Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Aug 7, 2010; 16(29): 3642-3650
Published online Aug 7, 2010. doi: 10.3748/wjg.v16.i29.3642
Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats
Valentina Vasina, Massimiliano Broccoli, Maria Grazia Ursino, Donatella Canistro, Luca Valgimigli, Antonio Soleti, Moreno Paolini, Fabrizio De Ponti
Valentina Vasina, Massimiliano Broccoli, Maria Grazia Ursino, Donatella Canistro, Moreno Paolini, Fabrizio De Ponti, Department of Pharmacology, University of Bologna, Bologna 40126, Italy
Luca Valgimigli, Department of Organic Chemistry “A. Mangini”, University of Bologna, Bologna 40126, Italy
Antonio Soleti, Medestea Research, Torino 10121, Italy
Author contributions: Vasina V and Broccoli M performed most of the experiments, analyzed the data, drafted the manuscript and approved the final version of the manuscript; Ursino MG and Canistro D performed some experiments, reviewed and approved the final version of the manuscript; Valgimigli L and Soleti A provided the test compound, reviewed and approved the final version of the manuscript; De Ponti F and Paolini M designed and co-ordinated the study, reviewed and approved the final version of the manuscript.
Supported by A Grant from the University of Bologna (Ricerca Fondamentale Orientata)
Correspondence to: Fabrizio De Ponti, MD, PhD, Department of Pharmacology, University of Bologna, Bologna 40126, Italy. fabrizio.deponti@unibo.it
Telephone: +39-51-2091805 Fax: +39-51-248862
Received: January 27, 2010
Revised: May 29, 2010
Accepted: June 5, 2010
Published online: August 7, 2010
Abstract

AIM: To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC) in the dextran sodium sulphate (DSS) experimental model of ulcerative colitis.

METHODS: Colitis was induced in Sprague Dawley male rats by administration of 5% DSS in drinking water. IAC (30 mg/kg, lipophilic or hydrophilic form) was administered daily (orally or ip) for 6 d until sacrifice. Colonic damage was assessed by means of indirect (Disease Activity Index score) and direct measures (macroscopic and microscopic scores) and myeloperoxidase (MPO) activity. Neutrophil infiltration within the tissue and glutathione S-transferase activity were also investigated.

RESULTS: DSS-induced colitis impaired body weight gain and markedly increased all inflammatory parameters. Six-day treatment with lipophilic IAC significantly reduced intestinal damage caused by inflammation, induced a down-regulation in MPO activity (0.72 ± 0.12 and 0.45 ± 0.12 with lipophilic IAC po and ip, respectively, vs 1.10 ± 0.27 in untreated DSS colitis animals) and minimized DSS-induced neutrophil infiltration, while hydrophilic IAC administered orally did not ameliorate DSS-induced damage.

CONCLUSION: These results support the hypothesis that reactive oxygen metabolites contribute to inflammation and that the radical scavenger IAC has therapeutic potential in inflammatory bowel disease.

Keywords: Dextran sodium sulphate-induced colitis, Oxidative damage, Inflammatory bowel disease, Bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate, Radical scavenger, Animal models