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

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.