Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo.
Hydrogen peroxide (H2O2) contributes to renal cellular injury. alpha-Keto acids nonenzymatically reduce H2O2 to water while undergoing decarboxylation at the 1-carbon (1-C) position. We examined, in vitro and in vivo, the protective role of sodium pyruvate in H2O2-induced renal injury. Pyruvate effectively scavenged H2O2 in vitro, and suppressed H2O2-induced renal lipid peroxidation. Injury to LLC-PK1 cells induced by hydrogen peroxide was attenuated by pyruvate to an extent comparable to that seen with catalase. Studies utilizing [1-14C]pyruvate further demonstrated 1-C decarboxylation concurrent with cytoprotection by pyruvate from H2O2-induced injury. Pyruvate was also protective in vivo. Infusion of pyruvate before and during the intrarenal infusion of H2O2 attenuated H2O2-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 H2O2. These findings indicate that pyruvate, a ubiquitous alpha-keto acid, scavenges H2O2 and protects renal tissue in vitro and in vivo from H2O2-mediated injury. These data suggest a potential therapeutic role for pyruvate in diseases in which increased generation of H2O2 is incriminated in renal damage.
Salahudeen
A K
AK
Department of Medicine, University of Minnesota, Minneapolis 55455.
Clark
E C
EC
Nath
K A
KA
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005990:Glycerol; D006861:Hydrogen Peroxide / Q000633:toxicity*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D011773:Pyruvates; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; D005990:Glycerol