Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats.
Ischemia and reperfusion injury (IRI) is a crucial contributor to the development of renal fibrosis. Ozone has been proposed as a novel medical therapy for various conditions, including organ IRI. The aim of this study was to investigate whether ozone oxidative preconditioning (OzoneOP) has a beneficial effect in preventing the development of renal fibrosis following IRI. Sprague Dawley rats were subjected to 45 min of ischemia followed by 8 weeks of reperfusion. Prior to surgery, rats in the OzoneOP group were treated with ozone and those in the IRI and Sham groups were untreated. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. To assess tissue fibrosis, Masson's trichrome staining was performed. Immunohistochemistry was also performed to determine the localization of α-smooth muscle actin (α-SMA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to analyze the expression of transforming growth factor (TGF)-β1, α-SMA and Smad7. The levels of BUN and Cr did not significantly differ between groups. Rats pretreated with ozone showed markedly less interstitial fibrosis than untreated rats following IRI. In addition, immunohistochemistry revealed that α-SMA expression was attenuated in the OzoneOP group compared with the IRI group. RT-qPCR and western blot analysis showed that OzoneOP inhibited the IRI-induced increases in α-SMA and TGF-β1 expression levels, and that the IRI-induced reduction in the expression of Smad7 was inhibited in the OzoneOP group. The results indicate that OzoneOP has beneficial effects on ischemic renal fibrosis. OzoneOP may exert its protective effects by a mechanism involving modulation of the TGF-β1/Smad7 pathway.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Lei
L
Wang
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Hui
H
Chen
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Xiu-Heng
XH
Liu
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Zhi-Yuan
ZY
Chen
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Xiao-Dong
XD
Weng
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Tao
T
Qiu
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Lin
L
Liu
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Heng-Cheng
HC
Zhu
ischemia and reperfusion injury; ozone oxidative preconditioning; renal fibrosis