Urinary 8-hydroxydeoxyguanosine excretion as a non-invasive marker of neutrophil activation in animal models of inflammatory bowel disease.
BACKGROUND
Because free radicals contribute to ulcerative colitis and Crohn's disease, assessing oxidative load in vivo could provide a surrogate marker of inflammation and disease status.


METHODS
Electrochemical high-performance liquid chromatography was used to study urinary excretion of 8-hydroxydeoxyguanosine (8-OH-dGUA), formed by reaction of hydroxyl radicals with native DNA, in 2,4,6-trinitrobenzene-sulfonic acid (TNBS) and dextran sulfate (DSS) rat models of bowel inflammation. Bowel myeloperoxidase (MPO) and histopathology were also assessed.


RESULTS
TNBS enema (75 mg/kg in 50% ethanol) and oral DSS (6% via drinking water) both yielded an inflammatory response reflected by increases in bowel MPO that were significantly correlated with tissue injury. In both models urinary 8-OH-dGUA excretion was significantly correlated with bowel MPO activity and epithelial injury and remained at control levels when neutrophils (PMN) were eliminated, whereas epithelial injury and crypt erosion persisted despite neutropenia.


CONCLUSIONS
Urinary 8-OH-dGUA excretion directly reflects PMN activation in vivo, thereby providing a non-invasive surrogate marker for inflammation in these models which is more indicative of PMN activation than either MPO activity, which does not distinguish inactive from active MPO, or epithelial status, which is independent of PMN activation in both models.
Dykens
J A
JA
Immunopathology, Parke Davis Pharmaceutical Research, Warner-Lambert Co., Ann Arbor, Michigan, USA.
Baginski
T J
TJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D016264:Dextran Sulfate; D004733:Enema; D017665:Hydroxyl Radical / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology / Q000652:urine*; D007422:Intestines / Q000201:enzymology; D008297:Male; D018375:Neutrophil Activation; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
D017665:Hydroxyl Radical; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D009195:Peroxidase; D003849:Deoxyguanosine