کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5559616 1561577 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The role of oxidative stress in DNA damage in pancreatic β cells induced by di-(2-ethylhexyl) phthalate
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
The role of oxidative stress in DNA damage in pancreatic β cells induced by di-(2-ethylhexyl) phthalate
چکیده انگلیسی


- Di(2-ethyhexyl) phthalate (DEHP) exerts DNA damage effects on INS-1 cells.
- Lysosomal-mitochondrial aixs pathway is likely to be an important event of DEHP-induced DNA damage.
- DEHP-induced DNA strand breaks could be mediated by oxidative stress.

Di(2-ethyhexyl) phthalate (DEHP) is commonly used as a plasticizer, which loosely binds to plastic materials and easily leaches out of these products and enters into the environment. Exposure to DEHP can impair pancreatic beta cells (INS-1 cells)function, which is associated with Insulin Resistance (IR) and type 2 diabetes. However, the mechanism of how DEHP leads to Insulin Resistance is unknown. Our results showed that the cell viability of INS-1 cells exposed to DEHP (0-1600 μM) were decreased in a concentration-dependent manner. DEHP caused significant increases of DNA migration and oxidative damage in INS-1 cells. Lysosomal membrane permeability was increased and mitochondrial membrane potential was reduced after INS-1 cells treated with DEHP. DEHP was also shown to induce ROS production and cause GSH depletion in INS-1 cells. DEHP brought a significant decrease in super oxide dismutase (SOD) and led to accumulation of malondialdehyde (MDA) in the INS-1 cells. DEHP increased significantly the expression of P53 and ATM gene of INS-1 cell at high dose levels. Simultaneously, Pyrroloquinoline Quinone (PQQ), an antioxidant, and alcohol were used in the study to determine their effects on DEHP-induced INS-1 cells damage. PQQ could protect the INS-1 cells from the damage induced by DEHP to some extent, while alcohol aggravated the toxic effects of DEHP. These results indicate that DEHP-mediated INS-1 cell dysfunction through a lysosomal-mitochondrial pathway, involving oxidative stress and p53 and ATM activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 265, 1 March 2017, Pages 8-15
نویسندگان
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