title: Activation of Nrf2 by ischemic preconditioning and sulforaphane in renal ischemia/reperfusion injury: a comparative experimental study.
abstract: Objectives of the study were to investigate impact of ischemic preconditioning (Ipre) and sulforaphane (SFN) and combination of them on nuclear factor 2 erythroid related factor 2 (Nrf2) gene and its dependent genes, heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase1 (NQO-1) and inflammatory cytokines TNF-alpha, IL1beta, and intercellular adhesion molecule-1 (ICAM1) and caspase-3 in renal ischemia/reperfusion (I/R) injury. Ninety male Sprague Dawely rats were classified into 5 groups (each consists of 18 rats): sham, control, Ipre, sulforaphane and Sulfo+Ipre. Each group was subdivided into 3 subgroups each containing 6 rats according to time of harvesting kidney and taking blood samples; 24 h, 48 h, and 7 days subgroups. Renal functions including serum creatinine, BUN were measured at basal conditions and by the end of experiment. Expression of Nrf2, HO-1, NQO-1, TNF-alpha, IL-1beta, and ICAM-1 was measured by real time PCR in kidney tissues by the end of experiment. Also, immunohistochemical localization of caspase-3 and chemical assay of malondialdehyde (MDA), GSH and SOD activity were measured in kidney tissues. Both Ipre and SFN improved kidney functions, enhanced the expression of Nrf2, HO-1, and NQO-1, attenuated the expression of inflammatory (TNF-alpha, IL-1, and ICAM-1) and apoptotic (caspase-3) markers. However, the effect of sulforaphane was more powerful than Ipre. Also, a combination of them caused more improvement in antioxidant genes expression and more attenuation in inflammatory genes but not caspase-3 than each one did separately. Sulforaphane showed more powerful effect in renoprotection against I/R injury than Ipre as well as there might be a synergism between them at the molecular but not at the function level.
authors.affiliation: Urology and Nephrology Center, Mansoura University and Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. zizomenna28@yahoo.com; menhag@mans.edu.eg.
authors.forename: A A
authors.initials: AA
authors.lastname: Shokeir
authors.forename: N
authors.initials: N
authors.lastname: Barakat
authors.forename: A M
authors.initials: AM
authors.lastname: Hussein
authors.forename: A
authors.initials: A
authors.lastname: Awadalla
authors.forename: A M
authors.initials: AM
authors.lastname: Harraz
authors.forename: S
authors.initials: S
authors.lastname: Khater
authors.forename: K
authors.initials: K
authors.lastname: Hemmaid
authors.forename: A I
authors.initials: AI
authors.lastname: Kamal
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D000818:Animals; D003131:Combined Modality Therapy; D016207:Cytokines / Q000276:immunology; D019194:Ischemic Preconditioning / Q000379:methods*; D017879:Isothiocyanates / Q000008:administration & dosage*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000276:immunology*; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D013454:Sulfoxides; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013454:Sulfoxides; C016766:sulforaphane