Di-2-ethylhexyl phthalate (DEHP) induced lipid metabolism disorder in liver via activating the LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathway

Huang, Yue-Qiang; Tang, Yi-Xi; Qiu, Bai-Hao; Talukder, Milton; Li, Xue-Nan; Li, Jinlong

doi:10.1016/j.fct.2022.113119

Cited by 71 publications

(28 citation statements)

References 84 publications

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“…29 When IL-6, IL-10 or other cytokines promote STAT3 phosphorylation, Foxo1 will be released to play its function role. 29,44–46 It was found that the level of IL-6 was increased in ATZ treated groups (Fig. 1E).…”

Section: Discussionmentioning

confidence: 82%

IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

Zhu

Tong

et al. 2022

Food Funct.

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Section: Discussionmentioning

confidence: 82%

IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

Zhu

Tong

et al. 2022

Food Funct.

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“…Di-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers in daily life . DEHP is not covalently combined with plastic products; it is continuously released from plastic products and directly penetrates food, water, and air, which can pose a public health threat via dermal absorption, inhalation, and the food chain. , Hence, DEHP has attracted much attention due to its potentially harmful effects. In recent years, studies determined the toxic effects of DEHP in a variety of tissues, such as the liver, kidney, and lungs. − DEHP exposure could cause abnormal expression and dysfunction of the inflammatory response .…”

Section: Introductionmentioning

confidence: 99%

Role of Toll-like Receptor/MyD88 Signaling in Lycopene Alleviated Di-2-ethylhexyl Phthalate (DEHP)-Induced Inflammatory Response

Dai

Zhu²,

Chen³

et al. 2022

J. Agric. Food Chem.

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Lycopene (Lyc) has anti-inflammatory and antioxidant biological functions. Di-2-ethylhexyl phthalate (DEHP) is an extremely harmful and persistent environmental pollutant and is a threat to animal health. The toll-like receptor (TLR)/MyD88 pathway is an important pathway in the inflammatory response. To illustrate the potential antagonistic action of Lyc against DEHP by the TLR/MyD88 pathway, 140 ICR mice were randomly assigned groups and continuously gavaged with corn oil, distilled water, different DEHP concentrations (500 or 1000 mg/kg BW/day), and/or Lyc (5 mg/kg BW/day) for 28 days. The data show that Lyc effectively attenuates the DEHP-induced activation of the TLR/MyD88 pathway, the upregulation of JNK expression, the content of IL-6 and TNF-α, and the downregulation of the IL-10 content, which eventually inhibit the inflammatory response and mitochondrial injuries. These findings underline the TLR/MyD88 pathway as a potential therapeutic target in DEHP and Lyc as a new therapeutic method to inhibit DEHP toxicity.

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“…Huang et al concluded that DEHP induced lipid metabolism disorder in the liver by activating the LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathways. Lo et al found that DEHP induced injury in liver FL83B cells ( Lo et al, 2014 ; Chen et al, 2016 ; Huang et al, 2022 ). Consistent with previous studies, we discovered elevated ALT and AST and hepatocyte morphology changes after gestational DEHP exposure in pregnant mice.…”

Section: Discussionmentioning

confidence: 99%

Di-(2-ethylhexyl) phthalate exposure induces liver injury by promoting ferroptosis via downregulation of GPX4 in pregnant mice

Zhang

Zhen

Cheng

et al. 2022

Front. Cell Dev. Biol.

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As one kind of endocrine disrupting chemical, di-(2-ethylhexyl) phthalate (DEHP) has been reported to cause liver dysfunction in epidemiological and experimental studies. Abnormal liver function in pregnancy is associated with adverse maternal and perinatal outcomes. Few studies have investigated the potential effect of gestational DEHP exposure on the liver in pregnant mice, and the underlying mechanisms remain unclear. In the present study, pregnant ICR mice were exposed to doses (0, 500, 1,000 mg/kg/day) of DEHP in the presence or absence of 5 mg/kg/day ferrostatin-1 (Fer-1, ferroptosis inhibitor) by oral gavage from gestation day 4 to day 18. HepG2 cells were exposed to different doses of monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) in vitro. Hepatic function and pathologic changes were observed. Oxidative stress, iron metabolism, and ferroptosis-related indicators and genes were evaluated both in vivo and in vitro. The results showed that gestational DEHP exposure induced disordered liver function and hepatocyte morphology changes in pregnant mice, along with increased malondialdehyde (MDA) and Fe2+ content and decreased glutathione (GSH) levels. The expression levels of the selected ferroptosis-related genes Slc7a11, Gpx4, and Nfr2 were significantly decreased, and Ptgs2 and Lpcat3 were significantly increased. Notably, Fer-1 attenuated DEHP-induced liver injury and ferroptosis. Furthermore, MEHP exhibited a synergistic effect with RSL3 (a GPX4 inhibitor) in promoting ferroptosis in vitro. Taken together, the results demonstrated that DEHP induced liver injury and ferroptosis in pregnant mice, probably by inhibiting the GPX4 pathway through lipid peroxidation and iron accumulation.

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Di-2-ethylhexyl phthalate (DEHP) induced lipid metabolism disorder in liver via activating the LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathway

Cited by 71 publications

References 84 publications

IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

Role of Toll-like Receptor/MyD88 Signaling in Lycopene Alleviated Di-2-ethylhexyl Phthalate (DEHP)-Induced Inflammatory Response

Di-(2-ethylhexyl) phthalate exposure induces liver injury by promoting ferroptosis via downregulation of GPX4 in pregnant mice

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