Author(s): Wang T, Qiao S, Lei S, Liu Y, Ng KF, et al.
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.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/21912612
Author(s): Dhingra R, Vasan RS
Author(s): Fox KA, Bergmann SR, Sobel BE
Author(s): Luca MC, Liuni A, Muxel S, Münzel T, Forconi S, et al.
Author(s): Xia Z, Xia R, Lan HT, Luo T, Tang QZ, et al.
Author(s): Fan Q, Yang XC, Liu Y, Wang LF, Liu SH, et al.
Author(s): Huang Z, Zhong X, Irwin MG, Ji S, Wong GT, et al.
Author(s): Xia Z, Wang F, Luo T
Author(s): Gong JS, Yao YT, Fang NX, Huang J, Li LH
Author(s): Liu C, Dai R, Yu R, Xu J
Author(s): Nie R, Zhong X, Xia Z
Author(s): Balakumar P, Sharma NK
Author(s): Tai W, Shi E, Yan L, Jiang X, Ma H, et al.
Author(s): Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC
Author(s): Buja LM
Author(s): Kim DH, Kim YJ, Chang SA, Lee HW, Kim HN, et al.
Author(s): Greer EL, Brunet A
Author(s): Vogt PK, Jiang H, Aoki M
Author(s): Maiese K, Chong ZZ, Shang YC, Hou J
Author(s): Sengupta A, Molkentin JD, Paik JH, DePinho RA, Yutzey KE
Author(s): Zhao X, Gan L, Pan H, Kan D, Majeski M, et al.
Author(s): Van Der Heide LP, Hoekman MF, Smidt MP
Author(s): Oellerich MF, Potente M
Author(s): Ferdous A, Battiprolu PK, Ni YG, Rothermel BA, Hill JA
Author(s): Ronnebaum SM, Patterson C
Author(s): Battiprolu PK, Hojayev B, Jiang N, Wang ZV, Luo X, et al.
Author(s): Puthanveetil P, Zhang D, Wang Y, Wang F, Wan A, et al.
Author(s): Puthanveetil P, Wang Y, Wang F, Kim MS, Abrahani A, et al.
Author(s): Puthanveetil P, Wang Y, Zhang D, Wang F, Kim MS, et al.
Author(s): Miki T, Itoh T, Sunaga D, Miura T
Author(s): Akiyama N, Okumura K, Watanabe Y, Hashimoto H, Ito T, et al.
Author(s): Nakada T, Kwee IL
Author(s): Depre C, Vanoverschelde JL, Taegtmeyer H
Author(s): Wijns W, Vatner SF, Camici PG
Author(s): Leung AA, Eurich DT, Lamb DA, Majumdar SR, Johnson JA, et al.
Author(s): Huffmyer J, Raphael J
Author(s): Tremblay ML, Giguère V
Author(s): Steinberg SF
Author(s): Furuyama T, Kitayama K, Yamashita H, Mori N
Author(s): Ding M, Rzucidlo EM, Davey JC, Xie Y, Liu R, et al.
Author(s): Gross DN, van den Heuvel AP, Birnbaum MJ
Author(s): Marfella R, Di Filippo C, Esposito K, Nappo F, Piegari E, et al.
Author(s): Tzivion G, Dobson M, Ramakrishnan G
Author(s): Kim MS, Wang F, Puthanveetil P, Kewalramani G, Innis S, et al.
Author(s): Parisi Q, Biondi-Zoccai GG, Abbate A, Santini D, Vasaturo F, et al.
Author(s): Andrews NP, Prasad A, Quyyumi AA
Author(s): Brunet J, Boily MJ, Cordeau S, Des Rosiers C
Author(s): Hsu CP, Zhai P, Yamamoto T, Maejima Y, Matsushima S, et al.
Author(s): Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, et al.
Author(s): Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, et al.
Author(s): Mehra A, Shotan A, Ostrzega E, Hsueh W, Vasquez-Johnson J, et al.
Author(s): Bauters C, Lamblin N, Mc Fadden EP, Van Belle E, Millaire A, et al.
Author(s): Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, et al.
Author(s): Kok BP, Brindley DN
Author(s): Philip-Couderc P, Tavares NI, Roatti A, Lerch R, Montessuit C, et al.
Author(s): Xuan YT, Guo Y, Han H, Zhu Y, Bolli R
Author(s): Tsang A, Hausenloy DJ, Mocanu MM, Carr RD, Yellon DM
Author(s): Zhan L, Wang T, Li W, Xu ZC, Sun W, et al.
Author(s): Somers SJ, Frias M, Lacerda L, Opie LH, Lecour S