title: Ozone therapy could attenuate tubulointerstitial injury in adenine-induced CKD rats by mediating Nrf2 and NF-κB.
abstract: OBJECTIVE
  This study aims to determine the effects of ozone therapy on restoring impaired Nrf2 activation to ameliorate chronic tubulointerstitial injury in rats with adenine-induced CKD.
  
  
  METHODS
  Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and chronic tubulointerstitial injury. Ozone therapy was administered by rectal insufflation. After 4 weeks, serum and kidney samples were collected and analyzed. Renal function and systemic electrolyte level were detected. Pathological changes in kidney were assessed by hematoxylin-eosin staining and Masson trichrome staining. Nrf2 activation was detected by immunohistochemistry and Western blot analyses. The levels of SOD, CAT, GSH, PCO, and MDA were detected in the kidney. Immunohistochemistry, Western blot, and real-time PCR analyses were performed to evaluate the activation of the nuclear factor kappa B (NF-κB) P65 pathway and inflammation infiltration in the tubulointerstitium of the rats.
  
  
  RESULTS
  Ozone therapy improved severe renal insufficiency and tubulointerstitial morphology injury as well as restored Nrf2 activation and inhibited the NF-κB pathway in rats with adenine-induced CKD. Ozone therapy also up-regulated anti-oxidation enzymes (SOD, CAT, and GSH) and down-regulated oxidation products (PCO and MDA), as well as inflammatory cytokines (IL-1β, IL-6, TNF-α, and ICAM-1) in the kidney.
  
  
  CONCLUSIONS
  These findings indicated that ozone therapy could attenuate tubulointerstitial injury in rats with adenine-induced CKD by mediating Nrf2 and NF-κB.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Xiuheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Weng
keywords: Adenine; Nuclear factor erythroid-2-related factor 2; Ozone therpy; Rat; Tubuleinterstitial injury