Poly (ADP-ribose) polymerase (PARP), a nuclear
enzyme activated by strand breaks in
DNA, plays an important role in the colon injury associated with experimental
colitis. The aim of the present study was to examine the effects of
5-aminoisoquinolinone (5-AIQ), a novel and potent inhibitor of PARP activity, in the development of experimental
colitis. To address this question, we used an experimental model of
colitis, induced by
dinitrobenzene sulfonic acid (
DNBS). Compared with
DNBS-treated mice, mice treated with
5-AIQ (3 mg/kg i.p.) or
3-aminobenzamide (3-AB; 10 mg/kg i.p. twice a day) and subjected to
DNBS-induced
colitis experienced a significantly lower rate in the extent and severity of the histological signs of colon injury.
DNBS-treated mice experienced
diarrhea and
weight loss. Four days after administration of
DNBS, the mucosa of the colon exhibited large areas of
necrosis. Neutrophil infiltration (determined by histology as well as an increase in
myeloperoxidase [MPO] activity in the mucosa) was associated with an up-regulation of
intercellular adhesion molecule-1 (ICAM-1). Immunohistochemistry for PAR showed an intense staining in the inflamed colon. On the contrary, the treatment of
DNBS-treated mice with
5-AIQ or with 3-AB significantly reduced the degree of hemorrhagic
diarrhea and
weight loss caused by administration of
DNBS.
5-AIQ also caused a substantial reduction in the degree of colon injury, in the rise in MPO activity (mucosa), in the increase in staining (immunohistochemistry) for PAR, as well as in the up-regulation of
ICAM-1 caused by
DNBS in the colon. Thus,
5-AIQ treatment reduces the degree of
colitis caused by
DNBS. We propose that
5-AIQ treatment may be useful in the treatment of
inflammatory bowel disease.