Supplemental dietary phytosterin protects against 4-nitrophenol-induced oxidative stress and apoptosis in rat testes

Abstract

4-Nitrophenol (PNP), is generally regarded as an environmental endocrine disruptor (EED). Phytosterin (PS), a new feed additive, possesses highly efficient antioxidant activities. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2), is an important regulator of cellular oxidative stress. Using rats, this study examined PNP-induced testicular oxidative damage and PS-mediated protection against that damage. The generation of MDA and H2O2 upon PNP and PS treatment was milder than that upon treatment with PNP alone. This mitigation was accompanied by partially reversed changes in SOD, CAT, GSH and GSH-Px. Moreover, PNP significantly reduced the caudal epididymal sperm counts and serum testosterone levels. Typical morphological changes were also observed in the testes of PNP-treated animals. PNP reduced the transcriptional level of Nrf2, as evaluated by RT-PCR, but it promoted the dissociation from the Nrf2 complex, stabilization and translocation into the nucleus, as evaluated by immunohistochemistry and Western blotting. In addition, PNP enhanced the Nrf2-dependent gene expression of heme oxygenase-1 (HO-1) and glutamate–cysteine ligase catalytic subunit (GCLC). These results suggest that the Nrf2 pathway plays an important role in PNP-induced oxidative damage and that PS possesses modulatory effects on PNP-induced oxidative damage in rat testes.

Potential protective effect of arginine against 4-nitrophenol-induced ovarian damage in rats

“…Zhang et al (2015) demonstrated that phytosterin has a protective role in PNP-induced reproductive toxicity and apoptosis in germ cells of rats.…”

“…Nevertheless, studies on PNP-induced female reproductive toxicity in rats are lacking and the underlying mechanism by which it does so has not been explained thoroughly. In a previous study, it was suggested that increased production of free oxygen radicals and decreased production of antioxidants could have an impact on the occurrence of PNP toxicity (Zhang et al, 2015). It has been claimed that organ damage related to free radicals occurs as a consequence of disrupted antioxidant defense mechanisms.…”

Oxidative stress-induced alterations in seminal plasma antioxidants: Is there any association with keap1 gene methylation in human spermatozoa?

“…It is well documented that the Keap1 ‐Nrf2 pathway is one of the chief regulators of cellular defence against ROS in sperm cells (Hanada et al, ; Schmidt, Hangmann, Shams, Avivi, & Hankeln, ; Zhang, Liu, et al, ; Zhang, Song, et al, ). Nrf2 mRNA expression is also reported to have significance in spermatogenesis and sperm‐specific functions like motility (Chen et al, ).…”

“…Keap1 ‐Nrf2 signalling pathway has been shown to be impaired in some OS‐associated diseases, caused by mutations within the Keap1‐Nrf2 gene, hypermethylation of the keap1 promoter region or resistance of the transcription factor Nrf2 to OS by binding to ARE in the promoters of antioxidant and detoxifying genes (Barbano et al, ; Chen, Mai, Zhou, Gao, & Yu, ; Copple, ; Copple et al, ; Hanada et al, ; Liu et al, ; Zipper, & Mulcahy, ). Nrf2 mRNA expression has also been suggested to be essential for normal spermatogenesis and sperm‐specific function like motility and can be decreased with ROS elevation in spermatozoa (Chen et al, ; Hagan et al, ; Hanada et al, ; Yu, & Huang, ; Zhang, Liu, et al, ; Zhang, Song, et al, ). Moreover, in different human cell types, it was demonstrated that hypermethylation of keap1 gene impairs the keap1 ‐Nrf2 signalling pathway (Guo et al, ; Hanada et al, ; Wang et al, ).…”

4‐nitrophenol exposure in T24 human bladder cancer cells promotes proliferation, motilities, and epithelial‐to‐mesenchymal transition

“…As an environmental endocrine disruptor (Hass et al ), PNP has shown estrogenic and antiandrogenic activities (Taneda et al ; Li et al ). Previous studies indicated that PNP had potential adverse effects, such as disturbing the endocrine and reproductive systems (Mi et al , ; Zhang et al , , ; Ahmed et al ). We demonstrated that PNP induces autophagy in human normal prostate epithelial cells and the activation of autophagy plays a protective role in cellular oxidative stress and apoptosis (Zhang et al ).…”