Salicylate hydroxylation as an indicator of hydroxyl radical generation in dextran sulfateinduced colitis

Blackburn, AC; Doe, WF; Buffinton, GD

doi:10.1016/s0016-5085(98)83803-1

Cited by 1 publication

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“…Thus, CPI-1189 might work as a radical scavenger to directly protect sensitive targets in cells from damage caused by reactive oxygen species. However, CPI-1189 is not a particularly effective scavenger and the available evidence is that hydroxyl radicals are not produced to any appreciable extent following treatment with DSS [21] . More likely, a potent protection by CPI-1189 against the deleterious effects of cytokines such as TNF-α is responsible for the activity of this agent in the DSS model.…”

Section: Evaluation Of the Dose-dependent Protection Of Cpi-1189 In Tmentioning

confidence: 99%

CPI-1189 Protects Against Dextran Sulfate Sodium-induced Colitis in Mice

Meerveld¹,

Tyler²

2006

American J. of Pharmacology and Toxicology

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Nitrone-related therapeutics (NRTs) represent a new class of small molecules potentially effective in the treatment of inflammatory bowel disease (IBD) by protecting cells from damage caused by excess inflammation and/or oxidative stress. The goal of this study was to determine the efficacy and potency of CPI-1189, a novel therapeutic agent, in dextran sulfate sodium (DSS)-induced colitis in mice. Mice received oral doses of either CPI-1189 (3, 10, or 30 mg kg¯1) or the methyl cellulose vehicle along with 3% dextran sulfate in their drinking water. Assessment of colitis was by calculation of a disease activity index (DAI) and by histological observations. Signs of colitis in vehicle-treated mice were evident by day 3 using the DAI and with histological confirmation on day 7. In mice given CPI-1189, there was a significant and dose-dependent improvement in all signs of colitis with an overall protection of approximately 50%. These observations suggest that CPI-1189 is a novel, orally active, therapeutic agent that could be developed for the treatment of crohn's disease and ulcerative colitis in humans.

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Section: Evaluation Of the Dose-dependent Protection Of Cpi-1189 In Tmentioning

confidence: 99%