Oleuropein attenuates the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-perturbing effects on pancreatic β-cells

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting compound and persistent organic pollutant that has been associated with diabetes in several epidemiological studies. Oleuropein, a major phenolic compound in olive fruit, is a superior antioxidant and radical scavenger. This study aimed to examine the effects of oleuropein against TCDD-induced stress response in a pancreatic beta cell line, INS-1 cells. Cells were pre-incubated with various concentrations of oleuropein and then stimulated with TCDD (10 nM) for 48 hrs. When treated with TCDD, INS-1 cells produced robust amounts of prostaglandin E₂ (PGE₂) compared to the untreated control, and this increase was inhibited by oleuropein treatment. TCDD increased Ca²⁺-independent phospholipase A₂ (iPLA₂β) level, but had no effect on Group 10 secretory phospholipase A₂ (PLA₂G10) level, while oleuropein deceased the levels of iPLA₂β and PLA₂G10 in the presence of TCDD. Cyclooxygenase-1 (COX-1) was significantly increased by TCDD treatment and attenuated with oleuropein pretreatment. Oleuropein decreased TCDD-mediated production of JNK, TNF-α, and ROS. In addition, oleuropein increased Akt and GLUT2 levels suppressed by TCDD in INS-1 cells. Thus, the results suggest that oleuropein prevents pancreatic beta cell impairment by TCDD.

Keywords:

• 2378-Tetrachlorodibenzo-p-dioxin
• oleuropein
• prostaglandin E2
• phospholipase A2
• cytokines

Conflict of interest

The authors did not report any conflict of interest.

Additional information

Funding

This research was funded by the Korea Centers for Disease Control and Prevention, grant number 2020-ER6402-00.