اسم المؤلف:
محـمد عبد العزيز محـمد
اسم المشرف:
حيدر مطير خليل القريشي
خالد جمعة خليل
المستخلص:
Doxorubicin is a member of anthracycline antibiotic that widely used in the treatment of different types of cancer such as hematological malignances, solid tumors, and different organ tumors, doxorubicin is very efficient in the treatment of cancer. But the use of doxorubicin is limited by the side effect of doxorubicin on the same organ, the most important organ that affected by doxorubicin is the heart, the toxicity of doxorubicin in the heart, the use of doxorubicin due to the cardiotoxicity that induced by doxorubicin will lead to cardiomyopathy and in the final result of these cardiotoxicity lead to congestive heart failure that occurred secondary to the cardiotoxicity may appear after long period of termination of treatment by doxorubicin.ObjectivesThe aim of the present study its investigate the possible modulation effect of drugs (verapamil, cyclosporine, labetalol) on the cardiotoxicity that induced by doxorubicin drug. Animals and methods forty Dwale - Spargue male rats where enrolled in this study, the animals divided into groups, (5) rats in each group and assigned as I,II,III,IV,V,VI,VII,VIII.Group I : received physiological saline (5ml/kg), orally, daily for ten days and served as the control.Group II : received a single dose of doxorubicin (15mg/kg), intraperitoneal and was sacrificed after 48 hours which served as doxorubicin group.Group III : received verapamil (5mg/kg), orally daily for ten days and on day eight, one hour after drug administration, a single dose of doxorubicin (15mg/kg), intraperitoneal were given.Group IV : received cyclosporine (0.5mg/kg), orally daily for ten days, and on day eight, one hour after drug administration, a single dose of doxorubicin (15mg/kg, intraperitoneal) was given.Group V : received cyclosporine (1mg/kg), orally daily for ten days ,and on day eight ,one hour after drug administration a single dose of doxorubicin (15mg/kg),intraperitoneal was given. Group VI : received both of verapamil (5mg/kg,orally) and cyclosporine (0.5mg/kg,orally) one hour apart, daily for ten days ,and on day eight, one hour after drug administration ,a single dose of doxorubicin (15mg/kg), intraperitoneal was given.Group VII : received labetalol (0.5mg/kg), orally daily for ten days, and on day eight, one hour after drug administration, a single dose of doxorubicin (15mg/kg, intraperitoneal) was given. Group VIII : received labetalol (1mg/kg, orally),daily for ten days ,and on day eight ,one hour after drug administration ,a single dose of doxorubicin (15mg/kg), intraperitoneal was given.Serum MDA, LDH, Troponin I, and interleukine - 17. Were measured and histopathological changes also viewed?ResultsThe results in this study showed an increase in the cardiac biomarkers in the doxorubicin group compared to the control group, the cardiac biomarkers that measured are LDH, MDA, Troponin I, interleukine - 17. Also the results showed histopathalogical changes in cardiac tissue in doxorubicin group as compared to the control group, also the results showed the pre - treatment with verapamil, cyclosporine low dose, cyclosporine high dose, combination of verapamil and cyclosporine low dose, labetalol low dose, labetalol high dose showed decreasing in the cardiac biomarkers MDA, LDH, Troponin I, interleukine - 17 to a significant amount compared to the doxorubicin group, also showed histopathlogical improvement in cardiac tissue. Conclusions Doxorubicin drug used as antineoplastic agent will produce a toxic effect on the cardiac tissue, this toxic effect will limit the use of doxorubicin, cyclosporine, labetalol and verapamil produced differential effects and protection from Doxorubicin induced cardio toxicity via amelioration of cardiac biomarkers and histopathological changes
