2. Academic Validation
  3. Oxidative stress and iron homeostasis imbalance mediate AlCl3-induced liver damage in mice

Oxidative stress and iron homeostasis imbalance mediate AlCl3-induced liver damage in mice

  • J Environ Sci (China). 2026 Feb:160:581-590. doi: 10.1016/j.jes.2025.04.055.
Hongfei Hu 1,  Guangji Wei 2,  Hai Lan 1,  Yang Feng 1,  Shihua Luo 3,  Yaqin Pang 4,  Yanxin Huang 3,  Huixiong Yuan 3,  Huixin Peng 5,  Wencheng Chen 6
Affiliations

Affiliations

  • 1 The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China.
  • 2 Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; Baise People's Hospital, Department of Laboratory, Baise, Guangxi 530000, China.
  • 3 The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China.
  • 4 Key Laboratory of Research on Environment and Population Health in aluminium mining areas (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, Guangxi 530000, China.
  • 5 The Second People's Hospital of Jinzhong, Department of Laboratory, Jinzhong, Shanxi 030800, China. Electronic address: [email protected].
  • 6 The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; National Immunological Laboratory of Traditional Chinese Medicine, Baise, Guangxi 533000, China; Key Laboratory of Research on Environment and Population Health in aluminium mining areas (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, Guangxi 530000, China. Electronic address: [email protected].
PMID: 41177639 DOI: 10.1016/j.jes.2025.04.055
Abstract

The liver, a critical metabolic organ, is particularly vulnerable to damage upon aluminum exposure. However, the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated. This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue. The results indicated that AlCl3 exposure induced significant liver dysfunction, characterized by reduced adenosine triphosphate levels, elevated plasma alanine aminotransferase and aspartate aminotransferase. Histopathological analysis of liver tissue revealed marked histological damage, accompanied by substantial iron deposition. Further examinations demonstrated elevated hepatic levels of malondialdehyde, 4-hydroxynonenal, and Reactive Oxygen Species, decreased levels of glutathione (GSH) and superoxide dismutase, increased levels of oxidized glutathione (GSSG), and a reduced GSH/GSSG ratio. The mRNA and protein expression of ferroptosis-related molecules, including downregulated Glutathione Peroxidase 4 and solute carrier family 7 member 11, were significantly downregulated, while acyl-CoA synthetase long-chain family member 4, ferritin heavy chain 1, and iron regulatory protein 1 levels were significantly upregulated. Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage, attenuating signs of Ferroptosis. These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.

Keywords

Aluminum; Ferroptosis; Iron deposition; Liver injury; Oxidative stress.

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