tacrolimus and olmesartan

Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker) on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Tacrolimus significantly increased BUN and creatinine level. Treatment with olmesartan reversed tacrolimus-induced changes in the biochemical markers (BUN and creatinine) of nephrotoxicity. Tacrolimus significantly decreased GSH level and catalase activity while increasing MDA level. Olmesartan also attenuated the effects of tacrolimus on MDA, GSH, and catalase. In tacrolimus group histological examination showed marked changes in renal tubule, mitochondria, and podocyte processes. Histopathological and ultrastructural studies showed that treatment with olmesartan prevented tacrolimus-induced renal damage. These results suggest that olmesartan has protective effects on tacrolimus-induced nephrotoxicity, implying that RAS might be playing role in tacrolimus-induced nephrotoxicity.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Calcineurin Inhibitors; Imidazoles; Kidney Diseases; Kidney Tubules, Proximal; Male; Mitochondria; Podocytes; Rats; Rats, Wistar; Tacrolimus; Tetrazoles

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.. The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity.. 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.. 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.. 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.

Topics: Amides; Animals; Fumarates; Heart; Imidazoles; Immunosuppressive Agents; Male; Myocardium; Rats; Rats, Wistar; Tacrolimus; Tetrazoles