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. 2021 Apr 1;11(1):7378.
doi: 10.1038/s41598-021-86962-0.

Uric acid shown to contribute to increased oxidative stress level independent of xanthine oxidoreductase activity in MedCity21 health examination registry

Masafumi Kurajoh  1 , Shinya Fukumoto  2 , Shio Yoshida  3 , Seigo Akari  4 , Takayo Murase  4 , Takashi Nakamura  4 , Haruka Ishii  5 , Hisako Yoshida  5 , Yuki Nagata  6 , Tomoaki Morioka  3 , Katsuhito Mori  7 , Yasuo Imanishi  3 , Kazuto Hirata  8 , Masanori Emoto  3
Affiliations

Uric acid shown to contribute to increased oxidative stress level independent of xanthine oxidoreductase activity in MedCity21 health examination registry

Masafumi Kurajoh et al. Sci Rep. .

Abstract

Uric acid has both antioxidant and pro-oxidant properties in vitro by scavenging and production of reactive oxygen species (ROS). This cross-sectional study examined whether uric acid possesses effects on oxidative stress under physiological conditions independent of xanthine oxidoreductase (XOR), which is involved in uric acid and ROS production. Serum uric acid level was measured, while plasma XOR activity was determined using our high-sensitive assay in 192 participants (91 males, 101 females) who underwent health examinations and were not taking an antihyperuricemic agent. For antioxidant potential and oxidative stress level, biological antioxidant potential (BAP) and derivative of reactive oxygen metabolites (d-ROMs) in serum, respectively, were measured. Median uric acid level and plasma XOR activity were 5.6 mg/dL and 26.1 pmol/h/mL, respectively, and BAP and d-ROMs levels were 2112.8 μmol/L and 305.5 Carr U, respectively. Multivariable regression analyses revealed no significant association of serum uric acid level with BAP level, whereas serum uric acid level showed a significant association with d-ROMs level independent of plasma XOR activity (p = 0.045), which was prominent in females (p = 0.036; p for interaction = 0.148). Uric acid might contribute to increased oxidative stress independent of XOR activity by increasing ROS production, without affecting ROS scavenging, especially in females.

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Conflict of interest statement

Seigo Akari, Takayo Murase, and Takashi Nakamura of Sanwa Kagaku Kenkyusho Co. Ltd. developed the plasma XOR activity assay used in this study and also performed measurements of that activity. Their involvment does not alter our adherence regarding sharing of data and materials. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Serum uric acid and d-ROMs levels. The serum level of uric acid was significantly associated with d-ROMs level (p = 0.045) and the nonlinear effect of that on d-ROMs level was also significant (p = 0.171). Best fitted line and 95% CI results are shown by a solid line and gray band, respectively. Values for d-ROMs were adjusted according to the median values for age, gender, smoking habit, alcohol drinking habit, VFA, SBP, total cholesterol, HbA1c, eGFR, log HOMA-IR, log hs-CRP, and log plasma XOR activity. d-ROMs derivative of reactive oxygen metabolites, CI confidence interval, VFA visceral fat area, SBP systolic blood pressure, HbA1c glycated hemoglobin, eGFR estimated glomerular filtration rate, HOMA-IR homeostatic model assessment of insulin resistance, hs-CRP high-sensitivity C-reactive protein, XOR xanthine oxidoreductase.
Figure 2
Figure 2
Plasma XOR activity and d-ROMs level. Plasma XOR activity was not significantly associated with d-ROMs level (p = 0.725). Best fitted line and 95% CI results are shown by a solid line and gray band, respectively. Values for d-ROMs were adjusted according to the median values for age, gender, smoking habit, alcohol drinking habit, VFA, SBP, total cholesterol, HbA1c, eGFR, log HOMA-IR, log hs-CRP, and uric acid level. XOR xanthine oxidoreductase, d-ROMs derivative of reactive oxygen metabolites, CI confidence interval, VFA visceral fat area, SBP systolic blood pressure, HbA1c glycated hemoglobin, eGFR estimated glomerular filtration rate, HOMA-IR homeostatic model assessment of insulin resistance, hs-CRP high-sensitivity C-reactive protein.
Figure 3
Figure 3
Serum uric acid and d-ROMs levels stratified by gender. The serum level of uric acid was significantly associated with d-ROMs level in females (p = 0.036) but not in males (p = 0.115). The nonlinear effect of serum uric acid level on d-ROMs level was significant (p = 0.066). Best fitted line and 95% CI results are shown by a solid line and dark gray band, respectively. Values for d-ROMs were adjusted according to the median values for age, smoking habit, alcohol drinking habit, VFA, SBP, total cholesterol, HbA1c, eGFR, log HOMA-IR, log hs-CRP, and log plasma XOR activity after stratification by gender. d-ROMs derivative of reactive oxygen metabolites, CI confidence interval, VFA visceral fat area, SBP systolic blood pressure, HbA1c glycated hemoglobin, eGFR estimated glomerular filtration rate, HOMA-IR homeostatic model assessment of insulin resistance, hs-CRP high-sensitivity C-reactive protein, XOR xanthine oxidoreductase.
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