Synergistically protective effects of metformin and liraglutide on endothelial cell oxidative damage induced by palmitic acid

Abstract

Objective To investigate whether metformin and liraglutide had a synergistically protective effects on palmitic acid-induced endothelial cell oxidative damage. Methods Human umbilical endothelial cell, which were exposed to palmitic acid for inducing endothelial cell dysfunction, were treated with metformin and/or liraglutide for 24 h. Intracellular level of reactive oxygen species (ROS) was detected by flow cytometry. Supernatant nitric oxide (NO) concentration was measured by nitrate reductase method. One-way ANOVA and Q test were applied to analyze the differences among the groups. Results Compared with control group, 0.25 and 0.50 mmol/L palmitic acid significantly increased intracellular ROS levels ((125±17)%, (189±8)% vs 100%, P<0.05), and decreased supernatant NO levels ((89.9±6.2)%, (79.8±4.8)% vs 100.0%, P<0.05). Either metformin (0.5-1.0 mmol/L) or liraglutide (10-100 nmol/L) treatment alone could significantly prevent the augmented ROS levels and reduced NO levels induced by 0.5 mmol/L palmitic acid. Mono-treatment with low dose of metformin (0.1 mmol/L) or liraglutide (3 nmol/L) did not alter the effects of 0.5 mmol/L palmitic acid on ROS and NO production. However, combination treatment with these doses of the agents significantly prevented the increased ROS levels and decreased NO levels induced by 0.5 mmol/L palmitic acid, shown as decrease of ROS level ((158±31)% vs (250±27)%, P<0.05) and increase of NO level ((91.7±30.6)% vs (82.3±5.0)%, P<0.05). Conclusion Metformin and liraglutide have a synergistic effects in protecting endothelial cell from palmitic acid-induced oxidative damage. Key words: Metformin; Liraglutide; Endothelial cells; Oxidative stress