Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine model of cardiomyopathy

Rashikh, Azhar; Ahmad, Shibli Jameel; Pillai, K. K.; Kohli, Kanchan; Najmi, Abul Kalam

doi:10.1016/j.biopha.2011.11.020

Cited by 29 publications

(25 citation statements)

References 40 publications

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“…These results are in agree with that found by Rashikh [7] whose study was planned to test the possible protective effects of aliskiren in 100 mg/kg/day for 42 days in a model of cardiomyopathy in rats. Their results revealed that the drug significantly preserved the antioxidant defense and increased some anti-oxidant markers like glutathione (GSH) and superoxide dismutase (SOD).…”

Section: Discussionsupporting

confidence: 82%

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Aliskiren Augments the Activities of Anti-Oxidant Enzymes in Liver Homogenates of DOCA Salt-Induced Hypertensive Rats

Kamal¹

2014

AER

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Hypertension is a serious problem that is recently thought to be associated with damaging effects on target organs partially via oxidative stress. On the other hand, there is accumulating literature describing some sort of therapeutic interaction between antioxidant enzymes in vital organs and hypertension. Therefore, the aim of this study is to investigate the possible effect of a direct renin inhibitor, aliskiren, used in treatment of hypertension via renin-angiotensin-aldosterone system (RAAS), on selected anti-oxidant enzymes in hepatic homogenates in DOCA salt-induced hypertesnive albino rats. Thirty male wister albino rats were assigned randomly into 3 groups (n = 10/ group). Group 1 received no treatement and serves as control. Group 2 received 0.5% carboxymethylcellulose sodium ip as a solvent of aliskiren, as a direct renin inhibitor (DRI). Group 3 received aliskiren 100 mg/kg/day ip for 4 weeks through gastric tube. Systolic blood pressure (SBP) was measured every week and its mean was recorded at the end of the study. Superoxide dismutase (SOD) enzyme in RBCs lysates, activities of catalase (CAT) and glutathione peroxidase enzymes and thiobarbituric acid reactive substance (TBARS), as a marker of lipid peroxidation, in hepatic homogenates were measured at the end of the study. DRI produced a marked reduction in mean SBP of hypertensive rats. It also significantly (p < 0.05) increased the activities of measured anti-oxidant enzymes while it significantly (p < 0.05) reduced TBARS in liver homogenates. These results indicated that renin possesses an oxidative effect in the liver in hypertensive rats. Aliskiren, in addition to its powerful anti-hypertensive effect, it could induce a great anti-oxidant effect in liver homogenates of DOCA salt-hypertensive rats.

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Section: Discussionsupporting

confidence: 82%

“…Dose of aliskiren was used according to Rashikh et al [7]. At the end of the study, each rat was anesthetized with urethane [1 g/kg], dissected and the livers were removed for anti-oxidant enzymes and TBARS measurement of their homogenates.…”

Section: Animal Protocolsmentioning

confidence: 99%

Aliskiren Augments the Activities of Anti-Oxidant Enzymes in Liver Homogenates of DOCA Salt-Induced Hypertensive Rats

Kamal¹

2014

AER

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“…The findings which are supportive of this hypothesis were found in a study which was done in relation to aliskiren. 41 Another parameter which showed oxidative stress in our study was the MDA. Our results showed that the MDA increased in I/R, and the increased MDA was decreased by aliskiren treatment.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study

et al. 2014

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(2015) Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study, Renal Failure, 37:2,[343][344][345][346][347][348][349][350][351][352][353][354] Purpose: To determine the protective effect of aliskiren on ischemia-reperfusion (I/R) injury in a rat renal (I/R) model. Methods: Rats were randomly divided into five groups: sham control group; sham control with aliskiren pretreatment; I/R group and I/R with two doses of aliskiren pretreatment. Rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Aliskiren (50 and 100 mg/kg) was administered orally by gavage 24 and 1 h prior to ischemia. After 24 h reperfusion, kidney samples were taken for the determination of malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione (GSH) activity and histological evaluation. The level of serum creatinine (SCR) and blood urea nitrogen (BUN), renin and angiotensin II (AT-2) was measured in serum samples. Results: Kidneys from I/R groups showed significant increase in MDA level and significant decrease in GSH, and SOD activity. IL-1b, iNOS and NFkB gene expression significantly increased in the I/R groups in the rat kidney tissue. Aliskiren treatment showed a significant down-regulatory effect on IL-1b, iNOS and NFkB mRNA expression. Compared with the sham group, SCR and BUN, renin and AT-2 were significantly increased in the I/R rats, accompanied by histopathological damage to the kidney. Conclusion: Pretreatment with aliskiren ameliorated I/R-induced renal injury through decreasing nitric oxide and AT-2 levels and by the reduction of injury induced by I/R injury and ameliorated renal histopathological molecular and biochemical changes.

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“…However, studies have suggested that angiotensin-converting enzyme (Wallace) inhibitor and angiotensin receptor blocker exert a protective role towards ADR-induced cardiotoxicity (Arozal et al 2010;Nakamae et al 2005). A new drug of renin angiotensin system (RAS) inhibitors (aliskiren (AL)) is a direct inhibitor of the renin enzyme (Rashikh et al 2012) and is reported to be cardioprotective against acute ADR-induced toxicity in heart (Rashikh et al 2013b) and kidney . In other words, the blockade of the renin activity by aliskiren might be a promising approach in the treatment of ADR-induced toxicity (Rashikh et al 2013a).…”

Section: Introductionmentioning

confidence: 99%

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

et al. 2014

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Adriamycin (ADR) increases the production of reactive oxygen species (ROS), which diminishes mitochondrial function. Angiotensin-II stimulates mitochondrial ROS generation. The aim of the study was to examine whether angiotensin converting enzyme (ACE) or renin inhibitors protect against ADR-induced mitochondrial function impairment. Rats were divided into five groups as control, ADR, co-treatment ADR with captopril, co-treatment ADR with aliskiren, co-treatment ADR with both captopril and aliskiren. Left ventricular function and blood pressures were assessed at the end of treatment period. Mitochondrial membrane potential (MMP) and ATP levels were determined. ADR treatment decreased the left ventricular pressure and increased the left ventricular end-diastolic pressure. ADR decreased MMP and ATP levels in myocyte mitochondria due to increasing oxidative stress. ADR decreased MMP and ATP levels due to increased oxidative stress in the heart. Inhibitors of ACE and renin caused the elevation of the decreased of MMP and ATP levels. The pathologic changes in electrocardiogram, blood pressure and left ventricular function were decreased by inhibition of Ang-II production. We concluded that inhibitors of angiotensin II are effective against ADR cardiotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.

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Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine model of cardiomyopathy

Cited by 29 publications

References 40 publications

Aliskiren Augments the Activities of Anti-Oxidant Enzymes in Liver Homogenates of DOCA Salt-Induced Hypertensive Rats

Aliskiren Augments the Activities of Anti-Oxidant Enzymes in Liver Homogenates of DOCA Salt-Induced Hypertensive Rats

Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

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