5-Aminoisoquinolinone reduces colon injury by experimental colitis

Salvatore Cuzzocrea, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, N. S A Patel, Carmelo Muià, Michael D. Threadgill, Angelina De Sarro, Christoph Thiemermann

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)464-473
Number of pages10
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume370
Issue number6
DOIs
Publication statusPublished - Dec 2004

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Keywords

  • 5-AIQ
  • Colitis
  • ICAM-1
  • Inflammatory infiltration
  • PARP

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cuzzocrea, S., Mazzon, E., Di Paola, R., Genovese, T., Patel, N. S. A., Muià, C., Threadgill, M. D., De Sarro, A., & Thiemermann, C. (2004). 5-Aminoisoquinolinone reduces colon injury by experimental colitis. Naunyn-Schmiedeberg's Archives of Pharmacology, 370(6), 464-473. https://doi.org/10.1007/s00210-004-1002-x