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Olmesartan attenuates tacrolimus-induced biochemical and ultrastructural changes in rat kidney tissue

Naif O Al-Harbi1, Faisal Imam1, Mohammed M Al-Harbi1

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Biomed Research International
|July 3, 2014
PubMed

Insights

Olmesartan, an angiotensin receptor blocker, protects against tacrolimus-induced nephrotoxicity in rats. This study shows olmesartan reduces kidney damage markers and improves renal histology, suggesting a role for the renin-angiotensin system in tacrolimus side effects.

Area of Science:

  • Nephrology
  • Pharmacology
  • Immunosuppression

Background:

  • Tacrolimus is a vital immunosuppressant in organ transplantation.
  • Nephrotoxicity is a significant limitation of tacrolimus therapy.
  • The renin-angiotensin system (RAS) may contribute to tacrolimus-induced kidney damage.

Purpose of the Study:

  • To investigate the protective effect of olmesartan against tacrolimus-induced nephrotoxicity in a rat model.
  • To explore the potential role of the renin-angiotensin system in tacrolimus nephrotoxicity.

Main Methods:

  • Rats were divided into control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups.
  • Nephrotoxicity was assessed using biochemical markers (BUN, creatinine, MDA, GSH, catalase).
  • Renal tissue was examined histopathologically and ultrastructurally.

Main Results:

  • Tacrolimus significantly increased BUN and creatinine levels, and MDA, while decreasing GSH and catalase activity.
  • Olmesartan treatment reversed these biochemical changes induced by tacrolimus.
  • Histopathological and ultrastructural analyses confirmed that olmesartan prevented renal tubule, mitochondria, and podocyte damage.

Conclusions:

  • Olmesartan demonstrates significant protective effects against tacrolimus-induced nephrotoxicity in rats.
  • These findings suggest that the renin-angiotensin system plays a role in the development of tacrolimus nephrotoxicity.
  • Olmesartan may be a potential therapeutic agent to mitigate tacrolimus-related kidney damage.

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