Aspirin Eugenol Ester Reduces H(2)O(2)-Induced Oxidative Stress of HUVECs via Mitochondria-Lysosome Axis

阿司匹林丁香酚酯通过线粒体-溶酶体轴降低H₂O₂诱导的HUVECs氧化应激

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Abstract

The oxidative stress of vessel endothelium is a major risk factor of cardiovascular disorders. Antioxidative stress drugs are widely used in cardiovascular therapy. Aspirin eugenol ester (AEE) is a new pharmaceutical compound synthesized by esterification reaction of aspirin with eugenols and possesses antioxidative activity. The present study was designed to investigate the mechanism how AEE protects human umbilical vein endothelial cells (HUVECs) from H(2)O(2)-induced oxidative stress. H(2)O(2) was given to the HUVECs with or without AEE pretreatment. Changes in the oxidative stress-related factors, including those related to the mitochondria-lysosome axis, were determined with Western blotting, cellular immunofluorescence, and enzyme activity test. The results showed that, in the HUVECs, 300 μM H(2)O(2) treatment significantly increased the apoptosis rate, MDA concentration, reactive oxygen species (ROS) production, mitochondrial membrane potential, expression of Bax and mature cathepsin D (CTSD), and activity of CTSD and Caspase3 (Cas3) but decreased the expression of Bcl2 and lysosomal membrane stability, while in the HUVECs pretreated with AEE, the above changes caused by either the stimulatory or the inhibitory effect of H(2)O(2) on the relevant factors were significantly reduced. AEE pretreatment significantly enhanced the activity of cellular superoxide dismutase and glutathione peroxidase in the HUVECs. Our findings suggest that AEE effectively reduced H(2)O(2)-induced oxidative stress in the HUVECs via mitochondria-lysosome axis.

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