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See comment in PubMed Commons belowBiomed Res Int. 2014;2014:607246. doi: 10.1155/2014/607246. Epub 2014 May 28.
Olmesartan attenuates tacrolimus-induced biochemical and ultrastructural changes in rat kidney tissue.
- 1
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
- 2
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
- 3
- El-Ghad International College for Health Science, Riyadh 11451, Saudi Arabia.
- 4
- Al-Haya Medical Co., Riyadh 11411, Saudi Arabia.
Abstract
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.
Figure 1
Effect of olmesartan on tacrolimus-induced changes in BUN and creatinine levels in serum of different experimental groups. The data are expressed as mean ± SEM (n = 6). *P < 0.05 versus control group; **P < 0.05 versus toxic group. ANOVA followed by the Tukey-Kramer multiple comparison tests.
Biomed Res Int. 2014;2014:607246.
Figure 2
Effect of olmesartan on tacrolimus-induced changes in total protein and albumin levels in serum of different experimental groups. The data are expressed as mean ± SEM (n = 6). *P < 0.05 versus control group; **P < 0.05 versus toxic group. ANOVA followed by Tukey-Kramer multiple comparison tests.
Biomed Res Int. 2014;2014:607246.
Figure 3
Effect of olmesartan on tacrolimus-induced changes in glutathione and lipid peroxidation in kidney of different experimental groups. The data are expressed as mean ± SEM (n = 6). *P < 0.05 versus control group; **P < 0.05 versus toxic group. ANOVA followed by the Tukey-Kramer multiple comparison tests.
Biomed Res Int. 2014;2014:607246.
Figure 4
Effect of olmesartan on tacrolimus-induced changes in catalase activity in kidney of different experimental groups. The data are expressed as mean ± SEM (n = 6). *P < 0.05 versus control group; **P < 0.05 versus toxic group. ANOVA followed by the Tukey-Kramer multiple comparison tests.
Biomed Res Int. 2014;2014:607246.
Figure 5
Effect of olmesartan on tacrolimus-induced changes histopathology in kidney of different experimental groups. (a) Control group; (b) toxic group; (c) treatment group; and (d) drug per se group (n = 6 per group). Magnification at 40x.
Biomed Res Int. 2014;2014:607246.
Figure 6
Effect of olmesartan on tacrolimus-induced ultrastructural changes in kidney of different experimental groups. (a) Control group; (b) toxic group; (c) treatment group, and (d) drug per se group (n = 6 per group). Podocyte foot process and mitochondrial integrity were assessed using transmission electron microscopy (magnification = ×10000).
Biomed Res Int. 2014;2014:607246.
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