Protective effects of G004 on vascular endothelial cells

Abstract

Abstract: AIM: To study the protective effects of a novel sulfonylureous compound 1-[4-[2-(4-bromobenze-nesulfonaminoethyl) phenylsufonyl]-3-(trans-4-methylcyclohexyl) urea, G004, on vascular endothelial cells.METHODS: They were determined for the effects of compound G (04 on cell viability, concentration of malon-dialdehyde (MDA, a main decomposed product in lipicperoxidation) and activity of superoxide dismutase (SODin supernatant of oxidative injury endothelial cell(ECV304) of human umbilical vein caused by hydrogen peroxide. The activity of reactive oxygen species (ROS)in rat blood plasma was examined. The mode of vascularendothelial cell injury in rats was established by a higdose of adrenaline in combination with cold-water irritation. Then, the influence of compound GOO4 on plateletaggregation, the content of 6-K-PGENA, TXB2 T-PA, PATin blood plasma was investigated. The permeability of Evans blue in aortic wall and the blood plasma content ofGMP140 were studied in rats with injured vascular endothelial cell resulted from histamine.RESULTS: The compound C004 significantly improved the structuralchange of ECV304 cells damaged by hydrogen peroxidele prodt of MDA, increased activity ofSOD and the rate of animate cells. The compounreduced the production of ROS in the blood plasma ofrats. Compound G% 04 not only enhanced PGL] T-PA re-lease but reduced TXA2 PAI and potently inhibitedplatelet aggregation. The compound G004 decreasedGMP140 secretion from endothelial cells and permeability of Evans blue through aortic wall in rats injured by hista-mine with dose-dependence.CONCLUSION: The com-pound G004 can maintain the integrity of vascular endo-thelia cells, remove the ROS, modulate the secretion of TXA2, PGI2,, t-PA, PAL derived from endothelial cells and inhibit the increase of GMP140. The compound G004 shows the protective effect on vascular endothelial cell.

Key words: G004, ECV304, ROS, PGI₂, TXA₂, GMP140

CLC Number:

R965.1

WU Guan-zhong, ZHANG Wen-ping, LV Zheng-bing, LIU Guo-qing. Protective effects of G004 on vascular endothelial cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(10): 1156-1161.

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