Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren

• Published in: Toxicology mechanisms and methods Vol. 24; no. 9; pp. 697 - 702
• Main Authors: Al-Harbi, Naif O, Imam, Faisal, Nadeem, Ahmed, Al-Harbi, Mohammed M, Iqbal, Muzaffar, Rahman, Shakilur, Al-Hosaini, Khalid A, Bahashwan, Saleh
• Format: Journal Article
• Language: English
• Published: 01.12.2014
• ISSN: 1537-6516; 1537-6524
• DOI: 10.3109/15376516.2014.970679

Context: 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 waste evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity. Materials and methods: Male Wistar albino rats weighing 200-250g (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 14d), group 3 received OLM (2 mg/kg, p.o. for 28d) + TAC and group 4 received ALK (50 mg/kg, p.o. for 28d) + 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. Discussion and conclusion: 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.