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Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd

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Abstract

Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3 exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3 exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3 exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl3 exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3 exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl3 exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3 exposure and offer a foundation for future research in this area.

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Funding

We thank the Guangxi Natural Science Foundation Project (2020GXNSFAA297257), National Natural Science Foundation of China (81960303), Guangxi University Young and Middle-aged Teachers' Basic Ability Improvement Project (2020KY13017), Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Self-financing Scientific Research Project (GZZC2020248), and Guangxi Zhuang Autonomous Region Health and Health Commission Self-financing Scientific Research Course (Z20201416).

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  1. The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China

    Hui- xin Peng, Fu Chai, Ke-heng Chen, Yan-xin Huang, Guang-ji Wei, Huixiong Yuan, Yan-fang Pang, Shi-hua Luo, Chun-fang Wang & Wen-cheng Chen

  2. Graduate School of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China

    Hui- xin Peng, Fu Chai, Ke-heng Chen, Yan-xin Huang, Guang-ji Wei, Huixiong Yuan, Yan-fang Pang, Shi-hua Luo, Chun-fang Wang & Wen-cheng Chen

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Hui-xin Peng, fu Chai and Ke-heng Chen were responsible for experiment operation and paper writing; Yan-xin Huang, Yan-fang Pang and Hui-xiong Yuan were responsible for animal feeding and modeling; Guang-ji Wei was responsible for partial data analysis; Wen-cheng Chen, Chun-fang Wang and Shi-hua Luo were responsible for experiment design, paper writing guidance, overall framework construction and project fund preparation.

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Correspondence to Shi-hua Luo, Chun-fang Wang or Wen-cheng Chen.

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Peng, H.x., Chai, F., Chen, Kh. et al. Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd. Biol Trace Elem Res 202, 2616–2629 (2024). https://doi.org/10.1007/s12011-023-03848-0

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