Mp73-15 Protective Effect of Ethyl Pyruvate on Oxidative Renal Cell Injury: Implication in Prevention of Renal Ischemia/Reperfusion Injury

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology III1 Apr 2017MP73-15 PROTECTIVE EFFECT OF ETHYL PYRUVATE ON OXIDATIVE RENAL CELL INJURY: IMPLICATION IN PREVENTION OF RENAL ISCHEMIA/REPERFUSION INJURY Jonathan Bloom, Mark Ferretti, Matthew Chaimowitz, Muhammad Choudhury, Majid Eshghi, and Sensuke Konno Jonathan BloomJonathan Bloom More articles by this author , Mark FerrettiMark Ferretti More articles by this author , Matthew ChaimowitzMatthew Chaimowitz More articles by this author , Muhammad ChoudhuryMuhammad Choudhury More articles by this author , Majid EshghiMajid Eshghi More articles by this author , and Sensuke KonnoSensuke Konno More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3360AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Various renal cell injuries, including renal ischemia/reperfusion injury (RIRI), have been shown to be primarily attributed to oxidative stress. Particularly, to protect the kidneys from RIRI, the perioperative interventions have been routinely employed but the outcomes remain elusive. To improve the efficacy of renoprotection, certain antioxidant such as ethyl pyruvate (EPy) may more effectively prevent RIRI as its safety or beneficial and therapeutic effects have been well documented. Accordingly, we investigated the protective effects of EPy and mannitol (Mann), one of perioperative agents often used, on renal cells against oxidative stress in vitro. METHODS Oxidative stress was exerted by hydrogen peroxide (H2O2) on the renal proximal tubular MDCK cells. Severity of oxidative stress was determined by malondialdehyde (MDA) assay and protective effects of EPy and Mann against H2O2 were assessed by cell viability test. To explore the cytotoxic mechanism of H2O2, the status of glycolytic parameters, cell cycle, and metabolic signaling pathways as well as induction of apoptosis was also examined. RESULTS H2O2 (500 µM) increased the MDA level by ~3.5 times of controls, but PE (1 mM) nearly completely reduced it to the basal level. Although cell viability was reduced to merely 10% by H2O2 in 24 h, EPy yet maintained >90% cell viability. Two glycolytic parameters, hexokinase activity and ATP level, declined to ~45% and ~30% (compared to controls) by H2O2, respectively. This decline significantly (80-90%) went up with EPy. H2O2 also induced a G1 cell cycle arrest and the modulations of metabolic signaling regulators such as AMP-activated protein kinase (AMPK), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). EPy utterly reversed a cell cycle arrest and prevented those modulations. Analysis of two key apoptosis regulators, bcl-2 and Bax, further indicated induction of apoptosis by H2O2, which was yet fully prevented with EPy. Unlike EPy, Mann had little effects on any H2O2-induced adverse cellular effects. CONCLUSIONS Oxidative stress exerted by H2O2 can cause cell injury and death in MDCK cells. It involves the cell viability reduction, the glycolysis inhibition, a cell cycle arrest, the modulations of metabolic signaling pathways, and ultimately induction of apoptosis. However, all these adverse effects through oxidative stress were effectively and nearly completely prevented or reversed with EPy, not with Mann. Therefore, EPy should be considered as a more effective prophylactic and perioperative renoprotective agent (compared with Mann) against oxidative renal cell injury including RIRI. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e969 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jonathan Bloom More articles by this author Mark Ferretti More articles by this author Matthew Chaimowitz More articles by this author Muhammad Choudhury More articles by this author Majid Eshghi More articles by this author Sensuke Konno More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...