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Article: N-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats

TitleN-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 8 How to Cite?
AbstractBackground: 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. © 2011 Wang et al.
Persistent Identifierhttp://hdl.handle.net/10722/138931
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council (RGC) of Hong Kong781109 M
766709 M
784011
Funding Information:

This work was supported by Research Grants Council (RGC) of Hong Kong GRF grants (781109 M, 766709 M and 784011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorWang, Ten_HK
dc.contributor.authorQiao, Sen_HK
dc.contributor.authorLei, Sen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorNg, KFJen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorIrwin, MGen_HK
dc.contributor.authorXia, Zen_HK
dc.date.accessioned2011-09-23T05:42:17Z-
dc.date.available2011-09-23T05:42:17Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 8en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138931-
dc.description.abstractBackground: 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. © 2011 Wang et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAcetylcysteine - pharmacology - therapeutic use-
dc.subject.meshAdiponectin - biosynthesis - metabolism-
dc.subject.meshAllopurinol - pharmacology - therapeutic use-
dc.subject.meshAntioxidants - pharmacology - therapeutic use-
dc.subject.meshDiabetes Complications - drug therapy - metabolism - pathology - physiopathology-
dc.titleN-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic ratsen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, KFJ:jkfng@hkucc.hku.hken_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL:ksllam@hku.hken_HK
dc.identifier.emailIrwin, MG:mgirwin@hku.hken_HK
dc.identifier.emailXia, Z:zyxia@hkucc.hku.hken_HK
dc.identifier.authorityNg, KFJ=rp00544en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityIrwin, MG=rp00390en_HK
dc.identifier.authorityXia, Z=rp00532en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0023967en_HK
dc.identifier.pmid21912612-
dc.identifier.pmcidPMC3166050-
dc.identifier.scopuseid_2-s2.0-80052290747en_HK
dc.identifier.hkuros193496en_US
dc.identifier.hkuros213328-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052290747&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue8en_HK
dc.identifier.spagee23967-
dc.identifier.epagee23967-
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000294678300014-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, T=51664012300en_HK
dc.identifier.scopusauthoridQiao, S=51663861100en_HK
dc.identifier.scopusauthoridLei, S=35208515200en_HK
dc.identifier.scopusauthoridLiu, Y=37115892000en_HK
dc.identifier.scopusauthoridNg, KFJ=13608809400en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridIrwin, MG=7202411076en_HK
dc.identifier.scopusauthoridXia, Z=7402151748en_HK

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