title: Sildenafil activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in a rat model of renal ischemia/reperfusion injury.
abstract: OBJECTIVE
  To study the possible renoprotective effect of sildenafil against renal ischemia/reperfusion (I/R) injury and its effect on the expression of some antioxidant, antiapoptotic gene and proinflammatory cytokine genes in rat model of renal I/R injury.
  
  
  METHODS
  One hundred and twenty male Sprague Dawley rats were subdivided into three equal groups: sham (underwent right nephrectomy without ischemia), control (underwent right nephrectomy and left ischemia for 45 min) and study [as control with 1 mg/kg sildenafil (per oral) 60 min before anesthesia]. Serum creatinine and BUN were measured at the baseline and the study endpoints (2, 24, 48 h and 7 days), and the left kidney was harvested at study endpoints for histopathological examination as well as for assessment of the expression of antioxidant genes (Nrf-2, HO-1 and NQO-1), antiapoptotic gene (Bcl-2) and inflammatory cytokines, e.g., TNF-a, IL-1β and ICAM-1.
  
  
  RESULTS
  I/R caused significant increase in serum creatinine, BUN, histopathological damage score (p < 0.001) and significant reduction in antioxidant genes (nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) with significant increase in TNF-a, IL-1β and ICAM-1 genes in kidney tissues. Pretreatment with sildenafil caused significant attenuation of serum creatinine and BUN as well as significant increase in the expression of antioxidant genes and Bcl-2 genes with significant reduction in the expression of proinflammatory cytokine genes (p value < 0.001).
  
  
  CONCLUSIONS
  The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1β and ICAM-1).
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Zahran
authors.affiliation: Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. zizomenna28@yahoo.com.
authors.forename: Abdelaziz M
authors.initials: AM
authors.lastname: Hussein
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Nashwa
authors.initials: N
authors.lastname: Barakat
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Amira
authors.initials: A
authors.lastname: Awadalla
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Shery
authors.initials: S
authors.lastname: Khater
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Harraz
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Shokeir
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D009392:Nephrectomy; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D000068677:Sildenafil Citrate / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D058986:Phosphodiesterase 5 Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine; D000068677:Sildenafil Citrate; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat
keywords: Bcl-2; HO-1; Ischemia/reperfusion; Kidney; NQO-1; Nrf2; Sildenafil