Mechanisms underlying the protective effect of eugenol in rats with acute doxorubicin cardiotoxicity |
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Authors: | Amr A Fouad Mohamed T Yacoubi |
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Institution: | (1) Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;(2) Department of Pharmacology and Toxicology, Faculty of Medicine, University of Maastricht, 6200 MD Maastricht, The Netherlands;(3) Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;(4) ICaR-VU, VU University Medical Center, 1081 HV Amsterdam, The Netherlands |
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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 Ca2+ 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 Ca2+ accumulation and nitric oxide levels, is a potential candidate to protect against acute doxorubicin cardiotoxicity, a major
and dose-limiting clinical problem. |
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