BACKGROUND: NOx causes DNA damage due to an inflammatory effect of gouty arthritis. We investigated the concentration of 8-nitroguanine (8-NO(2)-G) in the blood of patients with arthritis. METHODS: Subjects were divided into 3 groups: (1) high inflammatory (HI) group (n = 21) with hyperuricemia (mean, 8.9 mg/dl) and leukocytosis, (2) low inflammatory (LI) group (n = 14) with mild hyperuricemia (mean, 7.6 mg/dl) but normal leukocyte count, (3) non-inflammatory (NI) healthy control (n = 19) with mean serum uric acid concentration 5.3 mg/dl and normal leukocyte count. Serum C-reactive protein (CRP) concentrations were measured by a visual agglutination method. The blood concentrations of 8-NO(2)-G were determined by high performance liquid chromatography-electrochemical detection and were compared between groups. RESULTS: There was significant difference in percentage of positive CRP (NI: 55.6%, LI: 64.3%, HI: 100%, p = 0.003) between the 3 groups. The leukocyte count (mean +/- S.E., NI: 7400 +/- 528, LI: 7686 +/- 433, HI: 10952 +/- 691/mm(3), p < 0.001), uric acid (NI: 5.3 +/- 0.24, LI: 7.6 +/- 0.4, HI: 8.9 +/- 0.36 mg/dl, p < 0.001), NO(2) (NI: 6.5 +/- 1.2, LI: 11.1 +/- 2.9, HI: 35.6 +/- 5.1 microg/ml, p < 0.001) and the 8-NO(2)-G (NI: 0.08 +/- 0.03; LI: 0.34 +/- 0.13; HI: 0.59 +/- 0.09 ng/microg DNA, p = 0.002) were significantly increased by inflammation. CONCLUSION: Gouty inflammation induces DNA damage by increasing 8-NO(2)-G through endogenous NO and ROS formation.
BACKGROUND:NOx causes DNA damage due to an inflammatory effect of gouty arthritis. We investigated the concentration of 8-nitroguanine (8-NO(2)-G) in the blood of patients with arthritis. METHODS: Subjects were divided into 3 groups: (1) high inflammatory (HI) group (n = 21) with hyperuricemia (mean, 8.9 mg/dl) and leukocytosis, (2) low inflammatory (LI) group (n = 14) with mild hyperuricemia (mean, 7.6 mg/dl) but normal leukocyte count, (3) non-inflammatory (NI) healthy control (n = 19) with mean serum uric acid concentration 5.3 mg/dl and normal leukocyte count. Serum C-reactive protein (CRP) concentrations were measured by a visual agglutination method. The blood concentrations of 8-NO(2)-G were determined by high performance liquid chromatography-electrochemical detection and were compared between groups. RESULTS: There was significant difference in percentage of positive CRP (NI: 55.6%, LI: 64.3%, HI: 100%, p = 0.003) between the 3 groups. The leukocyte count (mean +/- S.E., NI: 7400 +/- 528, LI: 7686 +/- 433, HI: 10952 +/- 691/mm(3), p < 0.001), uric acid (NI: 5.3 +/- 0.24, LI: 7.6 +/- 0.4, HI: 8.9 +/- 0.36 mg/dl, p < 0.001), NO(2) (NI: 6.5 +/- 1.2, LI: 11.1 +/- 2.9, HI: 35.6 +/- 5.1 microg/ml, p < 0.001) and the 8-NO(2)-G (NI: 0.08 +/- 0.03; LI: 0.34 +/- 0.13; HI: 0.59 +/- 0.09 ng/microg DNA, p = 0.002) were significantly increased by inflammation. CONCLUSION: Gouty inflammation induces DNA damage by increasing 8-NO(2)-G through endogenous NO and ROS formation.