Forskolin ameliorates mancozeb‐induced testicular and epididymal toxicity in Wistar rats by reducing oxidative toxicity and by stimulating steroidogenesis

Abstract

In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb-induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo-osmotic swelling-tail swelled sperm was observed in mancozeb-treated rats. The activity levels of testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase and circulatory testosterone levels were significantly decreased in mancozeb-treated rats. Exposure to mancozeb resulted in a significant decrease in glutathione levels and superoxide dismutase and catalase activity levels with an increase in lipid peroxidation levels in the testes and epididymis. Coadministration of forskolin mitigated the mancozeb-induced oxidative toxicity and suppressed steroidogenesis and spermatogenesis.

Mancozeb induces testicular dysfunction through oxidative stress and apoptosis: Protective role of N-acetylcysteine antioxidant

“…It is widely utilized for the control of a wide range of diseases in agricultural, horticultural, and ornamental crops. Several studies have shown that exposure to MZB can cause complications, including neurotoxicity (Bailey et al, 2016;Domico et al, 2006;Erro et al, 2011), carcinogenicity (Belpoggi et al, 2002), genotoxicity (Srivastava et al, 2012(Srivastava et al, , 2016, and reproductive toxicity (Bindali and Kaliwal, 2002;Iorio et al, 2015;Joshi et al, 2005;Kackar et al, 1997;Runkle et al, 2017;Girish and Reddy, 2018), which might lead to various degrees of infertility.…”

“…Exogenous sources include radiation, smoking, alcohol consumption, and environmental toxins such as pesticides (Agarwal et al, 2014). The production of ROS and induction of oxidative stress have been reported as the most probable mechanism of MZB neurotoxicity (Bailey et al, 2016; Domico et al, 2007), cytotoxicity of human colon (Hoffman et al, 2016), testicular and epididymal toxicity in rats (Girish and Reddy, 2018). In addition, MZB induces oxidative stress inovarian granulosa cell lines (Iorio et al, 2015) and oocytes in mice (Liu et al, 2017).…”

Cytotoxicity of mancozeb on Sertoli–germ cell co-culture system: Role of MAPK signaling pathway

“…Many previous studies have also reported adverse health effects of MZB in experimental mammals such as hepatotoxicity (Saber et al, 2019;Yahia et al, 2019), carcinogenic potential (Belpoggi et al, 2002), neurotoxicity and Parkinson-like symptoms (Domico et al, 2007), dysfunction of thyroid glands (Axelstad et al, 2011), nephrotoxicity, endocrine system disruption in females, and defects in fetal development (Bianchi et al, 2020;Girish and Reddy, 2017;Liu et al, 2017). Male reproductive system disorders such as infertility and spermatogenesis insufficiency has been reported previously.…”

Multi Species Analyses Reveal Testicular T3 Metabolism and Signalling as a Target of Environmental Pesticides

“…We analyzed the effects of the exposure, in vivo, in evolutionary distant vertebrates and in ex-vivo cultures of murine seminiferous tubules trying to reproduce in terms of dose and exposure window a scenario relevant to humans. Although in different experimental settings, previous results evidence that CPF and ETU exposure may cause degeneration of seminiferous tubules, exert a negative effect on sexual hormones levels, alter the expression of steroidogenic enzymes, and, finally, impair sperm production [ 68 , 69 , 70 ]. The here reported alteration of serum testosterone level and of steroidogenic enzymes expression ( Figure 1 B,C) agrees with previously published data [ 68 , 69 , 70 ].…”

“…Although in different experimental settings, previous results evidence that CPF and ETU exposure may cause degeneration of seminiferous tubules, exert a negative effect on sexual hormones levels, alter the expression of steroidogenic enzymes, and, finally, impair sperm production [ 68 , 69 , 70 ]. The here reported alteration of serum testosterone level and of steroidogenic enzymes expression ( Figure 1 B,C) agrees with previously published data [ 68 , 69 , 70 ]. Vice versa, the effect at CPF-H treatment is not in line with them.…”