Abstract
•Doxorubicin cardiotoxicity is related to oxidative stress and inflammation of cardiac tissue.•Cannabidiol has antioxidant and anti-inflammatory activities.•Cannabidiol treatment ameliorated doxorubicin cardiotoxicity in rats via its antioxidant and anti-inflammatory effects.
The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg−1 i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg−1. Cannabidiol treatment (5mgkg−1/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.