title: Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia. Electronic address: amrfouad65@yahoo.com.
authors.forename: Amr A
authors.initials: AA
authors.lastname: Fouad
authors.affiliation: Department of Pediatrics, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
authors.forename: Waleed H
authors.initials: WH
authors.lastname: Albuali
authors.affiliation: Department of Surgery, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
authors.forename: Abdulruhman S
authors.initials: AS
authors.lastname: Al-Mulhim
authors.affiliation: Department of Biomedical Sciences, Pathology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
authors.forename: Iyad
authors.initials: I
authors.lastname: Jresat
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004317:Doxorubicin; D053222:Fas Ligand Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020107:Troponin T / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D018836:Inflammation Mediators; D016328:NF-kappa B; D020011:Protective Agents; D020107:Troponin T; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; D009569:Nitric Oxide; D008315:Malondialdehyde; D004317:Doxorubicin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D052279:Creatine Kinase, MB Form; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D012643:Selenium; D015032:Zinc; D002118:Calcium
keywords: Cannabidiol; Doxorubicin cardiotoxicity; Inflammation; Oxidative stress; Rats