GPI 6150, a PARP inhibitor, reduces the colon injury caused by dinitrobenzene sulfonic acid in the rat

Emanuela Mazzon, Laura Dugo, Jia He Li, Rosanna Di Paola, Tiziana Genovese, Achille P. Caputi, Jie Zhang, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Poly (ADP-ribose) polymerase, a nuclear enzyme activated by DNA strand breaks, has been shown to play an important role in the pathogenesis of inflammatory bowel disease. Here we investigate the effects of 1,11b-dihydro-[2H]benzopyrano [4,3,2-de]isoquinolin-3-one (GPI 6150), a new poly (ADP-ribose) polymerase inhibitor, in animal models of experimental colitis. Colitis was induced in rats by intra-colonic instillation of dinitrobenzene sulfonic acid. Rats experienced hemorrhagic diarrhea and weight loss. At 4 days after administration of dinitrobenzensulfonic acid, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology and an increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1. Immunohistochemistry for poly (ADP-ribose) showed an intense staining in the inflamed colon. GPI 6150 (20 or 40mg/kg daily, i.p.) significantly reduced the degree of hemorrhagic diarrhea and weight loss caused by administration of dinitrobenzensulfonic acid. GPI 6150 also caused a substantial reduction of (i) the degree of colon injury, (ii) the rise in myeloperoxidase activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde, (iv) the increase in staining (immunohistochemistry) for poly (ADP-ribose), as well as (v) the upregulation of ICAM-1 and P-selectin caused by dinitrobenzensulfonic acid in the colon. Thus, GPI 6150 reduces the degree of colitis caused by dinitrobenzensulfonic acid. We propose that GPI 6150 may be useful in the treatment of inflammatory bowel disease.

Original languageEnglish
Pages (from-to)327-337
Number of pages11
JournalBiochemical Pharmacology
Volume64
Issue number2
DOIs
Publication statusPublished - Jul 15 2002

Fingerprint

Dinitrobenzenes
Sulfonic Acids
Rats
Colon
Wounds and Injuries
Colitis
Poly Adenosine Diphosphate Ribose
Mucous Membrane
Acids
Intercellular Adhesion Molecule-1
Inflammatory Bowel Diseases
Peroxidase
Weight Loss
Diarrhea
Up-Regulation
Immunohistochemistry
Staining and Labeling
Histology
DNA Breaks
P-Selectin

Keywords

  • Bowel disease
  • Free radicals
  • GPI 6150
  • Inflammation
  • Nitric oxide
  • Poly (ADP-ribose) synthethase

ASJC Scopus subject areas

  • Pharmacology

Cite this

GPI 6150, a PARP inhibitor, reduces the colon injury caused by dinitrobenzene sulfonic acid in the rat. / Mazzon, Emanuela; Dugo, Laura; Li, Jia He; Di Paola, Rosanna; Genovese, Tiziana; Caputi, Achille P.; Zhang, Jie; Cuzzocrea, Salvatore.

In: Biochemical Pharmacology, Vol. 64, No. 2, 15.07.2002, p. 327-337.

Research output: Contribution to journalArticle

Mazzon, E, Dugo, L, Li, JH, Di Paola, R, Genovese, T, Caputi, AP, Zhang, J & Cuzzocrea, S 2002, 'GPI 6150, a PARP inhibitor, reduces the colon injury caused by dinitrobenzene sulfonic acid in the rat', Biochemical Pharmacology, vol. 64, no. 2, pp. 327-337. https://doi.org/10.1016/S0006-2952(02)01075-4
Mazzon, Emanuela ; Dugo, Laura ; Li, Jia He ; Di Paola, Rosanna ; Genovese, Tiziana ; Caputi, Achille P. ; Zhang, Jie ; Cuzzocrea, Salvatore. / GPI 6150, a PARP inhibitor, reduces the colon injury caused by dinitrobenzene sulfonic acid in the rat. In: Biochemical Pharmacology. 2002 ; Vol. 64, No. 2. pp. 327-337.
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