Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity
Introduction
Doxorubicin is an anthracycline anticancer antibiotic commonly used for treatment of hematological malignancies and solid tumors. Despite the broad therapeutic effectiveness, the clinical use of doxorubicin is often limited because of its dose-dependent cardiotoxic adverse effects which frequently lead to congestive heart failure (Singal and Iliskovic, 1998, Minotti et al., 2004). Oxidative stress and inflammation play an important role in the pathogenesis of doxorubicin cardiotoxicity; indeed, several antioxidants and anti-inflammatory agents were proved effective in protecting against cardiac tissue damage induced by doxorubicin (Andreadou et al., 2007, Jiang et al., 2008, Ammar et al., 2011, Xin et al., 2011).
Cannabidiol is the major non-psychoactive cannabinoid component derived from the plant Cannabis sativa. It possesses powerful antioxidant and anti-inflammatory activities, although the exact mechanisms of action of cannabidiol remain obscure. In contrast to the other cannabinoids, cannabidiol is known to have a very low affinity for the cannabinoid CB1 and CB2 receptors. The antioxidant and anti-inflammatory activities of cannabidiol may be due to its direct action or mediated through a new cannabinoid, non-CB1 and non-CB2, receptor (Begg et al., 2005, De Petrocellis and Di Marzo, 2010). Cannabidiol may also exert its beneficial effects by inhibiting adenosine uptake and activating transient receptor potential vanilloid-1 (Bisogno et al., 2001, Carrier et al., 2006). Previous reports showed that cannabidiol may have therapeutic utility in a number of conditions involving inflammation and oxidative stress, including diabetes mellitus, rheumatoid arthritis, neurodegenerative disorders and ischemia/reperfusion tissue injury (Blake et al., 2006, Durst et al., 2007, Iuvone et al., 2009, Rajesh et al., 2010). However, to the best of our knowledge, the protective effect of cannabidiol against doxorubicin cardiotoxicity was not yet investigated.
Hence, we have conducted the present study to evaluate the potential cardioprotective effect of cannabidiol in rats which received doxorubicin, and to investigate the possible mechanisms underlying this protective effect.
Section snippets
Animals
Male Sprague-Dawley rats, weighing 250 ± 10 g were obtained from the Animal House, College of Medicine, King Faisal University. The animals were kept at standard housing facilities (24 ± 1 °C, 45 ± 5% humidity and 12 h light/dark cycle). They were supplied with standard laboratory chow and water ad libitum, and left to acclimatize for 1 week before the experiments. The experimental protocol was approved by the Ethical Committee, Deanship of Scientific Research, King Faisal University (approval number:
Effects of cannabidiol on the measured biochemical parameters
Significant increases of serum CK-MB and troponin T, and cardiac tissue levels of MDA, TNF-α, and NO, associated with a significant reduction in cardiac GSH resulted from doxorubicin administration as compared to the control values (p < 0.05). Cannabidiol treatment significantly attenuated the elevations of serum CK-MB and troponin T, and suppressed lipid peroxidation, reduced the elevations of TNF-α and NO, and prevented the depletion of GSH in cardiac tissue as compared to the doxorubicin group
Discussion
The present study revealed that cannabidiol treatment for four weeks provided a significant protective effect against doxorubicin-induced cardiotoxicity in rats. Also, the present results, in accordance with previous studies, showed that oxidative stress, depletion of antioxidant defenses and increased production of inflammatory mediators are implicated in the pathogenesis of doxorubicin cardiotoxicity (Andreadou et al., 2007, Jiang et al., 2008, Ammar et al., 2011, Xin et al., 2011). In
Conflict of interest statement
The authors declare that there is no conflict to disclose.
Acknowledgments
Special thanks to the Deanship of Scientific Research, King Faisal University for continuous encouragement and support. Also, special thanks to Dr Mohamed A. Morsy for his valuable advices.
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