Impacts of n‐acetyl cysteine on gibberellic acid‐induced testicular dysfunction through regulation of inflammatory cytokines, steroid and antioxidant activity

Abstract

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n‐acetyl cysteine (NAC, 150 mg/kg bw) co‐administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty‐four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co‐administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3‐treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3‐treated rats, an overexpression of the inflammatory cytokines (TNF‐α, IL‐1β) and anti‐inflammatory cytokine IL‐10 with boost mRNA expression of nuclear factor‐kappa (NFkB) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3‐treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3β‐HSD) and downregulated the pro‐inflammatory cytokines mRNA expression (TNF‐α, IL‐1β). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro‐inflammatory cytokines mRNA expression.

Chrysin abrogates gibberellic acid‐induced testicular oxidative stress and dysfunction via the regulation of antioxidants and steroidogenesis‐ and apoptosis‐associated genes

“…Our data are in agreement with those of other studies (Soliman et al, 2021b) that revealed a decrease in the activity of antioxidants in adult rats (Khalaf et al, 2019). GSH and SOD are oxidative stress biomarkers that are required for testes integrity (H. Yang et al, 2011).…”

“…In the testes of rats, GA3 has been reported to cause DNA damage and oxidative stress (Sayed et al, 2020;Soliman et al, 2009;Soliman et al, 2021a;Soliman et al, 2021b). The use of GA3 for an extended period of time reduced antioxidant enzyme activity and elevated oxidative stress.…”

“…GA3 treatment in rats decreased hepatic carbohydrates, total protein content, and liver biomarkers in the serum, as well as alkaline phosphatase (Hussein et al, 2011; Muthu et al, 2011). In the testes of rats, GA3 has been reported to cause DNA damage and oxidative stress (Sayed et al, 2020; Soliman et al, 2009; Soliman et al, 2021a; Soliman et al, 2021b). The use of GA3 for an extended period of time reduced antioxidant enzyme activity and elevated oxidative stress.…”

Gibberellic acid‐induced hepatorenal dysfunction and oxidative stress: Mitigation by quercetin through modulation of antioxidant, anti‐inflammatory, and antiapoptotic activities

“…QR possesses both direct and indirect antioxidant mechanisms(Costa et al, 2016). Our data are consistent with those ofSoliman et al (2021), confirming overexpression of inflammatory cytokines (TNFα, IL-1β), reduced expression of anti-inflammatory cytokine IL-10 in GA3-treated rats, and increased mRNA expression of NF-κB. All were normalized in the group cotreated with QR +GA3.…”

“…The control group (CNT) received saline; the quercetin group (QR) received 50 mg/kg/BW quercetin dissolved in saline via daily intraperitoneal (i.p.) injection for 4 weeks (Al-Otaibi et al, 2018;Bo et al, 2018); the gibberellic acid group (GA3) received 55 mg/kg/ BW GA3 via daily oral gavage for 4 weeks (Lafi et al, 2018;Soliman et al, 2021); and the protective group (QR +GA3) was maintained under experimental settings (Alsemeh et al, 2019a(Alsemeh et al, , 2019b, injected with QR and gavaged with GA3 at the same doses as those used in the QR and GA3 groups. Quercetin was injected an hour before GA3 administration to confirm its protective effects.…”