Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock

Rosanna Di Paola, Emanuela Mazzon, Weizheng Xu, Tiziana Genovese, Dana Ferrraris, Carmelo Muià, Concetta Crisafulli, Jie Zhang, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme activated by DNA strand breaks, plays a detrimental role during inflammation. As inflammation is important in the development of colitis and ischemia/reperfusion (I/R) injury of the intestine, we investigated the effects of 10-(4-methyl-piperazin-1- ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one (GPI 15427) and 2-(4-methyl-piperazin-1-yl)-5H-benzo[c][1,5]naphthyridin-6-one (GPI 16539), two novel and potent inhibitors of PARP-1, in a rat model of gut injury and inflammation, splanchnic artery occlusion (SAO)shock and dinitrobenzene sulfonic acid (DNBS)-induced colitis. We report here for the first time that post-injury administration of GPI 15427 and GPI 16539 exerts potent anti-inflammatory effects by reducing inflammatory cell infiltration and histological injury, and delaying the development of clinical signs in both in vivo models. Furthermore, GPI 15427 and GPI 16539 treatment diminished the accumulation of poly(ADP-ribose) in the ileum of splanchnic artery occlusion-shocked rats and in the colons of dinitrobenzene sulfonic acid-treated rats. Thus, GPI 15427 and GPI 16539 exhibited anti-inflammation activity against damage caused by intestinal ischemia/reperfusion and colitis. GPI 15427 and GPI 16539 may be useful for treating gut ischemia and inflammation.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalEuropean Journal of Pharmacology
Volume527
Issue number1-3
DOIs
Publication statusPublished - Dec 19 2005

Fingerprint

Colitis
Shock
Inflammation
Dinitrobenzenes
Sulfonic Acids
Viscera
Wounds and Injuries
Ischemia
Arteries
Poly Adenosine Diphosphate Ribose
DNA Breaks
Reperfusion Injury
Ileum
Reperfusion
Intestines
Poly (ADP-Ribose) Polymerase-1
2-(4-methylpiperazin-1-yl)-5H-benzo(c)(1,5)naphthyridin-6-one
GPI 15427
Poly(ADP-ribose) Polymerase Inhibitors
Colon

Keywords

  • Colitis
  • GPI 15427
  • GPI 16539
  • Ischemia/Reperfusion
  • Myeloperoxidase
  • PARP-1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock. / Di Paola, Rosanna; Mazzon, Emanuela; Xu, Weizheng; Genovese, Tiziana; Ferrraris, Dana; Muià, Carmelo; Crisafulli, Concetta; Zhang, Jie; Cuzzocrea, Salvatore.

In: European Journal of Pharmacology, Vol. 527, No. 1-3, 19.12.2005, p. 163-171.

Research output: Contribution to journalArticle

Di Paola, R, Mazzon, E, Xu, W, Genovese, T, Ferrraris, D, Muià, C, Crisafulli, C, Zhang, J & Cuzzocrea, S 2005, 'Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock', European Journal of Pharmacology, vol. 527, no. 1-3, pp. 163-171. https://doi.org/10.1016/j.ejphar.2005.09.055
Di Paola, Rosanna ; Mazzon, Emanuela ; Xu, Weizheng ; Genovese, Tiziana ; Ferrraris, Dana ; Muià, Carmelo ; Crisafulli, Concetta ; Zhang, Jie ; Cuzzocrea, Salvatore. / Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock. In: European Journal of Pharmacology. 2005 ; Vol. 527, No. 1-3. pp. 163-171.
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