title: Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response.
abstract: BACKGROUND
  The importance of doxorubicin (Dox), as a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy. It has been shown that free radicals are involved in acute doxorubicin-induced toxicity. The aim of this study was to determine the protective effect of vitamin E and telmisartan in acute doxorubicin induced cardiotoxicity.
  
  
  METHODS
  Thirty two male Sprague - Dawley rats were involved in this study and were randomly separated into 4 groups, eight rats in each group, one group received normal saline I.P as control and second group received doxorubicin 20 mg/kg I.P, the other two groups also received doxorubicin 20 mg/kg I.P as single dose after seven cumulative doses (for seven days) of vitamin E (100 mg/kg) and telmisartan (1 mg/kg) respectively. Immunofluorescent staining for monocytes infiltration and analyses of plasma by (ELISAs) for MCP-1and troponin I. Western immunoblotting assay for ICAM-1, while left ventricular function was analyzed by microcatheter, also estimated the level of oxidative stress parameters (MDA and Catalase) and cardiac enzymes activities (CK-MB and LDH) before starting drugs treatment and after treatment period by 48 hours.
  
  
  RESULTS
  The immunofluorescent staining showed that administration of vitamin E and telmisartan are attenuated of mononuclear cell infiltration; (p < 0.05 vs. Dox group), also reduced the level of chemokines MCP-1 and ICAM-1 expression compared with Dox group only, and there is marked reduction of myocardial troponin-I levels with improved LV function in vitamin E and telmisartan treated group. Doxorubicin treatment increased MDA, LDH, CK-MB levels significantly (P < 0.01), and were counteracted by administration of vitamin E and telmisartan, but did not significantly affect serum catalase activity.
  
  
  CONCLUSIONS
  Antioxidant effect (vitamin E and telmisartan) have been shown to decrease doxorubicininduced cardiotoxicity.
authors.affiliation: University of Colorado Denver, Department of Medicine and Surgery Aurora, Denver, CO 80045, USA.
authors.forename: Najah
authors.initials: N
authors.lastname: Hadi
authors.forename: Nasser Ghaly
authors.initials: NG
authors.lastname: Yousif
authors.forename: Fadhil G
authors.initials: FG
authors.lastname: Al-amran
authors.forename: Nadhem K
authors.initials: NK
authors.lastname: Huntei
authors.forename: Bassim I
authors.initials: BI
authors.lastname: Mohammad
authors.forename: Sadiq J
authors.initials: SJ
authors.lastname: Ali
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D015153:Blotting, Western; D006328:Cardiac Catheterization; D002374:Catalase / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood*; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation; D004317:Doxorubicin; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan; D013997:Time Factors; D019210:Troponin I / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D019210:Troponin I; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; D008315:Malondialdehyde; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D052279:Creatine Kinase, MB Form; D000077333:Telmisartan