The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats

Author:

Munir Sania1,Hafeez Rizwan2,Younis Waqas34,Malik Muhammad Nasir Hayat3,Munir Muhammad Usman5,Manzoor Wajiha3,Razzaq Muryam Abdul3,Pessoa Luciane Barbosa6,Lopes Katiana Simões6,Lívero Francislaine Aparecida dos Reis7,Gasparotto Junior Arquimedes6ORCID

Affiliation:

1. The Faculty of Pharmacy, Superior University, Lahore 54000, Pakistan

2. Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore 54000, Pakistan

3. Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore 54590, Pakistan

4. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, 550 Ist Ave, New York, NY 10016, USA

5. Australian Institute for Bioengineering & Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia

6. Laboratory of Cardiovascular Pharmacology (LaFac), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79804-970, MS, Brazil

7. Laboratory of Cardiometabolic Pharmacology, Department of Pharmacology, Federal University of Parana, Curitiba 81530-900, PR, Brazil

Abstract

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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