A highly sensitive assay for xanthine oxidoreductase activity using a combination of [13C2,15N2]xanthine and liquid chromatography/triple quadrupole mass spectrometry

Murase, Takayo; Oka, Mitsuru; Nampei, Mai; Miyachi, Atsushi; Nakamura, Takashi

doi:10.1002/jlcr.3390

Cited by 37 publications

(39 citation statements)

References 21 publications

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“…xanthine with LC/TQMS, as we have previously described [9][10][11] . Briefly, 100-µL aliquots of plasma were purified using a Sephadex G25 column, then mixed with Tris buffer (pH 8.5) containing…”

Section: Participants Referring To the Medcity21 Health Examination mentioning

confidence: 99%

“…We recently developed a highly sensitive test for human plasma XOR activity 9,10 , which utilizes an assay of stable isotope-labeled [ 13 C 2 , 15 N 2 ] xanthine with liquid chromatography (LC)/triple quadrupole mass spectrometry (TQMS), thus is unaffected by the original uric acid concentration in the sample. In our previous study, despite a significant and independent association of plasma XOR activity with serum uric acid level 11 , plasma XOR activity but not serum uric acid level was significantly associated with decreased flow-mediated dilatation (FMD) (preliminary findings), suggesting that XOR contributes to the pathophysiology of endothelial dysfunction through ROS production.…”

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confidence: 99%

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Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Yoshida

Kurajoh

Fukumoto

et al. 2020

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Xanthine oxidoreductase (XoR) inhibitor administration reduces uric acid and reactive oxygen species (RoS) production, and also lowers blood pressure (Bp). However, the associations of plasma XoR activity, uric acid level, and oxidative stress levels with Bp remain unclear. this cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. plasma XoR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. Bp was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-RoMs) levels were simultaneously measured. Median plasma XoR activity, serum uric acid, d-RoMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XoR activity (β = 0.211, p = 0.019), but not serum uric acid (β = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-RoMs level, an independent association of plasma XoR activity with MAp was observed (β = 0.428, p = 0.001 and β = 0.019, p = 0.891, respectively; p for interaction = 0.046). XoR may contribute to the pathophysiology of higher Bp through RoS but not uric acid production, especially in patients with lower oxidative stress.

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Section: Participants Referring To the Medcity21 Health Examination mentioning

confidence: 99%

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confidence: 99%

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Yoshida

Kurajoh

Fukumoto

et al. 2020

Sci Rep

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“…e purpose of the present study was to examine the associations of visceral fat area (VFA), obtained by computed tomography (CT), as well as serum adiponectin level and insulin resistance, assessed by homeostatic model assessment of insulin resistance (HOMA-IR), a reliable surrogate marker for insulin resistance [14,15], with plasma XOR activity using our newly developed assay for determining XOR activity [16,17] in subjects who participated in the MedCity21 health examination registry.…”

Section: Introductionmentioning

confidence: 99%

Insulin Resistance Associated with Plasma Xanthine Oxidoreductase Activity Independent of Visceral Adiposity and Adiponectin Level: MedCity21 Health Examination Registry

Kurajoh

Fukumoto

Murase³

et al. 2019

International Journal of Endocrinology

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Background. Higher levels of uric acid production have been reported in individuals with visceral fat obesity, and obesity is known to enhance xanthine oxidoreductase (XOR) activity, although the precise mechanism remains unclear. We investigated the associations of visceral fat area (VFA), serum adiponectin level, and insulin resistance with plasma XOR activity using our novel highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Methods. This cross-sectional study included 193 subjects (92 males and 101 females) registered in the MedCity21 health examination registry. Plasma XOR activity, serum adiponectin level, and VFA obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results. The mean values for VFA, log HOMA-IR, and log plasma XOR activity were 76.8 ± 45.8 cm2, 0.14 ± 0.30, and 1.50 ± 0.44 pmol/h/mL, respectively. Multiple regression analysis showed that HOMA-IR was significantly (p=0.020) associated with plasma XOR activity independent of other factors, including VFA and adiponectin level, as well as age, sex, alcohol drinking habit, smoking habit, alanine transaminase, HbA1c, and eGFR. The “sex∗HOMA−IR” interaction was not significant (p=0.89), indicating that sex difference does not have an effect on the relationship between HOMA-IR and plasma XOR activity. Conclusions. Our results indicate that insulin resistance is associated with plasma XOR activity and that relationship is independent of visceral adiposity and adiponectin level, suggesting that the development of insulin resistance resulting from increased visceral adiposity and/or reduced serum adiponectin contributes to increased uric acid production by stimulating XOR activity.

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“…Xanthine oxidoreductase activity and oxidative stress in acute heart failure patients Plasma XOR activity is a novel biomarker of metabolic disorders, developed in 2016 by the Sanwa Kagaku Kenkyusho group. 15,16 Their technique enables the stable measurement of tiny amounts of human XOR activity in vivo. 14 However, the value of human XOR activity has not been previously evaluated in patients with severely decompensated AHF.…”

Section: Discussionmentioning

confidence: 99%

Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure requiring intensive care

et al. 2019

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Aims Plasma xanthine oxidoreductase (XOR) activity during the acute phase of acute heart failure (AHF) requires further elucidation. Methods and results One hundred eighteen AHF patients and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analysed. Blood samples were collected within 15 min of admission from AHF patients (AHF group) and control patients who visited a daily cardiovascular outpatient clinic (control group). Plasma XOR activity was compared between the two groups, and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the AHF group (median, 104.0 pmol/h/mL; range, 25.9–423.5 pmol/h/mL) was significantly higher than that in the control group (median, 45.2 pmol/h/mL; range, 19.3–98.8 pmol/h/mL). The multivariate logistic regression model showed that serum uric acid (per 1.0 mg/dL increase, odds ratio: 1.280; 95% confidence interval: 1.066–1.536; P = 0.008) and lactate levels (per 1.0 mmol/L increase, odds ratio: 1.239; 95% confidence interval: 1.040–1.475; P = 0.016) were independently associated with high plasma XOR activity (>300 pg/h/mL) during the acute phase of AHF. Conclusions Plasma XOR activity was extremely high in patients with severely decompensated AHF. This would be associated with a high lactate value and would eventually lead to hyperuricaemia in patients with AHF.

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A highly sensitive assay for xanthine oxidoreductase activity using a combination of [¹³C₂,¹⁵N₂]xanthine and liquid chromatography/triple quadrupole mass spectrometry

Cited by 37 publications

References 21 publications

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Insulin Resistance Associated with Plasma Xanthine Oxidoreductase Activity Independent of Visceral Adiposity and Adiponectin Level: MedCity21 Health Examination Registry

Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure requiring intensive care

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