trichloromethylperoxy-radical and Inflammation

Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD).

Topics: Aminosalicylic Acids; Anions; Antioxidants; Electrons; Free Radical Scavengers; Free Radicals; Glutathione; Hydrogen-Ion Concentration; Hydroxyl Radical; Inflammation; Inflammatory Bowel Diseases; Kinetics; Lipid Peroxidation; Mesalamine; Models, Chemical; Oxygen; Peroxides; Pulse Radiolysis; Spectrophotometry; Sulfapyridine; Sulfasalazine; Time Factors