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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Predictive Toxicology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1499116
This article is part of the Research Topic Toxicity Mechanisms, Exposure, Toxicokinetic and Risk Assessment Aspects of Metals, Toxic for Animals and Humans, Volume III View all 4 articles

Monocrotaline-mediated autophagy via inhibiting PI3K/AKT/mTOR pathway induces apoptosis in rat hepatocytes

Provisionally accepted
Yazhou Guo Yazhou Guo 1Yang Yuan Yang Yuan 1*Ruibo Wang Ruibo Wang 1*Jun Bai Jun Bai 1*Yanqing Jia Yanqing Jia 1*Xinxin Qiu Xinxin Qiu 1*Huafeng Niu Huafeng Niu 1*Long Li Long Li 1*Yan Luo Yan Luo 1*Baoyu Zhao Baoyu Zhao 2*Zhencang Zhang Zhencang Zhang 1*
  • 1 Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
  • 2 College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, China

The final, formatted version of the article will be published soon.

    Monocrotaline (MCT), a major pyrrolizidine alkaloid, is well-known for its high liver toxicity. Dysregulation of autophagy induced apoptosis can lead to various liver diseases, including those induced by chemical compounds. Therefore, we aim to explore whether autophagy might serve as a potential strategy for addressing liver apoptosis caused by MCT. In primary rat hepatocytes (PRHs), MCT significantly increased the number of autophagosomes and the expression levels of LC3II, Becline-1, and Atg5, while it decreased the expression of p62 in a concentration-dependent manner at doses of 100, 200, 300, and 400 μM. Western blot assays revealed MCT inhibited the phosphorylation levels of the PI3K/AKT/mTOR pathway. To elucidate the role of autophagy in mediating MCT-induced apoptosis, we further pretreated PRHs with the autophagy agonist Rapamycin and the inhibitors Bafilomycin A1 and Chloroquine, respectively, and assessed the apoptosis of PRHs induced by MCT. The results displayed that Rapamycin increased the apoptosis rate and the expression of cleaved caspase-3, whereas Bafilomycin A1 and Chloroquine reduced the apoptosis and the expression of cleaved caspase-3 in PRHs. This study 删除了: Bafilomycin 30 删除了: Bafilomycin 31 2 confirms that autophagy enhances PRHs apoptosis induced by MCT. In summary, this study demonstrates that MCT-induced autophagy via inhibition of the PI3K/AKT/mTOR pathway can lead to apoptosis in PRHs.

    Keywords: Monocrotaline, Hepatotoxicity, Autophagy, PI3K/Akt/mTOR signaling pathway, Apoptosis

    Received: 20 Sep 2024; Accepted: 11 Oct 2024.

    Copyright: © 2024 Guo, Yuan, Wang, Bai, Jia, Qiu, Niu, Li, Luo, Zhao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yang Yuan, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Ruibo Wang, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Jun Bai, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Yanqing Jia, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Xinxin Qiu, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Huafeng Niu, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Long Li, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Yan Luo, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China
    Baoyu Zhao, College of Veterinary Medicine, Northwest A&F University, Xianyang, 712100, Shaanxi, China
    Zhencang Zhang, Yangling Vocational & Technical College, Yangling, Shaanxi Province, China

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