title: Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren.
abstract: BACKGROUND
  Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin-angiotensin aldosterone system.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity.
  
  
  METHODS
  Male Wistar albino rats weighing 200-250 g (10-12 weeks old) were used in this study. Animals were divided into four groups. Group 1 received normal saline, group 2 received TAC (2 mg/kg, intraperitoneally for 14 d), group 3 received OLM (2 mg/kg, p.o. for 28 d) + TAC and group 4 received ALK (50 mg/kg, p.o. for 28 d) + TAC. TAC-induced cardiotoxicity was assessed biochemically and histopathologically.
  
  
  RESULTS
  Treatment with OLM or ALK decreased the TAC-induced changes in biochemical markers of cardiotoxicity such as serum aspartate transaminase, creatine kinase and lactate dehydrogenase. OLM or ALK also attenuated the effects of TAC on oxidant-antioxidant parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that OLM or ALK also attenuated TAC-induced cardiotoxicity.
  
  
  CONCLUSIONS
  These results suggest that OLM as well as ALK has protective effects against TAC-induced cardiotoxicity; implying that angiotensin receptor blocker or renin inhibitor, respectively, may counteract cardiotoxicity associated with immunosuppressant use.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University , Riyadh , KSA .
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.forename: Faisal
authors.initials: F
authors.lastname: Imam
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Al-Harbi
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Iqbal
authors.forename: Shakilur
authors.initials: S
authors.lastname: Rahman
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Al-Hosaini
authors.forename: Saleh
authors.initials: S
authors.lastname: Bahashwan
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D005650:Fumarates / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000633:toxicity*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000577:Amides; D005650:Fumarates; D007093:Imidazoles; D007166:Immunosuppressive Agents; D013777:Tetrazoles; C446481:aliskiren; C437965:olmesartan; D016559:Tacrolimus
keywords: Angiotensin receptor blocker; aliskiren; cardiotoxicity; olmesartan; renin angiotensin aldosterone system; renin inhibitor; tacrolimus