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Zinc Inhibits Lead-Induced Oxidative Stress and Apoptosis of ST Cells Through ROS/PTEN/PI3K/AKT Axis

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Abstract

Lead (Pb) is a widely distributed toxic heavy metal element known to have strong male reproductive toxicity, which can result in issues such as abnormal count and morphology of sperm. Zinc (Zn) is an essential trace element for the human body that can antagonize the activity of Pb in some physiological environments, and it also possesses antioxidant and anti-inflammatory effects. However, the specific mechanism of Zn’s antagonism against Pb remains largely unclear. In our study, we conducted research using swine testis cells (ST cells) and confirmed that the half maximal inhibitory concentration of Pb on ST cells was 994.4 μM, and the optimal antagonistic concentration of Zn was 10 μM. Based on this information, we treated ST cells with Pb and Zn and detected related indices such as apoptosis, oxidative stress, and the PTEN/PI3K/AKT pathway using flow cytometry, DCFH-DA staining, RT-PCR, and Western blot. Our results demonstrated that Pb exposure can generate excessive reactive oxygen species (ROS), disrupt the antioxidant system, upregulate PTEN expression, and inhibit the PI3K/AKT pathway in ST cells. In contrast, Zn significantly inhibited the overproduction of ROS, improved oxidative stress, and decreased PTEN expression, thus protecting the PI3K/AKT pathway compared to Pb-exposed ST cells. Furthermore, we found that Pb exposure exacerbated the expression of genes related to the apoptosis pathway and reduced the expression of anti-apoptotic genes. Furthermore, this situation was significantly improved when co-cultured with Pb and Zn. In summary, our study demonstrated that Zn alleviated Pb-induced oxidative stress and apoptosis through the ROS/PTEN/PI3K/AKT axis in ST cells.

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Authors and Affiliations

  1. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People’s Republic of China

    Haoyu Zhang, Kexin Sun, Meichen Gao & Shiwen Xu

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  1. Haoyu Zhang
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  2. Kexin Sun
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Contributions

Haoyu Zhang was in charge of conceptualization, methodology, formal analysis, data curation, and writing the main manuscript text.

Kexin Sun was in charge of resources, visualization, and also writing part of the manuscript text.

Meichen Gao was in charge of validation and investigation.

Shiwen Xu was in charge of review and editing the manuscript text.

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Correspondence to Shiwen Xu.

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Zhang, H., Sun, K., Gao, M. et al. Zinc Inhibits Lead-Induced Oxidative Stress and Apoptosis of ST Cells Through ROS/PTEN/PI3K/AKT Axis. Biol Trace Elem Res 202, 980–989 (2024). https://doi.org/10.1007/s12011-023-03721-0

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