MIOX Aggravated DEHP-Induced Ferroptosis in Chicken Hepatocytes by Targeting STAT3 Phosphorylation

  • J Agric Food Chem. 2025 Oct 22;73(42):27025-27037. doi: 10.1021/acs.jafc.5c10368.
Ning-Ning Huang  1 ,  Ping-An Jian  1 ,  Jia-Yu Du  1 ,  Wen-Na Cai  1 ,  Tian-Ning Yang  1 ,  Zhi-Juan Wang  1 ,  Shi-Yong Zhu  1 ,  Kai Guo  2 ,  Jin-Long Li  1  3  4 ,  Chi-Chiu Wang  5 ,  Xue-Nan Li  1  3  4  5
Affiliations
  • 1. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • 2. Chifeng Agriculture and Animal Husbandry Comprehensive Administrative Law Enforcement Detachment, Chifeng City, Inner Mongolia 024000, China.
  • 3. Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • 4. Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • 5. Department of Obstetrics & Gynaecology, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, and The Chinese University of Hong Kong-Sichuan University Joint Laboratory for Reproductive MedicineThe Chinese University of Hong Kong, Hong Kong, China.
PMID: 41070917 DOI: 10.1021/acs.jafc.5c10368
Abstract

Global health issues have been heightened by di-(2-ethylhexyl) phthalate (DEHP), a commonly utilized plasticizer, due to its liver toxicity and potential to cause liver damage. Ferroptosis, a type of nonapoptotic cell death reliant on iron, is associated with multiple liver disorders. This research aimed to explore the role and mechanisms of Ferroptosis in DEHP-induced liver toxicity in chickens. In vivo experiments showed that DEHP exposure caused liver damage. Transcriptomic analysis revealed that DEHP exposure activated Ferroptosis and significantly upregulated myo-inositol oxygenase (MIOX) expression. Subsequent in vitro experiments using LMH cells revealed that reducing MIOX levels diminished Ferroptosis caused by mono- (2-ethylhexyl) phthalate (MEHP), DEHP's main metabolite, through the stimulation of the STAT3 signaling pathway. Our findings highlight the important role of MIOX in DEHP-induced liver injury via STAT3 signaling pathway. This study provides new evidence that MIOX is a potential therapeutic target for iron toxicosis associated liver diseases.

Keywords
MIOX; STAT3; di-(2-ethylhexyl) phthalate; ferroptosis; hepatocytes.
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