期刊
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
卷 4, 期 1, 页码 386-395出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsptsci.1c00001
关键词
di(2-ethylhexyl) phthalate; lycopene; ferroptosis; iron ion homeostasis; spleen
资金
- National Natural Science Foundation of China [31572586]
- Excellent Youth Foundation of Heilongjiang Province of China [JC2017005]
- China Agriculture Research System [CARS-35]
This study suggests that exposure to DEHP can trigger splenic cell death through ferroptosis, while supplementation of Lycopene can effectively inhibit these changes, providing new evidence for intervention and prevention of DEHP-related diseases.
Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical and widely used as a plasticizer. Humans can be exposed to DEHP through direct contact or environmental contamination. Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. 140 male mice were assigned into control, vehicle control, Lyc (5 mg/kg BW/d), DEHP (500 and 1000 mg/kg BW/d, respectively), and DEHP + Lyc groups and treated with an oral gavage that lasted 28 d. The ultrastructural results showed that DEHP induced pathological changes and mitochondrial injuries. We further revealed that DEHP exposure destroyed the Fe2+ imbalance homeostasis and, consequently, increases of lipid peroxidation and inhibition of cysteine/glutamate antiporter, all of which were involved in the process of ferroptsis. Moreover, the supplementation of Lyc significantly inhibited the ferroptsis changes mentioned above. Altogether, these results indicated that DEHP exposure triggered splenic cell death via ferroptosis; meanwhile, they also shed new evidence on a potential clue for the intervention and prevention of DEHP-related diseases.
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