Effect of poly(ADP-ribose) polymerase inhibition on outer medullary hypoxic damage.
Poly(ADP-ribose) polymerase (PARP) activation after free-radical-induced DNA damage depletes cellular energy stores and participates in ischemia-reflow injury. We studied the potential protective effect of the water-soluble PARP inhibitor 3-aminobenzamide (3-AB) in a rat model of acute renal failure (ARF) from combined administration of radiocontrast, indomethacin and N(omega)-nitro-L-arginine methyl ester. Kidney function at 24 h was better preserved in rats treated with 3-AB as compared to control animals. However, the extent of tubular hypoxic damage was not significantly mitigated. It is concluded that PARP inhibition may attenuate renal dysfunction in this model of ARF with medullary hypoxic tubular injury even while the extent of tubular necrosis is not significantly altered. Further studies of this dyssynchrony of structure and function may provide important insights into the sequence of events that promotes renal failure after medullary injury.
Darmon
David
D
Renal Unit, Bikur Holim Hospital, Jerusalem, Israel.
Goldfarb
Marina
M
Shina
Ahuva
A
Rosen
Seymour
S
Heyman
Samuel N
SN
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007213:Indomethacin; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009336:Necrosis; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D001549:Benzamides; D003287:Contrast Media; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin