Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats

Maloos Naderi, Nematollah Ahangar, Faezeh Badakhshan, Maryam Ghasemi, Fatemeh Shaki, Maloos Naderi, Nematollah Ahangar, Faezeh Badakhshan, Maryam Ghasemi, Fatemeh Shaki

Abstract

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Keywords: Oxidative stress; Selenium; Testis toxicity; Valproic acid; Zinc.

Conflict of interest statement

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Effects of Selenium (Se) and Zinc (Zn) on valproic acid (VPA)-induced lipid peroxidation in testis tissue. Data were expressed as mean. NS, normal salin (control group); Vit E, vitamin E. *P<0.05 compared to control. ***P<0.001 compared to control. #P<0.05 compared to VPA (500 mg/kg). ###P<0.001 compared to VPA (500 mg/kg).
Fig. 2
Fig. 2
Effects of Selenium (Se) and Zinc (Zn) on valproic acid (VPA)-induced protein carbonyl in testis tissue. Data were expressed as mean. NS, normal salin (control group); Vit E, vitamin E. **P<0.01 compared to control. ***P<0.001 compared to control. #P<0.05 compared to VPA (500 mg/kg). ###P<0.001 compared to VPA (500 mg/kg).
Fig. 3
Fig. 3
Effects of Selenium (Se) and Zinc (Zn) on valproic acid (VPA)-induced GSH oxidation in testis tissue. Data were expressed as mean. NS, normal salin; Vit E, vitamin E. *P<0.05 compared to control. ***P<0.001 compared to control. ###P<0.001 compared to VPA (500 mg/kg).
Fig. 4
Fig. 4
H&E-stained testis histology pictures (with ×40 objective lens) showing normal testis. Morphology (control) (A), VPA-treated groups showed a decrease in germinal cell layer thickness (B), degenerative. changes and vacuolization in germinal cells (C), impaired spermatogenesis, stop maturation in some parts (D), increase in leydig cells (E). VPA+Zn-treated group (F), and VPA+Se-treated group (G) showed a normal germinal cell layer thickness and improve maturation. (H) VPA+Zn+Se-treated groups (combination therapy) showed better effect than Zn and Se alone. VPA, valproic acid; Zn, zinc; Se, selenium.

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