Telmisartan, a dual ARB/partial PPAR-γ agonist, protects myocardium from ischaemic reperfusion injury in experimental diabetes

Goyal, Sameer N.; Bharti, Sudhakar; Bhatia, Jagriti; Nag, Tapas Chandra; Ray, Ruma; Arya, Dharamvir Singh

doi:10.1111/j.1463-1326.2011.01377.x

Cited by 49 publications

(53 citation statements)

References 38 publications

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“…Reactive oxygen species which are highly toxic by-products of aerobic metabolism are known to act in response widely to cellular membranes and macromolecules; thus, pretty formation of lipid peroxides culminates into tissue damage [79]. The augmented echelon of MDA observed in the present study following ISO treatment might be due to free radical scavenging membrane damage [61]. Result of the present study shows that treatment with AP significantly normalized the MDA.…”

Section: Discussionmentioning

confidence: 71%

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Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System

2015

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Apigenin (AP) is a flavone in dietary flavonoids reported as strong antioxidant and elite modulator of PPARγ. The current study evaluated the consequence of AP in isoproterenol (ISO)-induced oxidative stress and myocardial infarction during β-adrenergic receptor stimulus in rats by persistent hemodynamic, biochemical and histopathological changes. Rats received AP (25, 50 and 75 mg/kg/day) or vehicle i.p. for 14 days and ISO (100 mg/kg, s.c.) on 13th and 14th days for initiation of cardiotoxicity. ISO-treated rats showed evidence of significant dwindle in systolic and diastolic arterial pressures, maximal positive rate of developed left ventricular pressure. In totting up, a noteworthy diminution in activities of creatine kinase-MB isoenzyme, reduced glutathione, superoxide dismutase, catalase and level along with rise in malondialdehyde content were observed. The shielding function of AP on isoproterenol-induced myocardial damage was observed by attenuating all the endogenous parameters and the membrane-bound enzymes. It was confirmed by histopathological examinations. The effect of AP at the doses of 50 and 75 mg/kg showed added apparent than at the dose of 25 mg/kg. Current study thus provides confirmation for protective effects of AP on myocardium in experimentally induced myocardial infarction.

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Section: Discussionmentioning

confidence: 71%

“…Myocardial infarction is related to various deleterious symptoms or conditions, which led to damage the cardiac tissues and showed abnormality in the membrane-bound protective guards present in the myocardium. Such as failure of antioxidant mechanisms, cell necrosis in rats and increases the oxidative stress in the myocardium [59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System

2015

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“…10,11 The pathologist performing histopathological and ultrastructural analyses was blinded to the treatment protocol. The degree of necrosis was graded and scored as follows.…”

Section: Histological and Ultrastructural Evaluationmentioning

confidence: 99%

“…Hemodynamic indices such as mean arterial pressure (MAP) and heart rate (HR) and left ventricular function indices such as left ventricular end-diastolic pressure (LVEDP), maximum rate of pressure development (+LVdP/dt max ), and pressure decline (2LVdP/dt max ) were recorded by the method described previously. 10,11 At the end of the reperfusion period, blood samples were withdrawn from the heart, and the serum was separated by centrifugation (Heraeus Biofuge, Germany) at 3000g for 5 minutes and analyzed for CK-MB activity and TNF-a level. Subsequently, all the animals were killed, and their hearts were excised and processed for biochemical, histopathological, ultrastructural, and molecular studies.…”

Section: Surgical Procedures and Assessment Of Hemodynamic Functionsmentioning

confidence: 99%

In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS

Malik

Sharma

Bharti

et al. 2011

Journal of Cardiovascular Pharmacology

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Recent studies have uncovered the beneficial effects of statin in cardiovascular diseases; however, the role of pitavastatin in ischemia-reperfusion (IR)-induced apoptosis and myocardial damage is not established. Therefore, in this study, we aim to investigate whether pitavastatin treatment attenuates myocardial IR injury via regulating oxidative stress, inflammation, apoptosis, and phosphorylated protein kinase B (pAkt) endothelial nitric oxide synthase (e-NOS) pathways. After the 14-day treatment with pitavastatin (0.16-0.64 mg·kg·d, po) or saline, rats were subjected to 45 minutes of ischemia by occluding the left anterior descending coronary artery and to 60 minutes of reperfusion to induce myocardial damage. Pitavastatin at a dose of 0.32 and 0.64 mg/kg significantly improved cardiac function as evidenced by the normalization of the mean arterial pressure, heart rate, ±LVdP/dtmax, and left ventricular end-diastolic pressure as compared with the IR control. Additionally, pitavastatin dose-dependently normalized myocardial antioxidants, lactate dehydrogenase, and thiobarbituric acid reactive substances along with decreased serum tumor necrosis factor-α level and creatine kinase isoenzyme-MB activity. Furthermore, pitavastatin enhanced pAkt, (p) e-NOS, Bcl-2, and suppressed IκB kinase/nuclear factor-kappa B, nitrotyrosine (NO inactivation product), Bax, and capases-3 protein expression in the heart. Morphological assessments of the IR-challenged myocardium showed that 0.32 and 0.64 mg/kg of pitavastatin decrease myocardial necrosis and inflammatory changes. Thus, pitavastatin reduced IR-induced infarction and dysfunction via the augmentation of endogenous antioxidant, suppression of IκB kinase/nuclear factor-kappa B, activation of pAkt-e-NOS, and/or decreased NO inactivation and apoptosis.

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“…21,22 Although some experiments have suggested a protective effect of angiotensin-converting enzyme inhibition or ARB therapy early during ischemic-reperfusion kidney injury, outcomes with these agents have not been uniformly favorable. [23][24][25][26] One concern with these treatments is the risk of hemodynamic insult related to an acute lowering of glomerular filtration pressure. These studies, therefore, parse the mechanisms underpinning the mixed effects of global RAS inhibition during cisplatin-induced AKI by defining the distinct roles of AT 1 receptors on T cells and kidney epithelial cells in this setting and documenting the critical contribution of TNF in the distal nephron to cisplatin nephrotoxicity.…”

mentioning

confidence: 99%

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI

Zhang¹,

Rudemiller²,

Patel³

et al. 2016

JASN

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Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT 1 ) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-a is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-a is suppressed or enhanced by AT 1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT 1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-a levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT 1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-a production induced by cisplatin. Finally, disrupting TNF-a production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-a levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT 1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

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Telmisartan, a dual ARB/partial PPAR-γ agonist, protects myocardium from ischaemic reperfusion injury in experimental diabetes

Abstract: In addition to the class effect of ARBs, telmisartan has a beneficial effect in I/R injury in diabetic rats in part because of activation of PPAR-γ.

Cited by 49 publications

References 38 publications

Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System

Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System

In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI

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