title: Mechanisms underlying the protective effect of eugenol in rats with acute doxorubicin cardiotoxicity.
abstract: The protective effect of eugenol and its possible mechanisms were investigated in rats with acute doxorubicin cardiotoxicity. Cardiac toxicity was induced by a single intraperitoneal injection of doxorubicin (20 mg/kg). Eugenol treatment (5 mg/kg/day, orally) was started 2 days before doxorubicin administration and continued for five consecutive days. Eugenol significantly reduced the elevated serum creatine kinase and lactate dehydrogenase levels, and restored the electrocardiographic disturbances resulted from doxorubicin administration. Also, eugenol reversed doxorubicin-induced deficits in the antioxidant defense mechanisms, decreased lipid peroxidation and attenuated the elevations in cytosolic Ca(2+) and nitric oxide levels in cardiac tissue. In addition, doxorubicin-induced cardiac tissue damage observed by histopathological examination was markedly ameliorated with eugenol. Immunohistochemical analysis revealed that eugenol prevented the doxorubicin-induced activation of caspase-3 in cardiomyocytes. The cardioprotective effect afforded by eugenol was not significantly inhibited by prior administration of capsazepine, the transient potential vanilloid receptor-1 antagonist. It was concluded that eugenol, through its antioxidant activity and its ability to reduce cardiac Ca(2+) accumulation and nitric oxide levels, is a potential candidate to protect against acute doxorubicin cardiotoxicity, a major and dose-limiting clinical problem.
authors.affiliation: Department of Biomedical Sciences, Division of Pharmacology, College of Medicine, Al-Ahsa, King Faisal University, Saudi Arabia. amrfouad65@yahoo.com
authors.forename: Amr A
authors.initials: AA
authors.lastname: Fouad
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Yacoubi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000627:therapeutic use; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D054715:Cardiotoxins / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005054:Eugenol / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002316:Cardiotonic Agents; D054715:Cardiotoxins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D009569:Nitric Oxide; D005054:Eugenol; D004317:Doxorubicin; C505410:Casp3 protein, rat; D053148:Caspase 3; C071423:capsazepine; D002211:Capsaicin