Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry

Kurajoh, Masafumi; Fukumoto, Shinya; Emoto, Masanori; Murase, Takayo; Nakamura, Takashi; Ishihara, Takuma; Go, Hirofumi; Yamamoto, Keiji; Nakatani, Shinya; Tsuda, Akihiro; Yamada, Shinsuke; Morioka, Tomoaki; Mori, Katsuhito; Imanishi, Yasuo; Inaba, Masaaki

doi:10.1515/cclm-2019-0199

Cited by 21 publications

(21 citation statements)

References 36 publications

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“…Consistent with those reports, plasma uric acid level in the present study was not significantly or independently associated with BP or hypertension (Tables 2 and 5), thus uric acid may not have an important role in the pathophysiology of hypertension in humans. It is also important to note that though previous epidemiological findings have indicated an association of serum uric acid with BP, those findings might have been based on the association of XOR activity with BP, since our previous results demonstrated a significant and independent association of plasma XOR activity with serum uric acid level 11 .…”

Section: Or (95% Ci) Pmentioning

confidence: 61%

“…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.…”

mentioning

confidence: 76%

“…Study design. The MedCity21 health examination registry was initiated in April 2015 in a comprehensive manner to elucidate the causes of various diseases occurring in adults, including cancer, diabetes mellitus, cardiovascular disease, cerebrovascular disease, mental disorders, dyslipidemia, hypertension, hyperuricemia, obesity, chronic respiratory disease, liver disease, digestive disease, gynecological diseases, and skin disease, for development of advanced diagnostic techniques, as well as treatment and prevention methods for affected patients 11,[41][42][43] . Individuals who underwent comprehensive medical examinations as part of MedCity21 at the Osaka City University Hospital Advanced Medical Center for Preventive Medicine (Osaka, Japan) were registered.…”

Section: Methodsmentioning

confidence: 99%

“…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%

“…VFA values were calculated using the fatPointer software package, ver. 2 (Hitachi, Ltd., Tokyo, Japan), as previously described 11 .…”

Section: Participants Referring To the Medcity21 Health Examination mentioning

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

Sci Rep

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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: Or (95% Ci) Pmentioning

confidence: 61%

mentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Section: Participants Referring To the Medcity21 Health Examination mentioning

confidence: 99%

“…VFA values were calculated using the fatPointer software package, ver. 2 (Hitachi, Ltd., Tokyo, Japan), as previously described 11 .…”

Section: Participants Referring To the Medcity21 Health Examination mentioning

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

Sci Rep

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Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers

Liang,

Wu,

Gao

et al. 2023

Molecular Nutrition Food Res

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BackgroundOral inosine loading is a new method to evaluate the effects of purine on urate metabolism. However, individuals respond differently to acute purine intake, and the effects on the metabolism of other purines remain to be explored.Methods35 male participants are recruited. Participants received 500 mg of inosine orally after an overnight fast, and blood and urine samples are collected before and at various time points over 180 min after inosine administration.ResultsThe serum urate concentration is significantly different between the hyperuricemia (n = 14) and non‐hyperuricemia (n = 16) groups before inosine intake, but there is no in urate change after inosine intake. When grouped according to the baseline estimated glomerular filtration rate (eGFR), the increase in urate level in the high‐eGFR group is significantly higher than that in the low‐eGFR group (p = 0.047). The high‐eGFR group showed higher levels of serum xanthine and xanthine oxidase (XOD), the key enzyme in urate synthesis, after inosine loading (p < 0.01).ConclusionsThe increase in urate level is positively related to eGFR after oral acute inosine administration, which may have been due to a higher level of XOD.

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Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions

Rendić¹,

Crouch

Guengerich

2022

Arch Toxicol

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This is an overview of the metabolic reactions of drugs, natural products, physiological compounds, and other (general) chemicals catalyzed by flavin monooxygenase (FMO), monoamine oxidase (MAO), NAD(P)H quinone oxidoreductase (NQO), and molybdenum hydroxylase enzymes (aldehyde oxidase (AOX) and xanthine oxidoreductase (XOR)), including roles as substrates, inducers, and inhibitors of the enzymes. The metabolism and bioactivation of selected examples of each group (i.e., drugs, “general chemicals,” natural products, and physiological compounds) are discussed. We identified a higher fraction of bioactivation reactions for FMO enzymes compared to other enzymes, predominately involving drugs and general chemicals. With MAO enzymes, physiological compounds predominate as substrates, and some products lead to unwanted side effects or illness. AOX and XOR enzymes are molybdenum hydroxylases that catalyze the oxidation of various heteroaromatic rings and aldehydes and the reduction of a number of different functional groups. While neither of these two enzymes contributes substantially to the metabolism of currently marketed drugs, AOX has become a frequently encountered route of metabolism among drug discovery programs in the past 10–15 years. XOR has even less of a role in the metabolism of clinical drugs and preclinical drug candidates than AOX, likely due to narrower substrate specificity.

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Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry

Cited by 21 publications

References 36 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

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers

Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions

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