Inhibition of poly(ADP-ribose) polymerase attenuates ischemic renal injuryin rats

The enzyme, poly( ADP-ribose) polymerase (PARP), effects repair of DNA afte r ischemia-reperfusion (I/R) injury to cells in nerve and muscle tissue. Ho wever, its activation in severely damaged cells can lead to ATP depletion a nd death. We show that PARP expression is enhanced in damaged renal proxima l tubules beginning at 6-12 h after I/R injury. Intraperitoneal administrat ion of PARP inhibitors, benzamide or 3-amino benzamide, after I/R injury ac celerates the recovery of normal renal function, as assessed by monitoring the levels of plasma creatinine and blood urea nitrogen during 6 days posti schemia. PARP inhibition leads to increased cell proliferation at 1 day pos tinjury as assessed by proliferating cell nuclear antigen and improves the histopathological appearance of kidneys examined at 7 days postinjury. Furt hermore, inhibition of PARP increases levels of ATP measured at 24 h postis chemia compared with those in vehicle-treated animals. Our data indicate th at PARP activation is a part of the cascade of molecular events that occurs after I/R injury in the kidney. Although caution is advised, transient inh ibition of PARP postischemia may constitute a novel therapy for acute renal failure.