title: N-Acetylcysteine Restores Sevoflurane Postconditioning Cardioprotection against Myocardial Ischemia-Reperfusion Injury in Diabetic Rats.
abstract: The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou 510642, China.
authors.forename: Jiefu
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong; Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou 510642, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou 510642, China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Haobo
authors.identifier: 0000-0002-5660-7835
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Michael G
authors.identifier: 0000-0001-5801-274X
authors.initials: MG
authors.lastname: Irwin
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong; Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524023, China.
authors.forename: Zhengyuan
authors.identifier: 0000-0002-7002-5524
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018955:CD36 Antigens / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000077149:Sevoflurane; D013997:Time Factors; D019210:Troponin I / Q000097:blood; D000071161:Forkhead Box Protein O1
chemical_list: D000111:Acetylcysteine; D052242:Adiponectin; D000975:Antioxidants; D018955:CD36 Antigens; D052279:Creatine Kinase, MB Form; D051858:Forkhead Transcription Factors; D008738:Methyl Ethers; D009419:Nerve Tissue Proteins; D050796:STAT3 Transcription Factor; D000077149:Sevoflurane; D019210:Troponin I; C499920:Adipoq protein, rat; C494088:Stat3 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1