Comparison of the Protective Effect of N-Acetylcysteine by Different Treatments on Rat Myocardial Ischemia-Reperfusion Injury

Journal of Pharmacological Sciences

Satoshi Ichimaru²  Koichiro Wada¹  Masahiro Abe²  Koichiro Tsuchiya²  Yoshiharu Takiguchi² 

[1] Department of Pharmacology, Graduate School of Dentistry, Osaka University, Japan;Department of Clinical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan

关键词: N-acetylcysteine;    myocardial ischemia/reperfusion injury;    oxidative stress;    continuous infusion;    bolus injection;   

DOI  :  10.1254/jphs.FP0071664

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(28)Cited-By(22)Reactive oxygen species have been known as important contributors to ischemia/reperfusion (I/R) injury. Studies on the beneficial effect of N-acetylcysteine (NAC), a potent antioxidant, on limiting infarct size induced by I/R yielded contrasting results. The present study was undertaken to compare the effect of NAC by different administration methods on infarct size in a rat myocardial I/R model. Rats underwent 30 min of left coronary occlusion followed by 4 h of reperfusion. Treatment with continuous infusion of NAC (150 mg/kg per hour) from 30 min before occlusion for 2 h (until 1 h after the start of reperfusion) produced a significant limitation of the infarct size as a percentage of the ischemic area (8%) compared to the non-treated control (60%). However, bolus injection of 150 mg/kg at 30 min prior to occlusion and 5 min prior to reperfusion failed to reduce it (56%) although the total dose is the same. The decreased total glutathione content and glutathione peroxidase activity in the ischemic region were recovered in the continuous infusion group, but not in the bolus injection group. The increased myeloperoxidase activity and phosphorylation of inhibitor κB after I/R were inhibited by the continuous treatment. These results indicate that the protective effect of NAC on myocardial infarction induced by I/R was different depending on the administration method. It is necessary to maintain blood concentration during the early period of reperfusion to obtain the beneficial effect of NAC.

【 授权许可】

Unknown