Probucol Prevents Atrial Remodeling by Inhibiting Oxidative Stress and TNF-α/NF-κB/TGF-β Signal Transduction Pathway in Alloxan-Induced Diabetic Rabbits.
Probucol Prevents Atrial Remodeling Introduction Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms for the increased propensity for AF in the setting of DM and the potential effects of probucol on atrial remodeling remain unclear. M...
| Publicado en: | Journal of Cardiovascular Electrophysiology Vol. 26; no. 2; pp. 211 - 223 |
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| Autores principales: | , , , , , , |
| Formato: | diagnostic images pictorial research tables/charts tracings Journal Article |
| Publicado: |
Wiley-Blackwell
Feb2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=100883740&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 100883740 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10453873 GSB jtl: Journal of Cardiovascular Electrophysiology issn: 10453873 maglogo: Y pubinfo: dt: Feb2015 vid: 26 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 100883740 103755895 103755895 10.1111/jce.12540 100883740 ppf: 211 ppct: 12 formats: fmt: @attributes: type: P tig: atl: Probucol Prevents Atrial Remodeling by Inhibiting Oxidative Stress and TNF-α/NF-κB/TGF-β Signal Transduction Pathway in Alloxan-Induced Diabetic Rabbits. aug: au: FU, HUAYING LI, GUANGPING LIU, CHANGLE LI, JIAN WANG, XINGHUA CHENG, LIJUN LIU, TONG affil: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University sug: subj: Phenols Administration and Dosage Oxidative Stress Tumor Necrosis Factor Drug Effects NF-kappa B Drug Effects Growth Substances Drug Effects Signal Transduction Drug Effects Heart Atrium Drug Effects Animal Studies Rabbits Descriptive Statistics Random Assignment Heterocyclic Compounds Administration and Dosage Diabetes Mellitus Chemically Induced Atrial Fibrillation Risk Factors Diabetes Mellitus Complications Malondialdehyde Analysis Superoxide Dismutase Analysis Oxidoreductases Analysis Blotting, Western China Hemodynamics Electrophysiology Echocardiography Tissue Culture Techniques Data Analysis Software Polymerase Chain Reaction Fisher's Exact Test One-Way Analysis of Variance Funding Source ab: Probucol Prevents Atrial Remodeling Introduction Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms for the increased propensity for AF in the setting of DM and the potential effects of probucol on atrial remodeling remain unclear. Methods and Results Eighty Japanese rabbits were randomly assigned to normal/control group (Control, n = 20), alloxan-induced diabetic group (DM, n = 20), probucol-treated group (Control-P, n = 20), and probucol-treated diabetic group (DM-P, n = 20). Rabbits in the DPR and CPR groups were orally administered probucol (1,000 mg/day) for 8 weeks. Serum and left atrial tissue malonaldehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), and catalase (CAT) levels were assessed. Isolated Langendorff perfused rabbit hearts were prepared to evaluate atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial conduction time (IACT), and vulnerability to AF. Atrial interstitial fibrosis was also evaluated. The mRNA expression levels of TNF-α and TLR4 were analyzed. The protein expressions of NF-κB, HSP70, TGF-β, and ERK in left atrial tissue were analyzed by Western blot. Probucol administration decreased the inducibility of AF in diabetic rabbits and attenuated atrial interstitial fibrosis. The DM-P rabbits exhibited significant alleviation of oxidative stress, evidenced by reduced serum and tissue MDA, compared with diabetic rabbits. Moreover, NF-κB, TGF-β, and HSP70 protein expression and TNF-α mRNA expression were significantly downregulated by probucol treatment in alloxan-induced diabetic rabbits. Conclusions Probucol prevents atrial remodeling and suppresses AF development in alloxan-induced diabetic rabbits. Its inhibitory effects on oxidative stress, NF-κB, TGF-β, and TNF-α overexpression may contribute to its antiremodeling effects. pubtype: Academic Journal doctype: diagnostic images pictorial research tables/charts tracings Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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