Impact of Ivabradine on Reactive Nitrogen and Oxygen Radicals in Doxorubicin Induced Acute Cardiotoxicity in Mice

Boshra, Vivian and Shalaby, Amany (2015) Impact of Ivabradine on Reactive Nitrogen and Oxygen Radicals in Doxorubicin Induced Acute Cardiotoxicity in Mice. British Journal of Medicine and Medical Research, 6 (12). pp. 1166-1176. ISSN 22310614

[thumbnail of Shalaby6122014BJMMR10764.pdf] Text
Shalaby6122014BJMMR10764.pdf - Published Version

Download (526kB)

Abstract

Doxorubicin (DOX) has been used in variety of human malignancies for decades. Despite its efficacy in cancer, clinical usage is limited because of its cardiotoxicity, which has been associated with oxidative stress. The possible protective mechanisms of ivabradine, a selective inhibitor of the I(f) channel, against acute doxorubicin cardiotoxicity were investigated in mice. Cardiac toxicity was induced by a single intraperitoneal injection of doxorubicin (15 mg/kg). Ivabradine treatment (10 mg/kg/day, orally) was started 5 days before doxorubicin administration. Ivabradine significantly reduced the elevated heart rate and the serum cardiac enzymes resulted from DOX administration. Also, ivabradine reversed DOX-induced deficits in the antioxidant defense mechanisms, decreased lipid peroxidation in cardiac tissue and attenuated the production of nitric oxide levels by induced nitric oxide synthase enzyme. In addition, DOX-induced cardiac tissue damage observed by histopathological examination was markedly ameliorated with ivabradine. In conclusion, the beneficial effects of ivabradine against DOX induced cardiotoxicity are mediated by the reduction of heart rate with inhibition of oxidative stress and nitric oxide detrimental effects.

Item Type: Article
Subjects: AP Academic Press > Medical Science
Depositing User: Unnamed user with email support@apacademicpress.com
Date Deposited: 15 Jun 2023 07:09
Last Modified: 21 Sep 2024 03:54
URI: http://info.openarchivespress.com/id/eprint/1442

Actions (login required)

View Item
View Item