Protective Effect of RIVA Against Sunitinib-Induced Cardiotoxicity by Inhibiting Oxidative Stress-Mediated Inflammation: Probable Role of TGF-β and Smad Signaling

Imam, Faisal; Al-Harbi, Naif O.; Khan, Mohammad Rashid; Qamar, Wajhul; Alharbi, Metab; Alshamrani, Ali A.; Alhamami, Hussain N.; Alsaleh, Nasser B.; Alharbi, Khalid Saad

doi:10.1007/s12012-019-09551-8

Cited by 17 publications

(13 citation statements)

References 51 publications

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“…Moreover, a deleterious effect of SUN on the heart was emphasized by a drastic rise in serum CK-MB besides a significant inflammatory state, which concurred with the biochemical and histological features. The histological findings were manifested as fragmented cardiac muscle fibers with vacuolations and extensive separations along with excessive collagen depositions, in agreement with previous studies [ 5 , 27 , 42 ]. Hence, our results indicated that using SUN could be a promising model for studying the pathological mechanism of cardiac fibrosis and therapeutic interventions.…”

Section: Discussionsupporting

confidence: 92%

“…Secukinumab dose concentration was adapted according to previous studies [ 16 , 26 ]. The selected dose of SUN was chosen after our experimental trials to induce cardiotoxicity in rats and was adapted from Imam et al [ 27 ] ( Supplementary Figure S1 and Table S1 ). Docking study was performed to ensure the efficacy of using secukinumab (human monoclonal antibody) against rat IL-17A in this study ( Supplementary Figure S2 and Table S2 ).…”

Section: Methodsmentioning

confidence: 99%

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Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats

Mohamad

Asker

Shaheen

et al. 2023

Life

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Sunitinib has been associated with several cardiotoxic effects such as cardiac fibrosis. The present study was designed to explore the role of interleukin (IL)-17 in sunitinib-induced myocardial fibrosis (MF) in rats and whether its neutralization and/or administration of black garlic (BG), a form of fermented raw garlic (Allium sativum L.), could extenuate this adverse effect. Male Wistar albino rats received sunitinib (25 mg/kg three times a week, orally) and were co-treated with secukinumab (3 mg/kg, subcutaneously, three times total) and/or BG (300 mg/kg/day, orally) for four weeks. Administration of sunitinib induced significant increase in cardiac index, cardiac inflammatory markers, and cardiac dysfunction that were ameliorated by both secukinumab and BG, and to a preferable extent, with the combined treatment. Histological examination revealed disruption in the myocardial architecture and interstitial fibrosis in cardiac sections of the sunitinib group, which were reversed by both secukinumab and BG treatments. Both drugs and their co-administration restored normal cardiac functions, downregulated cardiac inflammatory cytokines, mainly IL-17 and NF-κB, along with increasing the MMP1/TIMP1 ratio. Additionally, they attenuated sunitinib-induced upregulation of the OPG/RANK/RANKL axis. These findings highlight another new mechanism through which sunitinib can induce interstitial MF. The current results propose that neutralizing IL-17 by secukinumab and/or supplementation with BG can be a promising therapeutic approach for ameliorating sunitinib-induced MF.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats

Mohamad

Asker

Shaheen

et al. 2023

Life

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“…Mitochondrial dysfunction and redox imbalance may contribute to pathological states known as "free radical diseases". in an animal model, sunitinib significantly decreased glutathione and glutathione reductase activity and increased malondialdehyde, an indicator of lipid peroxidation in cardiac tissues [11].…”

Section: Left Ventricular Systolic Dysfunctionmentioning

confidence: 91%

Cardiotoxicity of antiangiogenic drugs: causes and mechanisms

Tomaszewska¹,

Muzolf²,

Grabysa

et al. 2021

OncoReview

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Therapy with angiogenesis inhibitors is undoubtedly an advancement in cancer treatment; however, it is associated with a risk of developing cardiotoxicity, which most often manifests in myocardial contractile dysfunction or an increased risk of thromboembolic events. Heart failure is observed in 2–4% of patients treated with bevacizumab and in 3–8% of patients on antiangiogenic tyrosine kinase inhibitors. The proposed pathomechanisms underlying the impairment in systolic function during antiangiogenic drug treatment include mitochondrial dysfunction, a secondary reduction in cardiomyocyte ATP production and redox imbalance, which may contribute to pathological states known as “free radical diseases”. Additionally, therapy with angiogenesis inhibitors may also cause cardiac oxidative stress. The risk factors for cardiac complications include arterial hypertension, which is a known “class effect” of this class of drugs, as well as a number of other factors such as age, comorbidities, prior radiotherapy and baseline left ventricular ejection fraction. The cardiovascular diseases are still the first cause of death in the world. The more effective oncological treatment becomes, the more often comorbidities occur. This fact seems to demand interdisciplinary approach from investigators and practitioners. This article presents the current state of knowledge on the molecular mechanisms of cardiotoxicity of antiangiogenic drugs used in routine clinical practice.

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“…To cope with sunitinib-induced cardiotoxicity, RIVA blocks TGF-β and Smads signaling and inhibits oxidative stress-mediated inflammation. 81 In addition, TGF-β bound with synthesized short peptide polymers used for material surface modification can continuously release TGF-β and regulate material-induced inflammation, which would provide key functions for tissue regeneration and repair. 82 …”

Section: Relationships Between Bmp9 and Inflammation In Different Tis...mentioning

confidence: 99%

The potential regulatory role of BMP9 in inflammatory responses

2022

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Protective Effect of RIVA Against Sunitinib-Induced Cardiotoxicity by Inhibiting Oxidative Stress-Mediated Inflammation: Probable Role of TGF-β and Smad Signaling

Cited by 17 publications

References 51 publications

Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats

Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats

Cardiotoxicity of antiangiogenic drugs: causes and mechanisms

The potential regulatory role of BMP9 in inflammatory responses

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