Effects of di(2-ethylhexyl)phthalate exposure on 1,2-dimethyhydrazine-induced colon tumor promotion in rats

Chen, Hsin-Pao; Pan, Min‐Hsiung; Chou, Yuan-Yi; Sung, Chieh; Lee, Kuo-Hsin; Leung, Chung-Man; Hsu, Ping-Chi

doi:10.1016/j.fct.2017.03.014

Cited by 27 publications

(19 citation statements)

References 44 publications

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“…Intestinal oxidative stress is recognized as a major contributor to intestinal injury, resulting in endotoxin translocation (Assimakopoulos et al, 2004). Previous study reported that DEHP exposure induces colon tumor promotion in rats (Chen et al, 2017). The pulmonary inflammation in rat offspring were exacerbated when pregnant or lactating rats were exposed to DEHP with the increased inflammatory factor IL-4 (Wang et al, 2018).…”

Section: Discussionmentioning

confidence: 95%

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

Tian

Feng

et al. 2019

Front. Cell. Infect. Microbiol.

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Diethylhexylphthalate (DEHP), acting as an endocrine disruptor, disturbed reproductive health. Here, we evaluated the effects of Lactobacillus plantarum TW1-1 ( L. plantarum TW1-1) on DEHP-induced testicular damage in adult male mice. Results showed that oral supplementation of L. plantarum TW1-1 significantly increased the serum testosterone concentration, enhanced the semen quality, and attenuated gonad development defects in DEHP-exposed mice. L. plantarum TW1-1 also alleviated DEHP-induced oxidative stress and inflammatory responses by decreasing the mRNA expression and serum protein concentration of different inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1β and IL-6]. Furthermore, L. plantarum TW1-1 significantly reduced DEHP-induced intestinal hyper-permeability and the increase in the serum lipopolysaccharide level. Gut microbiota diversity analysis revealed that L. plantarum TW1-1 shifted the DEHP-disrupted gut microbiota to that of the control mice. At phylum level, L. plantarum TW1-1 reversed DEHP-induced Bacteroidetes increase and Firmicutes decrease, and restored Deferribacteres in DEHP-exposed mice. Spearman's correlation analysis showed that Bacteroidetes, Deferribacteres , and Firmicutes were associated with DEHP-induced testicular damage. In addition, the ratio of Firmicutes to Bacteroidetes (Firm/Bac ratio) significantly decreased from 0.28 (control group) to 0.13 (DEHP-exposed group), which was restored by L. plantarum TW1-1 treatment. Correlation analysis showed that the Firm/Bac ratio was negatively correlated with testicular damage and inflammation. These findings suggest that L. plantarum TW1-1 prevents DEHP-induced testicular damage via modulating gut microbiota and decreasing inflammation.

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Section: Discussionmentioning

confidence: 95%

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

Tian

Feng

et al. 2019

Front. Cell. Infect. Microbiol.

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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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“…Some phthalates are developmental and reproductive toxins that modulate endogenous fetal testicular testosterone production [ 28 ]. Studies in mice suggest that others, such as DEHP or MEHP, are potential human carcinogens [ 18 – 20 , 26 ]. DEHP can be found in building and construction materials, clothing, furnishings, toys, and food or medical contact materials.…”

Section: Discussionmentioning

confidence: 99%

“…Several groups have reported the effects of phthalates on reproductive toxicity, liver damage, and carcinogenesis, but phthalate mechanisms of action in tumorigenesis, tumor progression, and drug resistance are still unclear [ 18 – 26 ]. This study evaluated serum DEHP/MEHP levels in colon cancer patients, and found that DEHP/MEHP concentrations increased with cancer stage.…”

Section: Introductionmentioning

confidence: 99%

Phthalate exposure promotes chemotherapeutic drug resistance in colon cancer cells

et al. 2017

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Phthalates are widely used as plasticizers. Humans can be exposed to phthalates through ingestion, inhalation, or treatments that release di(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono(2-ehylhexyl) phthalate (MEHP), into the body from polyvinyl chloride-based medical devices. Phthalate exposure may induce reproductive toxicity, liver damage, and carcinogenesis in humans. This study found that colon cancer cells exposed to DEHP or MEHP exhibited increased cell viability and increased levels of P-glycoprotein, CD133, Bcl-2, Akt, ERK, GSK3β, and β-catenin when treated with oxaliplatin or irinotecan, as compared to control. The P-glycoprotein inhibitor, tariquidar, which blocks drug efflux, reduced the viability of DEHP- or MEHP-treated, anti-cancer drug-challenged cells. DEHP or MEHP treatment also induced colon cancer cell migration and epithelial-mesenchymal transformation. Elevated stemness-related protein levels (β-catenin, Oct4, Sox2, and Nanog) and increased cell sphere sizes indicated that DEHP- or MEHP-treated cells were capable of self-renewal. We also found that serum DEHP concentrations were positively correlated with cancer recurrence. These results suggest phthalate exposure enhances colon cancer cell metastasis and chemotherapeutic drug resistance by increasing cancer cell stemness, and that P-glycoprotein inhibitors might improve outcomes for advanced or drug-resistant colon cancer patients.

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Effects of di(2-ethylhexyl)phthalate exposure on 1,2-dimethyhydrazine-induced colon tumor promotion in rats

Cited by 27 publications

References 44 publications

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

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

Phthalate exposure promotes chemotherapeutic drug resistance in colon cancer cells

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