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Chem Biol Interact. 2017 Mar 1;265:8-15. doi: 10.1016/j.cbi.2017.01.015. Epub 2017 Jan 20.

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

Author information

1
Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
2
Preventive Medicine Laboratory, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
3
Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Department of Occupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
4
Preventive Medicine Laboratory, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
5
Department of Internal Medicine, The Affiliated Zhong Shan Hospital of Dalian University, Dalian 116001, Liaoning, PR China.
6
Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China. Electronic address: food@dlmedu.edu.cn.

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.

KEYWORDS:

Di(2-ethyhexyl) phthalate; Insulin Resistance; Oxidative DNA damage; Oxidative stress; PQQ

PMID:
28115068
DOI:
10.1016/j.cbi.2017.01.015
[Indexed for MEDLINE]

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