Çocuk Sağlığı ve Hastalıkları Dergisi 2004 , Vol 47 , Num 4
Effect of melatonin on doxorubicininduced experimental cardiotoxicity.
Funda Demir1, Figen Narin2, Hülya Akgün3, Kazım Üzüm4, Recep Saraymen5, Ali Baykan1, Esat Köklü1
Erciyes Üniversitesi Tıp Fakültesi 1Pediatri Uzmanı, 2Biyokimya Yardımcı Doçenti, 3Patoloji Öğretim Görevlisi, 4Pediatri Profesörü, 5Biyokimya Uzmanı Demir F, Narin F, Akgün H, Üzüm K, Saraymen R, Baykan A, Köklü E (Departments of Pediatrics, Biochemistry and Pathology, Erciyes University Faculty of Medicine, Kayseri, Turkey). Effect of melatonin on doxorubicininduced experimental cardiotoxicity. Çocuk Sağlığı ve Hastalıkları Dergisi 2004; 47: 260-268.

Doxorubicin, a widely used antineoplastic agent in clinical practice, has a serious side effect, cardiotoxicity. Due to the risk of life-threatening cardiotoxicity which limits doxorubicin’s therapeutic potential, diagnosis and prevention of doxorubicin-induced cardiotoxicity become essential. Free radicals, lipid peroxidation and antioxidant enzymes are suggested to be mainly involved in doxorubicin-induced cardiotoxicity pathogenesis. The aim of this study was evaluation of the pathogenesis of doxorubicin-induced cardiotoxicity and the effect of melatonin. The study was designed with three groups: in the first group (n=10 young rabbits) doxorubicin was administered in six equal intraperitoneal injections over a period of two weeks (cumulative dose 15 mm/ kg). The second group (n=7 young rabbits) who received melatonin (10 mg/ kg/day intraperitoneally) 24 hours before intraperitoneal doxorubicin, and it was continued seven days after the last dose of doxorubicin. The third group was the control group (n=7). We measured myocardial and plasma glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA) activities and myocardial nitric oxide (NO) activity in our rabbit model. Serum troponin I (Tn I) and creatine kinase (CK-MB) values were tested for diagnostic value of cardiotoxicity. Our results suggested that doxorubicin formed severe cardiotoxicity in young rabbits with 15 mg/kg cumulative doses with markedly decreased myocardial GSH-Px and increased MDA and NO values. Melatonin reduced doxorubicin-induced cardiotoxicity by increasing myocardial GSH-Px and SOD activities. Although serum Tn I and CK-MB levels had diagnostic values, any change in plasma GSH-Px, SOD and MDA activities was determined in assessing doxorubicin-induced cardiotoxicity. In conclusion, decreased antioxidant enzyme levels, increased free radicals and lipid peroxidation play a major role in the pathogenesis of doxorubicin-induced cardiotoxicity, and melatonin is an effective antioxidant in reducing doxorubicininduced cardiotoxicity. Anahtar Kelimeler : doksorubisin, nitrik oksit, glutatyon peroksidaz, malondialdehit, melatonin,doxorubicin, nitric oxide, glutathione peroxidase, malondialdehyte, melatonin.

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