Rutin Attenuates Carfilzomib-Induced Cardiotoxicity Through Inhibition of NF-κB, Hypertrophic Gene Expression and Oxidative Stress View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-01

AUTHORS

Faisal Imam, Naif O. Al-Harbi, Mohammed M. Al-Harbia, Hesham M. Korashy, Mushtaq Ahmad Ansari, Mohamed M. Sayed-Ahmed, Mahmoud N. Nagi, Muzaffar Iqbal, Md. Khalid Anwer, Imran Kazmi, Muhammad Afzal, Saleh Bahashwan

ABSTRACT

Carfilzomib is a proteasome inhibitor, commonly used in multiple myeloma, but its clinical use may be limited due to cardiotoxicity. This study was aimed to evaluate the influence of rutin in carfilzomib-induced cardiotoxicity in rats. Wistar albino male rats weighing 200-250 g (approximately 10 weeks old) were taken for this study. Animals were divided into four groups of six animals each. Group 1 served as normal control (NC), received normal saline; group 2 animals received carfilzomib (dissolved in 1 % DMSO) alone; group 3 animals received rutin (20 mg/kg) + carfilzomib; and group 4 animals received rutin (40 mg/kg) + carfilzomib. Hematological changes, biochemical changes, oxidative stress, hypertrophic gene expression, apoptotic gene expression, NFκB and IκB-α protein expression and histopathological evaluation were done to confirm the finding of carfilzomib-induced cardiotoxicity. Treatment with rutin decreased the carfilzomib-induced changes in cardiac enzymes such as lactate dehydrogenase, creatine kinase (CK) and CK-MB. For the assessment of cardiotoxicity, we further evaluated cardiac hypertrophic gene and apoptotic gene expression such as α-MHC, β-MHC and BNP and NF-κB and p53 gene expression, respectively, using RT-PCR. Western blot analysis showed that rutin treatment prevented the activation of NF-κB by increasing the expression of IκB-α. Rutin also attenuated the effects of carfilzomib on oxidant-antioxidant including malondialdehyde and reduced glutathione. Histopathological study clearly confirmed that rutin attenuated carfilzomib-induced cardiotoxicity in rats. More... »

PAGES

58-66

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12012-015-9356-5

DOI

http://dx.doi.org/10.1007/s12012-015-9356-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021269597

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26707720


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