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4-Nitrophenol induces activation of Nrf2 antioxidant pathway and apoptosis of the germ cells in rat testes

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Abstract

The potential of 4-nitrophenol (PNP) to affect testicular function of rats was assessed by intratesticular injection (IT). The protective effects of phytosterin (PS) on PNP-induced injury were assessed. Rats were sacrificed on days 1, 3, and 7 after IT of PNP (0.1 M, 50 μl). PNP induced hemorrhage in intertubular areas and denudation of germinal epithelium. The expression of caspase-3 and sperm abnormalities were significantly increased (P < 0.05). The concentrations of testosterone in serum were significantly increased (P < 0.05) on the 1st and 3rd day. PNP induced oxidative stress in testes, which manifested increased SOD, CAT, GSH-Px activities, and increases in MDA, GSH, H2O2 concentrations (P < 0.05). The Nrf2 antioxidant pathway was activated as indicated by increased expression of Nrf2, HO-1, and GCLC mRNA (P < 0.05). Moreover, supplementation with PS resulted in an amelioration of PNP-induced oxidative damage. These results suggest that PNP induced activation of Nrf2 antioxidant pathway and apoptosis of the germ cells.

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Abbreviations

PNP:

4-Nitrophenol

ROS:

Reactive oxygen species

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

SOD:

Superoxide dismutase

CAT:

Catalase

Nrf2:

Nuclear factor erythroid 2-related factor 2

IT:

Intratesticular injection

PS:

Phytosterin

HO-1:

Heme oxygenase 1

GCLC:

γ-Glutamylcysteine synthetase

NQO1:

NAD(P)H: quinone oxidoreductase 1

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Acknowledgments

This work was supported by the National “Twelfth-Five Year” Research Program of China (2012BAD39B02), The National Natural Science Foundation of Jiangsu Province (BK20131315), Qing Lan Project, National Nature Science Foundation of China (No. 31272485), Scientific Research Foundation for Returned Scholars, Ministry of Education of China ([2012]940), and Graduate research and innovation projects of Jiangsu Province (CXLX13-29).

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Authors and Affiliations

  1. College of Animal Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China

    Yonghui Zhang, Yun Cao, Fei Wang, Meiyan Song, Xiaoli Rui, Yansen Li & ChunMei Li

  2. Laboratory of Nuclear Receptors and Cancer Research, Basic Medical Research Center, Nantong University School of Medicine, Nantong, 226001, Jiangsu, People’s Republic of China

    Yonghui Zhang

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  1. Yonghui Zhang
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  2. Yun Cao
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  4. Meiyan Song
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  7. ChunMei Li
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Correspondence to ChunMei Li.

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The experimental protocol was approved in accordance with the Guide for the Care and Use of Laboratory Animals prepared by the Institutional Animal Care and Use Committee, Nanjing Agricultural University.

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The authors declare that they have no conflict of interest.

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Zhang, Y., Cao, Y., Wang, F. et al. 4-Nitrophenol induces activation of Nrf2 antioxidant pathway and apoptosis of the germ cells in rat testes. Environ Sci Pollut Res 23, 13035–13046 (2016). https://doi.org/10.1007/s11356-016-6470-2

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