Oxidation of Uric Acid in Rheumatoid Arthritis: Is Allantoin a Marker of Oxidative Stress?

Abstract

Free radicals are implicated in many diseases including atherosclerosis, cancer and also in rheumatoid arthritis. Reaction of uric acid with free radicals, such as hydroxyl radical and hypochlorous acid (HOCl) results in allantoin production. In this study, we measured the serum allantoin levels, oxidation products of uric acid, as a marker of free radical generation in rheumatoid arthritis. Fasting blood samples were obtained from 21 rheumatoid patients and 15 healthy controls. In this study, the serum allantoin and uric acid levels were measured by a gas chromatography-mass spectrometry method and the ratios were calculated. The mean allantoin and uric acid levels and ratios in the patient group were 22.1 +/- 11.3, 280.5 +/- 65.0 and 8.0 +/- 3.7 microM, while in the control group they were 13.6 +/- 6.3, 278.3 +/- 53.6 and 4.9 +/- 2.1 microM, respectively. The effects of gender, age, menopausal status, duration of disease and medications on serum allantoin and uric acid levels of the patient and control groups were studied. Our results suggest that uric acid acts as a free radical scavenger and thus is converted to allantoin. Increased allantoin levels suggest the possible involvement of free radicals in rheumatoid arthritis.

Today’s oxidative stress markers

“…Concentration of allantoin was used as a marker for oxidation of uric acid. The levels of allantoin determined by the authors of the study ranged 17.0-27.2 µmol/l in patients and 10.1-17.0 µmol/l in healthy adults [24]. Much lower concentrations of allantoin in plasma were found by Turner et al [25].…”

“…Allantoin concentrations are estimated at the level of a few/several micromoles per litre. However, older studies showed much higher concentrations of allantoin [16,24] than those performed by the more recent instrumental techniques [21,25]. Current methods, both liquid and gas chromatography with mass spectrometry are more sensitive and more specific.…”

“…Yardim et al [24] performed a study, in which they analysed the participation of ROS in rheumatoid arthritis. Concentration of allantoin was used as a marker for oxidation of uric acid.…”

“…It requires the use of sensitive and specific analytical techniques [21]. Allantoin was determined by means of capillary zone electrophoresis (CZE) [27], enzymatic assay and enzyme cycling method [28], capillary electrophoresis with UV detection (CE-UV) [29], high performance liquid chromatography -UV detection (HPLC-UV) [9,30], ultra performance liquid chromatography -tandem mass spectrometry (HPLC/UPLC-MS/MS) [10][11][12][13][14]21], and gas chromatography -mass spectrometry (GC-MS) [20,24,31], and allantoin is detected readily in urine, plasma, and synovial fluid [25].…”

Correlation of Age-Related Metabonomic Changes in 1H NMR Serum and Urine Profiles of Rats with Cognitive Function

“…We observed significantly higher levels of allantoin in the aged rat urine as compared with young. The elevated allantoin content is again a reflection of increased oxidative stress in the aged rats [40][41][42].…”