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COX-2 inhibitor protects rat heart against oxidative stress through a pathway independent of cyclooxygenase
Authors:LV Ping-ping  CHEN Ying-ying  SHEN Yue-liang  ZHU Li
Institution:Department of Physiology,Zhejiang University School of Medicine,Hangzhou 310058,China.E-mail:bchenyy@zju.edu.cn
Abstract:AIM: To investigate whether nimesulide [a selective cyclooxygenase 2 (COX-2) inhibitor] and piroxicam (an inhibitor of COX-1) protect the rat hearts against oxidative stress induced by hydrogen peroxide,superoxide anion or hydroxyl free radical.METHODS: Cardiac contractility,lactate dehydrogenase (LDH) and malondialdehyde (MDA) were analyzed by the Langendorff method in isolated rat hearts.Production of 6-Keto-PGF1α,a marker of COX activity,was measured in isolated rat hearts.RESULTS: Rat hearts were exposed to hydrogen peroxide (H2O2),pyrogallol (which produced superoxide anion) or Vit C+Fe2+ (which produced hydroxyl free radical) for 10 min followed by reperfusion for 30 min.H2O2 decreased cardiac contractility and increased LDH release,which was inhibited by nimesulide (3 mg/kg) [LVDP 72%±10% vs 61%±11%,LDH (5.5±2.5)U/L vs (8.0±2.1)U/L,P<0.05].Piroxicam (3 mg/kg) increased systolic function (LVDP 73%±10% vs 61%±11%,P<0.05),but exacerbated diastolic function [LVEDP (29.00±5.61)mmHg vs (23.16±3.57) mmHg,P<0.01] in H2O2 treated rat hearts.Nimesulide also protected rat hearts against superoxide anion and hydroxyl free radical injury.Nimesulide and piroxicam had no effect on the content of 6-Keto-PGF in rat hearts.Mitochondrial ATP sensitive potassium channel (mitoKATP) inhibitor 5-HD blocked the improvement of contractility (LVDP and ±dp/dtmax) induced by nimesulide in H2O2 treated rat hearts (53%±12% vs 69%±3%,58%±11% vs 72%±7% and 37%±8% vs 51%±4% respectively,P<0.01).CONCLUSION: The results suggests that COX-2 inhibitor nimesulide can protect rat hearts against oxidative injury.The protection is independent of COX activity.Activation of mitoKATP may be involved in nimsulide-induced cardioprotection in rat hearts.
Keywords:Oxidative stress  Cyclooxygenase inhibitors  
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