Drug Design, Development and Therapy (May 2018)
Ozone oxidative postconditioning inhibits oxidative stress and apoptosis in renal ischemia and reperfusion injury through inhibition of MAPK signaling pathway
Abstract
Lei Wang, Zhiyuan Chen, Yang Liu, Yang Du, Xiuheng Liu Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China Background: Ozone has been used as a curative agent for a variety of different diseases for over 150 years. In our previous study, we found that ozone oxidative preconditioning could alleviate renal damage induced by ischemia and reperfusion injury (I/R). Although this method had obvious protective effects in the reduction of I/R, its clinical application remains limited because this treatment must be commenced prior to the ischemic period, which is not practical in the clinic. Purpose: In the present study, we investigated whether ozone oxidative postconditioning (OzoneOP) could attenuate renal I/R in vivo and in vitro, as well as the mechanisms underlying the effects of this treatment. Methods: Sprague Dawley rats were subjected to right renal ischemia for 45 min and reperfusion for 24 h, or to sham operation with the left kidney removed, both with and without OzoneOP. In addition, normal rat kidney tubular epithelial cells (NRK-52E) were chosen to create a hypoxia–reoxygenation (H/R) model of 3 h hypoxia and 24 h reoxygenation processes, both with or without OzoneOP and mitogen-activated protein kinase (MAPK) inhibitors. Results: Our results showed that OzoneOP significantly reversed apoptosis and the abnormal superoxide dismutase and malondialdehyde levels induced by I/R or H/R. OzoneOP also inhibited activation of the MAPK pathways both in vivo and in vitro, which resulted in significant protection against apoptosis and oxidative stress. Conclusion: Our current data provide evidence that OzoneOP might serve as a potential therapy for renal I/R. Keywords: ozone, ischemia and reperfusion, MAPK
