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

Abstract

Mancozeb (MZB) is one of the fungicides used in pest control programs that might affect human health including reproductive system. The aim of this study was to demonstrate the mechanisms through which MZB induces testicular tissue damage and the probable protective effect of N-acetylcysteine (NAC), a modified amino acid, with antioxidant property, against MZB toxicity in an animal model. Male albino mice ( n = 8) were exposed to different doses of MZB (250 and 500 mg/kg/day) by oral gavage without or with NAC (200 mg/kg, twice/week) for 40 days. Sub-chronic MZB dose-dependently decreased sperm motility and count. Exposure to MZB increased lipid peroxidation and protein carbonyl, while it reduced antioxidant enzymes activities, total antioxidant capacity, and glutathione content. The histopathological examination clearly showed deleterious changes in the testicular structure. At the molecular levels, the results of quantitative real time-poly chain reaction (qRT-PCR) showed that MZB upregulated oxidative stress markers inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX4) and downregulated expression of the glutathione peroxidase 1 (Gpx1) gene as one of the most important antioxidant enzymes. MZB also induced apoptosis dose-dependently in the testes as determined by the terminal dUTP nick-end labeling assay and immunoblotting. NAC administration decreased the mRNA levels of both iNOS and NOX4 with a concomitant increase in Gpx1 expression. It also significantly decreased MZB-induced oxidative stress and apoptosis. Collectively, the present study showed MZB-induced oxidative damage in testes leading to apoptosis. It revealed that antioxidants such as NAC can mitigate oxidant injury induced by the dithiocarbamate pesticides in the reproductive system.

Mancozeb fungicide-induced genotoxic effects, metabolic alterations, and histological changes in the colon and liver of Sprague Dawley rats

“…On the other hand, serum total lipid content was significantly increased in female and male albino rats after being fed on diets containing chlorpyrifos (at 200 ppm), or chlorpyrifosmethyl (at 2000 ppm) for 12 weeks followed by a 3week recovery period (El-Tawil, 2014). It was also found that MNZ increased lipid peroxidation and protein carbonyl (Mohammadi et al, 2018). The increased cholesterol and LDL cholesterol levels could be attributed to hypothyroxinemia and inhibition of thyroid peroxidase that was induced by MNZ exposure as stated by Axelstad et al (2011).…”

“…On the other hand, serum total lipid content was significantly increased in female and male albino rats after being fed on diets containing chlorpyrifos (at 200 ppm), or chlorpyrifos-methyl (at 2000 ppm) for 12 weeks followed by a 3-week recovery period (El-Tawil, 2014). It was also found that MNZ increased lipid peroxidation and protein carbonyl (Mohammadi et al, 2018).…”

The effects of functionalization of carbon nanotubes on toxicological parameters in mice

“…Blood-testis barrier (BTB) was evaluated by the Evans blue extravasation method. 79,80 Evans blue (2% in saline, 3 mL/kg; Sigma-Aldrich) was given iv at 3 h before sacrificing followed by transcardial perfusion of NaCl 0.9% to remove the intravascular dye from the vessels until the drainage was colorless. Afterward, one testis was removed, weighed, dried in a desiccator oven for 48 h at 60 C, and reweighed.…”

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

“…Sperm parameters including motility, viability, and the number of sperms have been decreased by MZB (500 mg/kg) (Girish and Reddy, 2017). Another study in 2018 (Mohammadi-Sardoo et al, 2018) showed deleterious changes in the architecture of testis, oxidative stress imbalance, and apoptosis following MZB administration. It was also found to impair male fertility in rabbits with anti-spermatogenic and antisteroidogenic adverse effects (Elsharkawy et al, 2019).…”

“…Enhanced production of ROS is caused by infections, varicocele, cigarette smoking, ionizing radiation, psychological stress, spinal cord injury, and environmental pollution like pesticides (Bui et al, 2018). Reactive oxygen species generation, as second messenger, and induction of oxidative stress is a potential mechanism involved in reprotoxicity of MZB (Girish and Reddy, 2017;Liu et al, 2017;Mohammadi-Sardoo et al, 2018), which leads to the induction of cell death and infertility.…”