Research the protective effect of melatonine on Dox- induced cardiotoxicity in isolated perfused rat heart

Doxorubicin is a highly effective cancer chemotherapeutic agent and its clinical use is limited by its serious cardiotoxicity. Although the exact mechanism of its cardiotoxicity is stil unknown, oxidative damage is suggested to play a major role in Doxorubicin- induced cardiotoxicity. Recent studies have showed that many antioxidant agents have protective effects on cardiotoxicity of anthracyclines like Doxorubicin.Melatonine is a pineal secretory hormone which is shown in many studies as a free radical scavenger and antioxidant. Melatonin has been found useful in many pathology related with oxidative damage.In this study we aimed to research the protective effect of melatonine on Dox- induced cardiotoxicity in isolated perfused rat heart. Male wistar albino rats were divided into four groups: 1.group: control (1 ml steril saline i.p), 2.group: Doxorubicin (one dose, 10mg/kg (i.p) ), 3.group: Dox ( one dose, 10 mg/kg (i.p)) + Melatonine ( for 7 days once a day 10 mg/kg (i.p)), 4.group: melatonine (for 7 days once a day 10 mg/kg (i.p) ). After 7 days, the hearts were isolated by sternotomy in all groups. After aorta isolated and cannulated by Langendorff system hearts were perfused with constant flow of Krebs- Henseleit solution (aired with 95% O2 + 5% CO2 ) and maintened at 37 0C.Coronary perfusion pressure and -via a latex balloon inserted in the left ventricle -left ventricular developed pressure (LVDP) and heart rate by electrodes were recorded on a computer. Also LV( dP/dt)max and LV( dP/dt)min which shows max and min pressures during systole and diastole per time were recorded.During the experiments it was observed that in Dox group coronary perfusion pressure and LV( dP/dt)min were significantly increased, heart rate, LVDP and LV(dP/dt)max were significantly reduced versus control group. In contrary in Dox + melatonine group coronary perfusion pressure and LV( dP/dt)min were significantly decreased, heart rate, LVDP and LV(dP/dt)max were significantly increased versus Dox group.It is concluded that melatonine has protective effects on doxorubicin induced cardiotoxicity with altered heart contractility and hemodynamics.