اسم المؤلف:
ايهاب اياد احمد
اسم المشرف:
علي اسماعيل عبد الله محمد
خالد جمعة خليل
المستخلص:
اجريت الدراسة الحالية لتقييم التاثيرالعلاجي لاستخدام الروزوفاستاتين والتلمسارتان في التقليل من سمية القلب المحدثة من عقار الدوكسوروبسين في الجرذان المختبريةباستخدام الطرق الكيميائية الحيوية والنسيجية ومقارنة تاثير الاستخدام المزدوج بفعالية استخدام كل م | Background : Doxorubicin, an anthracycline antibiotic is a powerful antineoplastic drug, but its therapeutic usefulness is limited by its cardiotoxicity. Aim of the study : The present study investigated the influence of pretreatment with rosuvastatin and telmisartan alone or in combination in different doses on doxorubicin induced acute cardiotoxicity in rats using biochemical and histological approaches. Materials and methods : The animals were divided into eight groups of 5 animals each. The first group received no drug(s) po but a single dose of distilled water (7.5 ml/kg, ip) on day eight, which serves as the control group. The second group received no drug(s) po but a single dose of doxorubicin (15 mg/kg, ip) on day eight, and serves as doxorubicin only received group. The third and sixth group received rosuvastatin (2 , 10) mg/kg/day respectively for nine successive days, and on day eight, one hour after drug administration, a single dose of doxorubicin (15 mg/kg, ip) was given. The fourth and seventh group received telmisartan (2 , 4) mg/kg/day respectively for nine successive days, and on day eight, one hour after drug administration, a single dose of doxorubicin (15 mg/kg, ip) was given. The fifth and eighth group received both drugs, where the fifth group received both of rosuvastatin (2 mg/kg, po) and telmisartan (2 mg/kg, po), 1 hour apart, daily for nine successive days, and on day eight, one hour after drug administration, a single dose of doxorubicin (15 mg/kg, ip) was given. While the eighth group received both of rosuvastatin (10 mg/kg, po) and telmisartan (4 mg/kg, po), 1 hour apart, daily for nine successive days, and on day eight, one hour after drug administration, a single dose of doxorubicin (15 mg/kg, ip) was given.At day ten of the study, blood samples were taken for biochemical analysis, then animals were sacrificed and hearts were taken for histopathological observations. Results : Rats treated with doxorubicin showed cardiotoxicity as evidenced by significant elevation of serum cardiac troponin (CTn - I) level, lactate dehydrogenase (LDH) activity, serum malondialdehyde (MDA) level, and interluekine 17 (IL - 17) level associated with important histopathological alterations while pre - treatment with rosuvastatin and telmisartan elicited a significant decrease in the activities of all markers measured in comparison with doxorubicin treated group with pronounced resolution of Dox induced cardiac histological changes to a milder picture.Conclusion : These results suggest pretreatment with rosuvastatin and telmisartan alone or in combination provide a significant protective effect against acute - doxorubicin induced cardiotoxicity in rats represented by biochemical markers and histological approaches.
