Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo.

Abstract

Hydrogen peroxide (H202) contributes to renal cellular injury.a-Keto acids nonenzymatically reduce H202 to water while un- dergoing decarboxylation at the 1-carbon (1-C) position.We examined, in vitro and in vivo, the protective role of sodium pyruvate in H202-induced renal injury.Pyruvate effectively scavenged H202 in vitro, and suppressed H202-induced renal lipid peroxidation.Injury to LLC-PK1 cells induced by hydro- gen peroxide was attenuated by pyruvate to an extent compara- ble to that seen with catalase.Studies utilizing 1[-14Cjpyruvate further demonstrated 1-C decarboxylation concurrent with cy- toprotection by pyruvate from H202-induced injury.Pyruvate was also protective in vivo.Infusion of pyruvate before and during the intrarenal infusion of H202 attenuated H202-induced proteinuria.Systemic administration of pyruvate was also protective in the glycerol model of acute renal failure, a model also characterized by increased generation of H202.These findings indicate that pyruvate, a ubiquitous a-keto acid, scavenges H202 and protects renal tissue in vitro and in vivo from H202-mediated injury.These data suggest a potential therapeutic role for pyruvate in diseases in which increased generation of H202 is incriminated in renal damage.(J.Clin.Invest.1991.88:1886-1893.)Key words: a-keto acids * kidney * oxidant stress * proteinuria * scavengerIntroduction Numerous studies have established an important role for reac- tive oxygen species in mediating injury in a variety ofmodels of renal disease (1, 2).In particular, hydrogen peroxide (H202), a diffusible reactive oxygen metabolite formed by either enzyme- catalyzed or spontaneous dismutation of superoxide anion, is implicated in the pathogenesis of tissue damage in glycerol-in- duced injury (3), ischemia-reperfusion injury (4, 5), gentamicin nephropathy (6), and neutrophil-dependent glomerular injury (2, 7, 8).H202 is toxic when administered to the intact kidney (9) or the isolated perfused kidney (10), and inflicts cellular