Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren
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 ind...
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Published in | Toxicology mechanisms and methods Vol. 24; no. 9; pp. 697 - 702 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.12.2014
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Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 1537-6516 1537-6524 |
DOI: | 10.3109/15376516.2014.970679 |