Protective effects of vitamin E against reproductive toxicity induced by di(2-ethylhexyl) phthalate via PPAR-dependent mechanisms

Wang, Yangcai; Chen, Bailin; Lin, Tao; Wu, Shengde; Wei, Guanghui

doi:10.1080/15376516.2017.1333556

Cited by 29 publications

(18 citation statements)

References 46 publications

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“…People are inevitably exposed to phthalates through environmental contamination. Exposure to DEHP was associated with a variety of toxicological outcomes in mammals such as reproductive toxicity (Wang et al 2017), neurotoxicity (You et al 2018), carcinogenicity (Chen et al 2017), hepatotoxicity (Zhang et al 2018), and lipid metabolism disruption (Pradhan et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Di(2-ethylhexyl) phthalate inhibits glutathione regeneration and dehydrogenases of the pentose phosphate pathway on human colon carcinoma cells

Amara

Timoumi

Annabi

et al. 2020

Cell Stress and Chaperones

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Phthalates, particularly di(2-ethylhexyl) phthalate (DEHP), are compounds widely used as plasticizers and have become serious global contaminants. Because of the bioaccumulation of such substances, the food chain is at risk. The food contamination by some phthalates has been linked to different side effects in experimental animals. That is why we have chosen the intestinal system's cells which represent the primary targets of these compounds to test their toxic effects. Human colon carcinoma cells (HCT 116) were chosen to elucidate whether DEHP triggers oxidative stress and apoptosis. Our results indicated that DEHP is cytotoxic; it induces the overexpression of Hsp70 protein and causes oxidative damage through the generation of free radicals leading to lipid peroxidation induction and the increase of superoxide dismutase (SOD) and catalase (CAT) activities. In addition, cell treatment with DEHP resulted in a glutathione (GSH) content decrease and a decrease in the glutathione reductase (GR) activity. As new evidence provided in this study, we demonstrated that the DEHP affected the two enzymes' activities of the oxidative phase of the pentose phosphate pathway: Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). This leads to a decrease in the level of NADPH used by the GR to maintain the regeneration of the reduced GSH. We also demonstrated that such effects can be responsible for DEHP-induced apoptosis.

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Section: Discussionmentioning

confidence: 99%

Di(2-ethylhexyl) phthalate inhibits glutathione regeneration and dehydrogenases of the pentose phosphate pathway on human colon carcinoma cells

Amara

Timoumi

Annabi

et al. 2020

Cell Stress and Chaperones

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“…People are inevitably exposed to phthalate through environmental contamination. Exposure to DEHP was associated with a variety of toxicological outcomes in mammals, reproductive toxicity, 39 neurotoxicity, 40 carcinogenicity, 41 hepatotoxicity, 42 and lipid metabolism disruption. 43 In this study, we focused on the harmful effect of this plasticizer on HEK-293 cell line, given that the kidney is one of DEHP target organ.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Amara

Timoumi

Graiet

et al. 2019

Environmental Toxicology

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The di (2‐ethylhexyl) phthalate (DEHP) is a plasticizer used in the polyvinyl chloride industry. Human exposure to this plasticizer is inevitable and contributes to several side effects. In this study, we examined whether DEHP induces apoptosis and oxidative stress in embryonic kidney cells (HEK‐293) and whether the nuclear factor E2‐related factor 2 (Nrf‐2)/heme oxygenase‐1 (HO‐1) antioxidant pathway is involved in the pathogenesis of this process. We demonstrated that DEHP is cytotoxic to HEK‐293 cells. It causes oxidative damage through the generation of free radicals, induces lipid peroxidation, and alters superoxide dismutase and catalase activities. Simultaneously, DEHP treatment decreases the expression and the protein level of Nrf‐2 and HO‐1. Inhibition of the Nrf‐2/HO‐1 pathway is related to the mitochondrial pathway of apoptosis. This apoptotic process is characterized by a loss of mitochondrial transmembrane potential (ΔΨm) and upregulation of the expression of caspase‐3 mRNA as well as its protein level.

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“…For instance, DEHP impairs the reproduction in zebrafish by inducing a mitotic arrest during spermatogenesis, increasing DNA fragmentation in sperm cells and markedly reducing embryo production (Corradetti et al, 2013). DEHP can also induce testicular toxicity in male rats, causing the change of testicular weight and histology and leading to apoptosis and reproductive malformations, explained by peroxisome proliferator-activated receptor-dependent mechanisms (Wang et al, 2017). Additionally, DEHP exposure in utero can damage Sertoli cells in the postnatal life of mice offspring via disturbing sex differentiation pathways, potentially inducing decreases in spermatogenesis (Wang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Di(2-ethylhexyl)phthalate induces reproductive toxicity via JAZF1/TR4 pathway and oxidative stress in pubertal male rats

Shi

Zhao

et al. 2019

Toxicol Ind Health

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Di(2-ethylhexyl)phthalate (DEHP) is a typical endocrine-disrupting chemical and reproductive toxicant. Although previous studies have attempted to describe the mechanism by which DEHP exposure results in reproductive dysfunction, few studies focused on puberty, a critical period of reproductive development, and the increased susceptibility to injury in adolescents. To elucidate the mechanism underpinning the testicular effects of DEHP in puberty, we sought to investigate the JAZF1/TR4 pathway in the testes of pubertal rats. Specifically, we focused on the role of the JAZF1/TR4 pathway in male reproduction, including the genes JAZF1, TR4, Sperm 1, and Cyclin A1. In the present study, rats were exposed to increasing concentrations of DEHP (0, 250, 500, and 1000 mg/kg/day) by oral gavages for 30 days. Then we assayed testicular zinc and oxidative stress levels. Our results indicated that DEHP exposure could lead to oxidative stress and decrease the contents of testicular zinc. Additionally, significant morphological changes and cell apoptosis were observed in testes exposed to DEHP, as identified by hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase-mediated nick and labeling assay. By measuring the expression levels of the above relevant genes by qPCR, we found the DEHP-induced increased expression of JAZF1 and decreased expression of TR4, Sperm 1, and Cyclin A1. Therefore, we have demonstrated that in vivo exposure to DEHP might induce reproductive toxicity in pubertal male rats through the JAZF1/TR4 pathway and oxidative stress.

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Protective effects of vitamin E against reproductive toxicity induced by di(2-ethylhexyl) phthalate via PPAR-dependent mechanisms

Abstract: Vitamin E cotreatment showed protective effects against DEHP-induced testicular toxicity, including reproductive malformations, testicular weight, apoptosis and histology, and the mechanisms maybe associated with PPARs.

Cited by 29 publications

References 46 publications

Di(2-ethylhexyl) phthalate inhibits glutathione regeneration and dehydrogenases of the pentose phosphate pathway on human colon carcinoma cells

Di(2-ethylhexyl) phthalate inhibits glutathione regeneration and dehydrogenases of the pentose phosphate pathway on human colon carcinoma cells

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Di(2-ethylhexyl)phthalate induces reproductive toxicity via JAZF1/TR4 pathway and oxidative stress in pubertal male rats

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