Prevention of acetic acid-induced colitis by desferrithiocin analogs in a rat model.
Iron contributes significantly to the formation of reactive oxygen species via the Fenton reaction. Therefore, we assessed whether a series of desferrithiocin analogs, both carboxylic acids and hydroxamates, could (1) either promote or diminish the iron-mediated oxidation of ascorbate, (2) quench a model radical species, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), and (3) when applied topically, prevent acetic acid-induced colitis in rats. Surprisingly, most of the desferrithiocin analogs inhibited the Fenton reaction to an approximately equivalent degree; however, substantial differences were observed in the capacity of the analogs to scavenge the model radical cation. Four carboxylic acid desferrithiocin analogs and their respective N-methylhydroxamates were tested along with desferrioxamine and Rowasa, a currently accepted topical therapeutic agent for inflammatory bowel disease (IBD), in a rodent model of acetic acid-induced colitis. The colonic damage was quantitated by two independent measurements. Although neither radical scavenging nor prevention of Fenton chemistry was a definitive predictor of in vivo efficacy, the overall trend is that desferrithiocin analogs substituted with an N-methylhydroxamate in the place of the carboxylic acid are both better free radical scavengers and more active against acetic acid-induced colitis. These results represent an intriguing alternative avenue to the development of improved IBD therapeutic agents.[1]References
- Prevention of acetic acid-induced colitis by desferrithiocin analogs in a rat model. Bergeron, R.J., Wiegand, J., Weimar, W.R., Nguyen, J.N., Sninsky, C.A. Dig. Dis. Sci. (2003) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
