title: Treatment with aliskiren ameliorates tacrolimus-induced nephrotoxicity in rats.
abstract: BACKGROUND
  Tacrolimus is frequently used as immunosuppressive agent in organ transplantation but its clinical use is limited due to its marked nephrotoxicity.
  
  
  METHODS
  Male Wistar albino rats weighing 150-200 g (10-12 weeks old) were used. Animals were divided into four groups. Group 1 served as control group and received normal saline, group 2 served as toxic group and received 2 mg/kg tacrolimus i.p., group 3 served as treatment group and received 2 mg/kg tacrolimus i.p. followed by 2 mg/kg aliskiren orally and group 4 served as drug per se group and received 2 mg/kg aliskiren orally. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically.
  
  
  RESULTS
  Treatment with aliskiren decreased the tacrolimus-induced changes in biochemical markers of nephrotoxicity such as blood urea nitrogen and creatinine. Aliskiren also attenuated the effects of tacrolimus on oxidative stress parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that aliskiren attenuated tacrolimus-induced renal damage.
  
  
  CONCLUSIONS
  These results suggest that aliskiren has protective effects against tacrolimus-induced nephrotoxicity; implying that renin inhibitor may counteract nephrotic syndrome associated with immunosuppressant use.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of 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, Kingdom of Saudi Arabia fimam@ksu.edu.sa.
authors.forename: Faisal
authors.initials: F
authors.lastname: Imam
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of 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, Kingdom of Saudi Arabia.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia.
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shahrah
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia.
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Korashy
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Al-Hosaini
authors.affiliation: Department of Zoology, College of Science, King Saud University, Kingdom of Saudi Arabia.
authors.forename: Mukhtar
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Kingdom of Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Bahashwar
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D016559:Tacrolimus / Q000009:adverse effects*
chemical_list: D000577:Amides; D005650:Fumarates; C446481:aliskiren; D002374:Catalase; D005978:Glutathione; D016559:Tacrolimus
keywords: Aliskiren; nephrotoxicity; renin inhibitor; tacrolimus