title: Olmesartan attenuates tacrolimus-induced biochemical and ultrastructural changes in rat kidney tissue.
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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Faisal
authors.initials: F
authors.lastname: Imam
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Muzaffar
authors.identifier: 0000-0001-5821-5600
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
authors.affiliation: El-Ghad International College for Health Science, Riyadh 11451, Saudi Arabia.
authors.forename: Ali D
authors.initials: AD
authors.lastname: Alabidy
authors.affiliation: Al-Haya Medical Co., Riyadh 11411, Saudi Arabia.
authors.forename: Ali F
authors.initials: AF
authors.lastname: Almukhallafi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D065095:Calcineurin Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000009:adverse effects* / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D065095:Calcineurin Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D016559:Tacrolimus