Pharmacological preconditioning with resveratrol:  an insight with iNOS knockout mice

Imamura, Gembu; Bertelli, A.; Bertelli, A. A. E.; Otani, Hajime; Maulik, Nilanjana; Das, Dipak K.

doi:10.1152/ajpheart.01013.2001

Cited by 118 publications

(96 citation statements)

References 30 publications

(33 reference statements)

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“…For instance, iNOS has been suggested to contribute to burn injury-induced muscle apoptosis and atrophy leading to p53 activation and upregulation (Sugita et al, 2012). iNOS inhibition genetically and/or pharmacologically, indeed, results in the reduction of the ongoing apoptosis (Heneka et al, 1999;Imamura et al, 2002;Miyazawa et al, 2003;Kiang et al, 2008). Thus, it can be concluded that p53 overexpression in the gastrocnemius muscle might be resulting from the increased iNOS expression shown in our previous study (Erekat et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Erekat

2015

The Anatomical Record

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Apoptosis has been implicated in the pathogenesis of Parkinson disease (PD). Parkinson disease is characterized by skeletal muscle abnormalities. The aim of this study is to illustrate the impact of PD induction on the expression of apoptotic mediators. Twenty normal albino mice were randomly selected and equally divided in control and PD groups. Chronic Parkinsonism was induced in the PD group using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p). After that, samples from gastrocnemius muscles were evaluated by immunohistochemistry to examine the expression of p53 and active caspase-3 in the two groups of animals. P53 and active caspase-3 expression was significantly higher in gastrocnemius skeletal muscle in PD mice compared with that in the control mice (P value <0.01). Furthermore, we show PD gastrocnemius muscle atrophy measured by significant reduction (P < 0.01) in the muscle fiber cross-sectional area. Thus, our present data suggest that PD induction increased the expression of the apoptotic mediators p53 and active caspase-3 in gastrocnemius muscle, indicating the induction of apoptosis, which was correlative with gastrocnemius muscle atrophy subsequent to the induction of PD.

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Section: Discussionmentioning

confidence: 99%

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Erekat

2015

The Anatomical Record

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“…The beneficial effect of resveratrol on coronary artery disease may be due to its ability to retard the progression of early atherosclerotic lesions. Our previous reports demonstrated significant reduction in oxidative stress and upregulation of inducible nitric oxide synthase (iNOS) mRNA expression leading to the reduction of cardiomyocyte apoptosis by resveratrol [7]. Recent report from our laboratory has also documented the cardioprotective effect of resveratrol in vivo as well as in vitro which operates through the increased induction of thioredoxin (Trx-1), heme oxygenase (HO-1) and vascular endothelial growth factor (VEGF).…”

Section: Introductionmentioning

confidence: 93%

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

Penumathsa

Thirunavukkarasu

Koneru

et al. 2007

Journal of Molecular and Cellular Cardiology

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152

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Hypercholesterolemia (HC) is a common health problem that significantly increases risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated cardioprotection through nitric oxide dependent mechanism. Therefore the present study was undertaken to determine whether combination therapy with statin and resveratrol are more cardioprotective than individual treatment groups in ischemic rat heart model. The rats were fed rats with 2% high cholesterol diet and after 8 weeks of high cholesterol diet the animals were treated with statin (1mg/kg bw/day) and resveratrol (20mg/kg bw/day) for 2 weeks. The rats were assigned to: 1) Control (C) 2) HC 3) HCR 4) HCS and 5) HCRS. The hearts, subjected to 30 min global ischemia followed by 120 min reperfusion were used as experimental model. The left ventricular functional recovery (+dp/dt) was found to be significantly better in the HCRS (1926±43), HCR (1556±65) and HCS (1635±40) compared to HC group (1127±16). The infarct size in the HCRS, HCS and HCR groups were 37±3.6, 43±3.3 and 44 ±4.2 respectively compared to 53±4.6 in HC. The lipid level was found to be decreased in all the treatment groups when compared to HC more significantly in HCS and HCRS groups when compared to HCR. Increased phosphorylation of Akt and eNOS was also observed in all the treatment groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of reduction in apoptosis was more significant in HCRS group compared to all other groups. In-vivo rat myocardial infarction (MI) model subjected to one week of permanent left descending coronary artery (LAD) occlusion documented increased capillary density in HCR and HCRS treated group when compared to HCS treatment group. We also documented increased β-catenin translocation and increased VEGF mRNA expression in all treatment groups. Thus, we conclude that the acute as well as chronic protection afforded by combination treatment with statin and resveratrol may be due to pro-angiogenic, antihyperlipidemic and anti-apoptotic effects and long term effects may be caused by increased neovascularization of the MI zone leading to less ventricular remodeling.

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“…37,38 Moreover, in iNOS knockout mice, the antoxidant resveratrol had no protective effects on attenuating cardiac injury, though it protected against cardiac damage in wild-type mice, supporting a protective role of iNOS-related NO as an antioxidant. 39 NO formation through increased NOS activity should be an important protective mechanism during kallistatin treatment after MI injury.…”

Section: Cardioprotection By Kallistatin Via Antioxidation L Gao Et Almentioning

confidence: 99%

Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction

Gao

Yin

Smith

et al. 2008

Laboratory Investigation

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Oxidative stress causes cardiomyocyte death and subsequent ventricular dysfunction and cardiac remodeling after myocardial infarction (MI), thus contributing to high mortality in chronic heart failure patients. We investigated the effects of kallistatin in cardiac remodeling in a chronic MI rat model and in primary cardiac cells. Human kallistatin gene was injected intramyocardially 20 min after ligation of the left coronary artery. At 4 weeks after MI, expression of human kallistatin in rat hearts was identified by reverse transcription-polymerase chain reaction, immunohistochemistry and ELISA. Kallistatin administration improved cardiac performance, increased mean arterial pressure, decreased myocardial infarct size and restored left ventricular wall thickness. Kallistatin treatment significantly attenuated cardiomyocyte size and atrial natriuretic peptide expression. Kallistatin also reduced collagen accumulation, collagen fraction volume and expression of collagen types I and III, transforming growth factor-b1 (TGF-b1) and plasminogen activator inhibitor-1 in the myocardium. Inhibition of cardiac hypertrophy and fibrosis by kallistatin was associated with increased cardiac nitric oxide (NO) levels and decreased superoxide formation, NADH oxidase activity and p22-phox expression. Moreover, in both primary cultured rat cardiomyocytes and myofibroblasts, recombinant kallistatin inhibited intracellular superoxide formation induced by H 2 O 2 , and the antioxidant effect of kallistatin was abolished by No-nitro-L-arginine methyl ester (L-NAME), indicating a NO-mediated event. Kallistatin promoted survival of cardiomyocytes subjected to H 2 O 2 treatment, and inhibited H 2 O 2 -induced Akt and ERK phosphorylation, as well as NF-kB activation. Furthermore, kallistatin abrogated TGF-b-induced collagen synthesis and secretion in cultured myofibroblasts. This is the first study to demonstrate that kallistatin improves cardiac performance and prevents post-MI-induced cardiac hypertrophy and fibrosis through its antioxidant action. Myocardial infarction (MI) leads to cardiac remodeling with complex structural alterations. After an ischemic insult, left ventricle (LV) enlargement is followed by progressive diastolic stiffness, enhanced wall stress and oxygen consumption, thus resulting in cardiomyocyte hypertrophy, interstitial fibrosis and decreased cardiac output. Increased reactive oxygen species (ROS) levels are recognized to be involved in ischemic heart failure and considered to be a major cause of cardiomyocyte death, ventricular dysfunction and heart failure progress. 1 Under pathological conditions, increased oxidative stress damages DNA and mitochondrial function, activates proapoptotic signaling kinases and leads to myocyte apoptosis or necrosis. 2,3 Elevation of ROS activates a series of hypertrophic signaling kinases and transcription factors to stimulate cardiac hypertrophy. 3,4 Moreover, ROS stimulate fibroblast proliferation and activate the expression of profibrotic factors, including transforming growth...

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Pharmacological preconditioning with resveratrol: an insight with iNOS knockout mice

Cited by 118 publications

References 30 publications

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction

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