Formation of 8-nitroguanine in blood of patients with inflammatory gouty arthritis

Abstract

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 μg/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/μg 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.