistry, as a marker for proliferation were done. Morphometric parameters were assessed and subjected to statistical analysis.
Results: The H&E results showed atrophy and distortion of the seminiferous tubules (STs) with sloughing of the spermatogenic epithelium in cadmium group. The interstitial spaces were widened and showed oedema and mononuclear cell infiltrations. No remarkable changes were observed in the GSE-only group when compared to the control group. In Cd + GSE group, maintaining of the STs and their lining cells was evident. The immunohistochemical results showed marked positive PCNA immunoreactivity in both control and GSE groups, while negative immunoreaction was noticed in Cd group. Limited positive PCNA immunoreactivity was ameliorated in Cd + GSE group.
Conclusions: Grape seed extract protected against cadmium-induced testicular toxicity in rats, reducing induced histopathological changes, and maintaining testicular histoarchitecture.
Keywords: cadmiumgrape seed extracttestisseminiferous tubulesproliferating nuclear cell antigen
References
- Adamkovičová M, Toman R, Cabaj M. Diazinon and cadmium acute testicular toxicity in rats examined by histological and morphometrical methods. 2010; 2010(3): 134–140.
- Alkhedaide A, Alshehri ZS, Sabry A, et al. Protective effect of grape seed extract against cadmium-induced testicular dysfunction. Mol Med Rep. 2016; 13(4): 3101–3109.
- Amara S, Abdelmelek H, Garrel C, et al. Preventive effect of zinc against cadmium-induced oxidative stress in the rat testis. J Reprod Dev. 2008; 54(2): 129–134.
- Faroon O, Ashizawa A, Wrigh S, et al. Toxicological Profile for Cadmium. U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA. ; 2012.
- Bancroft JD, Lyton C. The Hematoxylins and Eosin. In: Suvarna SK, eds. Theory and Practice of Histological Techniques. 8th ed. 2018: 126–138.
- Bernhoft RA. Cadmium toxicity and treatment. Sci World J. 2013; 2013: 394652.
- Blanco A, Moyano R, Vivo J, et al. Quantitative changes in the testicular structure in mice exposed to low doses of cadmium. Environ Toxicol Pharmacol. 2007; 23(1): 96–101.
- Burukoğlu D, Bayçu C. Protective effects of zinc on testes of cadmium-treated rats. Bull Environ Contam Toxicol. 2008; 81(6): 521–524.
- Committee NRC. Guide for the Care and Use of Laboratory Animals: NIH Publications No. 8023. 8th ed. National Academies Press; 2010; 1-220.
- de Souza Predes F, Diamante MA, Dolder H. Testis response to low doses of cadmium in Wistar rats. Int J Exp Pathol. 2010; 91(2): 125–131.
- El-Beshbishy H, Mohamadin A, Abdel-Naim A. In Vitro Evaluation of the Antioxidant Activities of Grape Seed (Vitis vinifera) Extract, Blackseed (Nigella sativa) Extract and Curcumin. J Taibah Univ Med Sci. 2009; 4(1): 23–35.
- El-Refaiy AI, Eissa FI. Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents. Saudi J Biol Sci. 2013; 20(3): 265–280.
- El-Shahat AR, Gabr A, Meki AR, et al. Altered Testicular Morphology and Oxidative Stress Induced by Cadmium in Experimental Rats and Protective Effect of Simultaneous Green Tea Extract. Int J Morphol. 2009; 27(3).
- Evcimen M, Demirel HH, Aslan R, et al. For rats which are implemented cadmium chloride exposure, polydatin and grape seed extracts protective effcts on testis and brain tissues. Glob J Res Anal. 2015; 4(10): 307–310.
- Filippini T, Cilloni S, Malavolti M, et al. Dietary intake of cadmium, chromium, copper, manganese, selenium and zinc in a Northern Italy community. J Trace Elem Med Biol. 2018; 50: 508–517.
- Godt J, Scheidig F, Grosse-Siestrup C, et al. The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol. 2006; 1: 22.
- Huang Y, He C, Shen C, et al. Toxicity of cadmium and its health risks from leafy vegetable consumption. Food Funct. 2017; 8(4): 1373–1401.
- Jia Z, Song Z, Zhao Y, et al. Grape seed proanthocyanidin extract protects human lens epithelial cells from oxidative stress via reducing NF-small ka, CyrillicB and MAPK protein expression. Molecuar Vis. 2011; 17: 210–217.
- Juríková M, Danihel Ľ, Polák Š, et al. Ki67, PCNA, and MCM proteins: Markers of proliferation in the diagnosis of breast cancer. Acta Histochem. 2016; 118(5): 544–552.
- Kappagoda CT, Burton-Freeman B, Edirisinghe I. Modulation of oxidative stress, inflammation, and impaired insulin sensitivity with grape seed extract. June. 2017: June.
- Kaur M, Agarwal C, Agarwal R. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products. J Nutr. 2009; 139(9): 1806S–1812S.
- Kiernan JA. Immunohistochemistry. In: Kiernan J, ed. Histological and Histochemical Methods. Theory and Practice. 4th ed. Scion Publishing Ltd 2015: 454–490.
- Mandic A, Đilas S, Ćetković G, et al. Polyphenolic Composition and Antioxidant Activities of Grape Seed Extract. Int J Food Prop. 2008; 11(4): 713–726.
- Narges K, Tavakkoli L. Environmental and occupational exposure to cadmium in Iran: a systematic review. Rev Environ Health. 2016; 31(4): 457–463.
- Onwuka FC, Erhabor O, Eteng MU, et al. Ameliorative effect of cabbage extract on cadmium- induced changes on hematology and biochemical parameters of albino rats. J Toxicol Environ Heal Sci. 2010; 2(2): 11–16.
- Pires VC, Gollücke AP, Ribeiro DA, et al. Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: a chronic assay. Br J Nutr. 2013; 110(11): 2020–2029.
- Prozialeck WC, Edwards JR, Nebert DW, et al. The vascular system as a target of metal toxicity. Toxicol Sci. 2008; 102(2): 207–218.
- Rahimzadeh MR, Rahimzadeh MR, Kazemi S, et al. Cadmium toxicity and treatment: An update. Casp J Intern Med. 2017; 8(3): 135.
- Sano A. Safety assessment of 4-week oral intake of proanthocyanidin-rich grape seed extract in healthy subjects. Food Chem Toxicol. 2017; 108(Pt B): 519–523.
- Sehirli O, Ozel Y, Dulundu E, et al. Grape seed extract treatment reduces hepatic ischemia-reperfusion injury in rats. Phytother Res. 2008; 22(1): 43–48.
- Siu ER, Mruk DD, Porto CS, et al. Cadmium-induced testicular injury. Toxicol Appl Pharmacol. 2009; 238(3): 240–249.
- Sönmez MF, Tascioglu S. Protective effects of grape seed extract on cadmium-induced testicular damage, apoptosis, and endothelial nitric oxide synthases expression in rats. Toxicol Ind Health. 2016; 32(8): 1486–1494.
- Terra X, Pallarés V, Ardèvol A, et al. Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. J Nutr Biochem. 2011; 22(4): 380–387.
- Wang L, Xu T, Lei W, et al. Cadmium-induced oxidative stress and apoptotic changes in the testis of freshwater crab, Sinopotamon henanense. PLoS One. 2011; 6(11).
- WHO. Exposure to Cadmium: A Major Public Health Concern; 2010.
- Xu X, Nie S, Ding H, et al. Environmental pollution and kidney diseases. Nat Rev Nephrol. 2018; 14(5): 313–324.
