Effects Of Melatonin On Adriamycin Induced Myocardial Injury In Rats

Background: In chemotherapy for malignant process,the adverse reactions of anti-cancer drugs limit the application of anti-cancer drugs.Adriamycin(ADM) is an anthracycline antibiotic, a commonly used drug of the cancer treatment drugs, but the cumulative dose-related cardiac toxicity is a major constraint on the long-term application of high-dose ADM.ADM induced cardiac toxicity most because of it caused the formation of oxygen free radicals, but the heart can not effectively trans-shipment oxygen free radicals ,in myocardial mitochondria there is a unique enzyme, the enzyme so that ADM reduced to semiquinone, cause severe oxidative stress.Therefore, to find an effective anti-oxidants reduce the adriamycin on myocardial injury,it provide a new possibilitie for clinical prevention and treatment on adriamycin induced myocardial injury.Objective:To study effects of melatonin on adriamycin induced myocardial injury in rats.Methods:Forty adult SD rats were randomized into five groups(n=8):control group, ADM group, MLT+ADM group, VitE+ADM group, MLT+VitE+ADM groups.After 30 days,left ventricular collagen volume fraction,the activity of myocardial superoxide dismutase,the concentration of malondialdehyde, the Bax/Bcl-2 of protein expression were assayed. The pathomorphology changes cardiomyocytes were detected optical microscope. Results:By Ridit analysis pathological injury scale can be seen by ADM group, VitE+ADM group, MLT+ADM group, MLT+VitE+ADM group in turn reduce the extent of myocardial injury. Compared with the control group of rats,the concentration of MDA in ADM group rats were significantly higher, the activity of SOD were significant lower, myocardial cells'Bax gene protein expression were higher and Bcl-2 gene protein expression were lower. To MLT, VitE treatment can significantly reduce the myocardial tissue'concentration of MDA, and significantly enhance the activity of SOD,the expression of bcl-2 increased significantly while the expression of bax decreased significantly.Masson staining showed increased left ventricular collagen, myocardial interstitial fibrosis obvious in ADM group. ADM group collagen volume fraction (CVF) was higher than the control group(P<0.01); and VitE+ADM group CVF lower than the ADM group (P<0.01), MLT+ADM group CVF lower than VitE+ADM group(P<0.01), MLT+VitE+ADM group CVF lower than MLT+ADM group(P<0.01). Compared the two kinds of antioxidants, MLT in the rat myocardium of the antioxidant capacity is higher than VitE, the combined effect of antioxidant capacity is more than the two separate applications.Conclusion:MLT and VitE can enhance myocardial antioxidant capacity and protection myocardial,and the antioxidant capacity of MLT is higher than VitE, the combined effect of antioxidant capacity is significantly,the mechanisms are possibly due to MLT can prevent free radical damage from various sectors and have synergies.