title: Effects of Angiotensin II Receptor Blockade on Soluble Klotho and Oxidative Stress in Calcineurin Inhibitor Nephrotoxicity in Rats.
abstract: BACKGROUND
  Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress.
  
  
  METHODS
  Thirty-two Sprague-Dawley rats were divided into 4 groups to receive 1 mL/kg/d of olive oil as control; 30 mg/kg/d of cyclosporine; 30 mg/kg/d of cyclosporine and 50 mg/kg/d of valsartan; and 50 mg/kg/d of valsartan. After the 6 weeks of administration period, serum levels of klotho and 8-hydroxydeoxyguanosine were measured using an enzyme-linked immunosorbent assay. Serum malondialdehyde level was measured spectrophotometrically.
  
  
  RESULTS
  The mean serum level of klotho was significantly lower in the cyclosporine group compared with control and valsartan groups. Klotho level in the valsartan group was significantly higher than those in the other groups. The cyclosporine group was detected to have significantly higher serum 8-hydroxydeoxyguanosine and malondialdehyde levels compared with the other study groups. The levels of klotho were negatively correlated with 8-hydroxydeoxyguanosine and malondialdehyde levels.
  
  
  CONCLUSIONS
  Administration of valsartan may lead to attenuation of the nephrotoxic side effect of cyclosporine via enhancing klotho and decreasing oxidative stress levels.
authors.forename: Sina
authors.initials: S
authors.lastname: Raeisi
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ghorbaniamir@hotmail.com.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghorbanihaghjo
authors.forename: Hassan
authors.initials: H
authors.lastname: Argani
authors.forename: Siavoush
authors.initials: S
authors.lastname: Dastmalchi
authors.forename: Babollah
authors.initials: B
authors.lastname: Ghasemi
authors.forename: Teimour
authors.initials: T
authors.lastname: Ghazizadeh
authors.forename: Nadereh
authors.initials: N
authors.lastname: Rashtchizadeh
authors.forename: Mahboob
authors.initials: M
authors.lastname: Nemati
authors.forename: Mehran
authors.initials: M
authors.lastname: Mesgari Abbasi
authors.forename: Nasrin
authors.initials: N
authors.lastname: Bargahi
authors.forename: Ali
authors.initials: A
authors.lastname: Mota
authors.forename: Amir Mansour
authors.initials: AM
authors.lastname: Vatankhah
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D065095:Calcineurin Inhibitors / Q000633:toxicity*; D016572:Cyclosporine / Q000633:toxicity*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005966:Glucuronidase / Q000097:blood / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D000090265:Klotho Proteins; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D065095:Calcineurin Inhibitors; D008315:Malondialdehyde; D000068756:Valsartan; D016572:Cyclosporine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005966:Glucuronidase; D000090265:Klotho Proteins; D003849:Deoxyguanosine