Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats

Wang,Lei; Chen,Hui; Liu,Xiu-Heng; Chen,Zhi-Yuan; Weng,Xiao-Dong; Qiu,Tao; Liu,Lin; Zhu,Heng-Cheng

doi:10.3892/etm.2014.2004

December-2014 Volume 8 Issue 6

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December-2014 Volume 8 Issue 6

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Article

Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats

Authors:
- Lei Wang
- Hui Chen
- Xiu-Heng Liu
- Zhi-Yuan Chen
- Xiao-Dong Weng
- Tao Qiu
- Lin Liu
- Heng-Cheng Zhu
View Affiliations / Copyright

Affiliations: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Pages: 1764-1768
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Published online on: October 6, 2014

https://doi.org/10.3892/etm.2014.2004
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Abstract

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.

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1	Yun Y, Duan WG, Chen P, et al: Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats. Transplant Proc. 41:3597–3602. 2009. View Article : Google Scholar
2	Barri YM, Sanchez EQ, Jennings LW, et al: Acute kidney injury following liver transplantation: definition and outcome. Liver Transpl. 15:475–483. 2009. View Article : Google Scholar : PubMed/NCBI
3	Schrier RW, Wang W, Poole B and Mitra A: Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest. 114:5–14. 2004. View Article : Google Scholar : PubMed/NCBI
4	Nankivell BJ, Borrows RJ, Fung CL, et al: The natural history of chronic allograft nephropathy. N Engl J Med. 349:2326–2333. 2003. View Article : Google Scholar : PubMed/NCBI
5	Cook HT: The origin of renal fibroblasts and progression of kidney disease. Am J Pathol. 176:22–24. 2010. View Article : Google Scholar : PubMed/NCBI
6	Li R, Chung AC, Dong Y, et al: The microRNA miR-433 promotes renal fibrosis by amplifying the TGF-β/Smad3-Azin1 pathway. Kidney Int. 84:1129–1244. 2013.PubMed/NCBI
7	Ni H, Chen J, Pan M, et al: FTY720 prevents progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease. J Mol Histol. 44:693–703. 2013. View Article : Google Scholar : PubMed/NCBI
8	Zeisberg M, Maeshima Y, Mosterman B and Kalluri R: Renal fibrosis. Extracellular matrix microenvironment regulates migratory behavior of activated tubular epithelial cells. Am J Pathol. 160:2001–2008. 2002.
9	Zhang X, Yang J, Li Y and Liu Y: Both Sp1 and Smad participate in mediating TGF-beta1-induced HGF receptor expression in renal epithelial cells. Am J Physiol Renal Physiol. 288:F16–F26. 2005. View Article : Google Scholar : PubMed/NCBI
10	Nakao A, Afrakhte M, Morén A, et al: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 389:631–635. 1997. View Article : Google Scholar : PubMed/NCBI
11	Ren ZP, Sun LP, Xia YC and Tong QX: Effect of the protease inhibitor MG132 on the transforming growth factor-β/Smad signaling pathway in HSC-T6 cells. J Huazhong Univ Sci Technolog Med Sci. 33:501–504. 2013.
12	Ajamieh HH, Menendez S, Martinez-Sanchez G, et al: Effects of ozone oxidative preconditioning on nitric oxide generation and cellular redox balance in a rat model of hepatic ischaemia-reperfusion. Liver Int. 24:55–62. 2004. View Article : Google Scholar : PubMed/NCBI
13	Ajamieh HH, Berlanga J, Merino N, et al: Role of protein synthesis in the protection conferred by ozone-oxidative-preconditioning in hepatic ischaemia/reperfusion. Transpl Int. 18:604–612. 2005. View Article : Google Scholar
14	Chen H, Xing B, Liu X, et al: Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury. Eur J Pharmacol. 581:306–314. 2008. View Article : Google Scholar : PubMed/NCBI
15	Martinez-Sanchez G, Al-Dalain SM, Menendez S, et al: Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol. 523:151–161. 2005. View Article : Google Scholar : PubMed/NCBI
16	León Fernández OS, Pantoja M, Díaz Soto MT, et al: Ozone oxidative post-conditioning reduces oxidative protein damage in patients with disc hernia. Neurol Res. 34:59–67. 2012.PubMed/NCBI
17	Leon OS, Menendez S, Merino N, et al: Ozone oxidative preconditioning: a protection against cellular damage by free radicals. Mediators Inflamm. 7:289–294. 1998. View Article : Google Scholar : PubMed/NCBI
18	Feitoza CQ, Goncalves GM, Semedo P, et al: Inhibition of COX 1 and 2 prior to renal ischemia/reperfusion injury decreases the development of fibrosis. Mol Med. 14:724–730. 2008. View Article : Google Scholar : PubMed/NCBI
19	Weng X, Shen H, Kuang Y, et al: Ischemic postconditioning inhibits the renal fibrosis induced by ischemia-reperfusion injury in rats. Urology. 80:481–484. 2012. View Article : Google Scholar : PubMed/NCBI
20	Liu Y: Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 69:213–217. 2006. View Article : Google Scholar : PubMed/NCBI
21	Border WA and Noble NA: TGF-beta in kidney fibrosis: a target for gene therapy. Kidney Int. 51:1388–1396. 1997. View Article : Google Scholar : PubMed/NCBI
22	Kellenberger T, Krag S, Danielsen CC, et al: Differential effects of Smad3 targeting in a murine model of chronic kidney disease. Physiol Rep Dec. 1:e001812013.PubMed/NCBI
23	Wang Y1, Zhang Z, Shen H, Lu Y, Li H, Ren X and Wu G: TGF-beta1/Smad7 signaling stimulates renal tubulointerstitial fibrosis induced by AAI. J Recept Signal Transduct Res. 28:413–428. 2008. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats

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