Effects of NF-kappa B on doxorubicin induced myocardium injury and melatonin treatment in rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of NF-κB on cardiomyopathy induced by doxorubicin(Dox) in rats and the effect of melatonin(MT). METHODS Thirty male Sprague-Dawley rats were randomly divided into 3 groups normal control group; Dox model group; Dox+MT group. The content of nitric oxide (NO) and the activity of inducible nitric oxide synthase (iNOS) in cardiac tissues were examined by spectrophotography method; the activity of NF-κB in myocardial cell was observed by immunohistochemistry method; the apoptosis information of myocardial cell was detected by TUNEL method. RESULTS There was significant difference in activity of NF-κB between normal control and the Dox model group. MT could inhibit the activation of NF-κB(P＜0.05). There was significant difference in the content of NO and the activity of iNOS between normal control and Dox model group, MT could decrease content of NO and the activity of iNOS(P＜0.05); apoptotic rate in Dox model group was significantly increased compared with that in normal control group, MT could significantly decrease myocardial cell apoptosis (P＜0.05). CONCLUSION The activation of NF-κB plays an important role in cardiomyopathy induced by Dox, NF-κB seems to increase the activity of iNOS, and then significantly increase the content of NO in cardiac muscle; NF-κB possibly enhances myocardial cell apoptosis in cardiomyopathy induced by Dox. MT may inhibit the activation of NF-κB, and prevent excessive oxidative stress and suppress myocardial cell apoptosis, MT has protective effect against cardiomyopathy induced by Dox.