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.
journal_name
Cardiovasc Toxicoljournal_title
Cardiovascular toxicologyauthors
Imam F,Al-Harbi NO,Al-Harbia MM,Korashy HM,Ansari MA,Sayed-Ahmed MM,Nagi MN,Iqbal M,Khalid Anwer M,Kazmi I,Afzal M,Bahashwan Sdoi
10.1007/s12012-015-9356-5subject
Has Abstractpub_date
2017-01-01 00:00:00pages
58-66issue
1eissn
1530-7905issn
1559-0259pii
10.1007/s12012-015-9356-5journal_volume
17pub_type
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