Ozone therapy could attenuate tubulointerstitial injury in adenine-induced CKD rats by mediating Nrf۲ and NF-κB

Objective(s): This study aims to determine the effects of ozone therapy on restoring impaired Nrf۲ activation to ameliorate chronic tubulointerstitial injury in rats with adenine-induced CKD. Materials and Methods: Sprague–Dawley rats were fed with ۰.۷۵% adenine-containing diet to induce CKD and chronic tubulointerstitial injury. Ozone therapy was administered by rectal insufflation. After ۴ 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. Nrf۲ 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) P۶۵ 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 Nrf۲ 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-۱β, IL-۶, TNF-α, and ICAM-۱) in the kidney. Conclusion:These findings indicated that ozone therapy could attenuate tubulointerstitial injury in rats with adenine-induced CKD by mediating Nrf۲ and NF-κB.

Keywords:

Adenine , Nuclear factor erythroid-۲-related factor ۲ , Ozone therpy , Rat , Tubuleinterstitial injury