Role of poly(ADP-ribose) polymerase activation in development of multiple organ failure in ischemia-reperfusion injury

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Purpose : We evaluated the cytoprotective effects of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) polymerase (PARP), in multiple organ failure in ischemia-reperfusion injury.Methods : Rats, administered either 3AB (3AB group) or saline (control group), were subjected to intestinal ischemia (90 minutes) and reperfusion. Sham group rats underwent simple laparotomy. 3AB improved the survival rate and tissue blood flow after intestinal ischemia-reperfusion.Results : Compared with sham group rats, intestinal and hepatic ATP levels in the control group and 3AB group were decreased after intestinal ischemia-reperfusion. The 3AB group, however, had significantly higher intracellular ATP levels in the intestine as well as liver than the control group. Moreover, histological evaluation revealed that the 3AB group had less intestinal mucosal damage than the control group. Control rats showed positive staining of the residual basal intestinal mucosa by immunohistological staining of TUNEL, 8-hydroxyguanosine, PARP and PARP-85kD segment, while 3AB-treated rats did not. In the liver, both the control group and 3AB group had a higher ratio of PARP-positive stained cells compared with the sham group. The control group, however, had a higher ratio of PARP-85kD segment-staining cells, a very sensitive indicator of apoptosis, than the 3AB and sham groups.Conclusion : We concluded that inhibition of poly(ADP-ribose) polymerase activation could ameliorate multiple organ failure by preserving intracellular ATP levels in ischemia-reperfusion injury.