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Activated Nrf-2 Pathway by Vitamin E to Attenuate Testicular Injuries of Rats with Sub-chronic Cadmium Exposure

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Abstract

Cadmium (Cd), a heavy metal element, cumulates in the testis and can cause male reproductive toxicity. Although vitamin E (VE) as one of potential antioxidants protects the testis against toxicity of Cd, the underlying mechanism remained uncompleted clear. The aim of this study was to investigate whether the Nrf-2 pathway is involved with the protective effect of VE on testicular damages caused by sub-chronic Cd exposure. Thirty-two SD rats were divided into four groups and orally administrated with VE and/or Cd for 28 consecutive days: control group, VE group (100 mg VE/kg), Cd group (5 mg CdCl2/kg), and VE + Cd group (100 mg VE/kg + 5 mg CdCl2/kg). The results showed that 28-day exposure of Cd caused accumulation of Cd, histopathological lesions, and alternations of sperm parameters (elevated rate of abnormal sperm, decreased count of sperm, declined motility, and viability of sperm). Moreover, the rats exposed to Cd showed significant oxidative stress (increased contents of MDA and decreased levels or activities of T-AOC, GSH, CAT, SOD and GSH-Px) and inhibition of Nrf-2 signaling pathway (downregulation of Nrf-2, HO-1, NQO-1, GCLC, GCLM and GST) of the testes. In contrast, VE treatment significantly reduced the Cd accumulation, alleviated histopathological lesions and dysfunctions, activated Nrf-2 pathway, and attenuated the oxidative stress caused by Cd in the testes of rats. In conclusion, VE, through upregulating Nrf-2 pathway, could protect testis against oxidative damages induced by sub-chronic Cd exposure.

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All data used to support the findings of this study are included within the article.

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Funding

This work was supported by National key research and development project (2018YFD0501800), Sichuan Science and Technology Program (2018NZ0002, 2019YFQ0012), and Sichuan beef cattle innovation team of National modern agricultural industry technology system (SCCXTD-2020–13).

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  1. Zhuo Chen, Zhicai Zuo, Kejie Chen, Zhuangzhi Yang, Fengyuan Wang contributed equally to this work

Authors and Affiliations

  1. College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China

    Zhuo Chen, Zhicai Zuo, Jing Fang, Hengmin Cui, Hongrui Guo, Ping Ouyang, Zhengli Chen, Chao Huang, Yi Geng, Wentao Liu & Huidan Deng

  2. School of Public Health, Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China

    Kejie Chen

  3. Chengdu Academy of Agriculture and Forestry Sciences, Chengdu, Sichuan, 611130, People’s Republic of China

    Zhuangzhi Yang

  4. College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu, Sichuan, 610041, People’s Republic of China

    Fengyuan Wang

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Contributions

Zhuo Chen, Zhicai Zuo, Kejie Chen, Zhuangzhi Yang, Fengyuan Wang, and Jing Fang designed and performed experiments, collected and analyzed data, and wrote the paper. Hengmin Cui, Hongrui Guo, Ping Ouyang, Zhengli Chen, Chao Huang, Yi Geng, Wentao Liu, and Huidan Deng performed experiments. All authors contributed discussions and interpretations.

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Correspondence to Jing Fang.

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Chen, Z., Zuo, Z., Chen, K. et al. Activated Nrf-2 Pathway by Vitamin E to Attenuate Testicular Injuries of Rats with Sub-chronic Cadmium Exposure. Biol Trace Elem Res 200, 1722–1735 (2022). https://doi.org/10.1007/s12011-021-02784-1

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