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

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 ?-smooth muscle actin (?-SMA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to analyze the expression of transforming growth factor (TGF)-?1, ?-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 ?-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 ?-SMA and TGF-?1 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-?1/Smad7 pathway.

SUBMITTER: Wang L

PROVIDER: S-EPMC4218702 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Wang Lei L Chen Hui H Liu Xiu-Heng XH Chen Zhi-Yuan ZY Weng Xiao-Dong XD Qiu Tao T Liu Lin L Zhu Heng-Cheng HC

Experimental and therapeutic medicine 20141006 6

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 Oz ...[more]

PMID: 25371729

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Project description:BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

Dataset Information

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

Publications

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

Similar Datasets

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