N-Acetylcysteine and Allopurinol Synergistically Enhance Cardiac Adiponectin Content and Reduce Myocardial Reperfusion Injury in Diabetic RatsReport as inadecuate




N-Acetylcysteine and Allopurinol Synergistically Enhance Cardiac Adiponectin Content and Reduce Myocardial Reperfusion Injury in Diabetic Rats - Download this document for free, or read online. Document in PDF available to download.

Background

Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin APN, an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine NAC and-or allopurinol ALP can attenuate APN deficiency and myocardial ischemia reperfusion MI-R injury in the early stage of diabetes.

Methodology-Principal Findings

Control or streptozotocin STZ-induced diabetic rats were either untreated C, D or treated with NAC 1.5 g-kg-day or ALP 100 mg-kg-day or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI-R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 AdipoR2, reduced phosphorylation of Akt, signal transducer and activator of transcription 3 STAT3 and endothelial nitric oxide synthase eNOS but increased IL-6 and TNF-α all P<0.05 vs. C. NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB CK-MB release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes.

Conclusions-Significance

NAC and ALP synergistically restore myocardial APN and AdipoR2 mediated eNOS activation. This may represent the mechanism through which NAC and ALP combination greatly reduces MI-R injury in early diabetic rats.



Author: Tingting Wang, Shigang Qiao, Shaoqing Lei, Yanan Liu, Kwok F. J. Ng, Aimin Xu, Karen S. L. Lam, Michael G. Irwin , Zhengyuan Xia

Source: http://plos.srce.hr/



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