title: Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf-2-dependent genes by ischaemic pre-conditioning and post-conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury.
abstract: OBJECTIVE
  To investigate the impact of ischaemic pre-conditioning (Ipre) and post-conditioning (Ipost) on expression of nuclear factor erythroid 2-related factor 2 (Nrf2) gene and its dependent genes, haem oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1); inflammatory cytokines TNF-α, IL1β and ICAM-1; and apoptotic markers such as caspase-3 in renal ischaemia/reperfusion (I/R) injury.
  
  
  METHODS
  One hundred and fifty male Sprague Dawley rats were classified into five groups (each consisted of 30 rats): sham, control (I/R), Ipre + I/R, Ipre without I/R and Ipost + I/R. Serum creatinine and blood urea nitrogen (BUN) were measured at 2, 24 and 48 h after ischaemia. In kidney tissues, mRNA of Nrf2, HO-1, NQO-1, TNF-α, IL-1β and ICAM-1 and immunohistochemical expression of Nrf2 and caspase-3 were assessed.
  
  
  RESULTS
  Serum creatinine and BUN improved significantly in Pre + I/R group; however, they did not show any significant improvement in Post + I/R group. Also, Ipre-I/R group showed non-significant change in serum creatinine and BUN. The expression of Nrf2, HO-1 and NQO-1 is increased significantly in Pre + I/R and Pre - I/R groups, while the enhancement in Post + I/R group was non-significant. Moreover, the expression of proinflammatory cytokines (TNF-α, IL-1 and ICAM-1) and apoptotic (caspase-3) markers showed high significant attenuation in Pre + I/R group, but slight significant attenuation in Pre + I/R group.
  
  
  CONCLUSIONS
  The renoprotective action of Ipre might include early activation and enhanced expression of Nrf2 gene and its dependent antioxidant genes, HO-1 and NOQ1, as endogenous adaptive renoprotective genes, as well as reduction in TNF-α, IL-1β, ICAM-1 and caspase-3.
authors.affiliation: Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: A A
authors.initials: AA
authors.lastname: Shokeir
authors.forename: A M
authors.initials: AM
authors.lastname: Hussein
authors.forename: N
authors.initials: N
authors.lastname: Barakat
authors.forename: A
authors.initials: A
authors.lastname: Abdelaziz
authors.forename: M
authors.initials: M
authors.lastname: Elgarba
authors.forename: A
authors.initials: A
authors.lastname: Awadalla
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000222:Adaptation, Physiological; D000818:Animals; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007150:Immunohistochemistry; D057775:Ischemic Postconditioning / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat
keywords: HO‐1; NQO‐1; Nrf2; apoptosis; cytokines; ischaemia/reperfusion; post‐conditioning; pre‐conditioning