The potential gonadoprotective effects of grape seed extract against the histopathological alterations elicited in an animal model of cadmium-induced testicular toxicity

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 4 equal groups; negative control, cadmium (5 mg/k/day), grape seed extract (100 mg/k/day), and cadmium + GSE. Testicular weights were measured. Hematoxylin & 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. 2 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 edema and mononuclear cell infiltrations. No remarkable changes were observed in the grape-seed-only group when compared to the control group. In both combined 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: GSE protected against cadmium-induced testicular toxicity in rats, reducing induced histopathological changes, and maintaining testicular histoarchitecture.National Institutes of Health [9]. Whenever possible, the procedures in the current study were conducted to avoid or minimize suffering, distress, and pain to animals. DrugsCadmium, in the form of cadmium chloride (CdCl2, 96% pure), was purchased from Sigma-Aldrich Corporation of industrial chemistry and biotechnology (St. Louis, Missouri, USA). Grape seed extract was purchased from herbal and medicinal plant store, Benha governorate, Egypt. The drugs were dissolved in normal saline. Experimental designThe rats were randomly divided into four groups, eight rats each: -Group 1: Negative control group (normal saline was given daily for 30 days by gastric gavage)Group 2: The animals were given grape seed extract (100 mg/kg/d) dissolved in normal saline for 30 days by gastric gavage [32]. A concentration of 100 mg was dissolved in 10 ml normal saline and shook to obtain a solution of 10 mg/ml. Group 3:The animals were given cadmium (5mg/kg/d) dissolved in normal saline for 30 days by gastric gavage [14]. A concentration of 5mg was dissolved in 10 ml normal saline and shook to obtain a solution of 0.5 mg/ml. Group 4:The animals were given cadmium (5mg/kg/d) + grape seed extract (100 mg/kg/d) for 30 days by gastric gavage.In order to avoid possible drug interactions and drug absorption, the drugs were given in the same time of the day, in two different time intervals. Cadmium was given in the morning (10 AM) whil...

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“…The scrotal testes showed +ve PCNA immunostained cells, mainly in the early stages of the spermatogenic cells and weak or absent PCNA immunostaining in the late stages. It was reported that the testicular tissues obtained from rats treated with cadmium had a harmful effect on the testis through its oxidative stress activity [27]. This was supported by Dutta et al [12] who proved that oxidative stress ameliorate the proliferation and induces apoptosis in the highly differentiated spermatogenic cells causing its degeneration in the order of; sperms, spermatids, spermatocytes then spermatogonia.…”

Natural Products as Protective Agents for Male Fertility

“…Several studies have identified grape seed extract, grape seed pro-anthocyanidin extract, and grape juice concentrate as protective factors against cadmium toxicity. Grape seed extract and grape seed pro-anthocyanidin extract improved histopathological find-ings [132][133][134][135], increasing the diameter and normal SeT [132,135], testicular weight [132], and Johnsen's mean testicular biopsy score and decreasing the apoptotic index [135]. It was also observed to increase PCNA immunoreactivity [132] and total antioxidant status (TAS) [133] in the enzymes of the antioxidant defense system and genes associated with steroidogenesis and Ki-67 expression [134], and it decreased MDA levels [133,134] and the immunoreactivity of the apoptotic regulator Bax [134].…”

“…Grape seed extract and grape seed pro-anthocyanidin extract improved histopathological find-ings [132][133][134][135], increasing the diameter and normal SeT [132,135], testicular weight [132], and Johnsen's mean testicular biopsy score and decreasing the apoptotic index [135]. It was also observed to increase PCNA immunoreactivity [132] and total antioxidant status (TAS) [133] in the enzymes of the antioxidant defense system and genes associated with steroidogenesis and Ki-67 expression [134], and it decreased MDA levels [133,134] and the immunoreactivity of the apoptotic regulator Bax [134]. Grape juice concentrate treatment against cadmium toxicity demonstrated that co-administration restored the testis, epididymis, and ventral prostate weight [136] to normal levels, ameliorating tissue architecture [125,136,137], epididymis epithelium height (caput and cauda regions) [125] and improving sperm parameters such as production, counts, transit time [125], and morphology [136].…”