1. Academic Validation
  2. Chronic arsenic exposure induces ferroptosis via enhancing ferritinophagy in chicken livers

Chronic arsenic exposure induces ferroptosis via enhancing ferritinophagy in chicken livers

  • Sci Total Environ. 2023 May 16;164172. doi: 10.1016/j.scitotenv.2023.164172.
Lu Yu 1 Zhanjun Lv 1 Siyu Li 1 Huijie Jiang 1 Biqi Han 1 Xiaoyan Zheng 1 Yunfeng Liu 1 Zhigang Zhang 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin 150030, China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin 150030, China. Electronic address: zhangzhigang@neau.edu.cn.
Abstract

Arsenic (As) is a well-known pollutant in the environment, whose contamination in groundwater is a serious threat to Animals and humans. Ferroptosis, a form of cell death caused by iron-dependent lipid peroxidation, is involved in various pathological processes. Ferritinophagy is the selective Autophagy of ferritin and a crucial step in the induction of Ferroptosis. However, the mechanism of ferritinophagy in poultry livers exposed to As has not been studied yet. In this study, we investigated whether As-induced chicken liver injury is related to ferritinophagy-mediated Ferroptosis at the cellular and animal levels. Our results found that As exposure activated the AMPK/mTOR/ULK1 signaling pathway and significantly changed the protein levels of Ferroptosis and autophagy-related proteins in chicken livers. Moreover, As induced iron overload and lipid peroxidation in vitro. Interestingly, pretreatment with ferrostatin-1, chloroquine, and deferiprone alleviated these aberrant effects. Using chloroquine, we found that As-induced Ferroptosis is autophagy-dependent. Our findings further suggest that ferritinophagy is involved in chicken liver injury by showing that chronic As exposure increased mRNA expression of NCOA4 and decreased mRNA expression of FTH1. In conclusion, ferritinophagy-mediated Ferroptosis is one of the critical mechanisms of As-induced chicken liver injury. Inhibiting Ferroptosis may provide new insights for preventing and treating liver toxicity induced by environmental As exposure in livestock and poultry.

Keywords

Arsenic; Autophagy; Ferritinophagy; Ferroptosis; Iron overload.

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