Dataset Information

Potential Role of Lycopene in the Inhibition of Di(2-ethylhexyl) Phthalate-Induced Ferroptosis in Spleen Via Modulation of Iron Ion Homeostasis.

ABSTRACT: 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.

SUBMITTER: Dai XY

PROVIDER: S-EPMC7887846 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Potential Role of Lycopene in the Inhibition of Di(2-ethylhexyl) Phthalate-Induced Ferroptosis in Spleen Via Modulation of Iron Ion Homeostasis.

Dai Xue-Yan XY Zhu Shi-Yong SY Li Mu-Zi MZ Talukder Milton M Zhao Yi Y Li Jin-Long JL

ACS pharmacology & translational science 20210127 1

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 ultrastructur ...[more]

PMID: 33615188

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Project description:Maintaining essential fatty acid (EFA) homeostasis during pregnancy is critical for fetal development. As the organ that controls the maternal-to-fetal supply of nutrients, the placenta plays a significant role in guiding EFA transfer to the fetus. Many EFA homeostasis proteins are regulated by peroxisome proliferator-activated receptors (PPARs). The metabolites of di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous environmental contaminant, might influence EFA homeostasis via trans-activation of PPARs with subsequent downstream effects on EFA transporters and enzymes. To investigate DEHP's effect on placental/fetal EFA homeostasis, female Sprague-Dawley rats were orally gavaged with either vehicle or DEHP at 750 or 1500 mg/kg/day from gestational day (GD) 0 to GD 19. Changes in the expression of several EFA homeostasis regulating proteins were determined in the junctional (JXN) and labyrinthine (LAB) zones of the placenta, including PPAR isoforms (alpha, beta and gamma), fatty acid translocase (FAT/CD36), fatty acid transport protein 1 (FATP1), plasma membrane fatty acid binding protein (FABPpm), heart cytoplasmic fatty acid binding protein (HFABP), cytochrome P450 (CYP) 4A1, and cyclooxygenase (COX)-1 and -2. Additionally, effects of DEHP maternal exposure on the placental transfer and fetal distribution of representative EFAs, arachidonic acid (AA) and docosahexaenoic acid (DHA), and the placental production of prostaglandins (PGs) were investigated. Expression of PPARalpha, PPARgamma, FAT/CD36, FATP1, HFABP and CYP4A1 was up-regulated in JXN and/or LAB while COX-2 was down-regulated in JXN. PPARbeta, FABPpm, and COX-1 demonstrated variable expression. Reduced directional maternal-to-fetal placental transfer and altered fetal distribution of AA and DHA were observed in concordance with a decreased total placental PG production. These results correlate with previous in vitro data, suggesting that DEHP could influence placental EFA homeostasis with potential downstream effects in the developing fetus.

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Dataset Information

Potential Role of Lycopene in the Inhibition of Di(2-ethylhexyl) Phthalate-Induced Ferroptosis in Spleen Via Modulation of Iron Ion Homeostasis.

Publications

Potential Role of Lycopene in the Inhibition of Di(2-ethylhexyl) Phthalate-Induced Ferroptosis in Spleen Via Modulation of Iron Ion Homeostasis.

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