Oxygen free radicals interact with indomethacin to cause gastrointestinal injury.
In the present study it was shown that, unlikely MK447, a known oxygen free radical compound, PGE2 is much less effective against indomethacin-induced G.I. ulcers than against ethanol damage. It seems likely that factors other than PG deficiency (such as oxygen free radicals), could be involved in the pathogenesis of NSAID-induced G.I. damage. Some compounds that can capture free radicals (aminopyrine, thiourea and its derivative, MK 447) or that inhibit the lipoxygenase pathway (MK 447, salicylazosulfapyridine, BW 755, benoxaprofen) are able to abolish indomethacin-induced G.I. damage. After irradiation with hydroxyl free radicals, indomethacin reacts with them to cause marked G.I. injury, even at a submaximal dose, one poorly ulcerogenic by itself. The above findings suggest that oxygen free radicals are one of the causal factors in the formation of NSAID-induced G.I. side effects. Some of the data in this paper were presented at Fermo, August 31, 1984 (Advanced course on 'oxygen and sulfur radicals in chemistry and medicine') and at the 9th Iuphar International Congress of Pharmacology in London, July 30, 1984.
Del Soldato
P
P
Foschi
D
D
Benoni
G
G
Scarpignato
C
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D004064:Digestive System / Q000187:drug effects / Q000473:pathology*; D015232:Dinoprostone; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005609:Free Radicals; D007213:Indomethacin / Q000633:toxicity*; D010100:Oxygen / Q000633:toxicity*; D010437:Peptic Ulcer / Q000139:chemically induced*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced*
D000893:Anti-Inflammatory Agents; D005609:Free Radicals; D011458:Prostaglandins E; D002084:Butylated Hydroxytoluene; D000431:Ethanol; C013753:2-aminomethyl-4-t-butyl-6-iodophenol; D015232:Dinoprostone; D010100:Oxygen; D007213:Indomethacin