The role of oxidative stress in DNA damage in pancreatic β cells induced by di-(2-ethylhexyl) phthalate. (1st March 2017)

• Record Type: Journal Article
• Authors: She, Yan; Jiang, Liping; Zheng, Liangliang; Zuo, Heming; Chen, Min; Sun, Xiance; Li, Qiujuan; Geng, Chengyan; Yang, Guang; Jiang, Lijie; Liu, Xiaofang
• Is Part Of: Chemico-biological interactions. Volume 265(2017)
• Page Start: 8
• Page End: 15
• Publication Date: 2017-03-01
• Subjects: Di(2-ethyhexyl) phthalate -- Oxidative DNA damage -- PQQ -- Oxidative stress -- Insulin Resistance; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.01.015
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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. Highlights: 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.