Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

Okuyama, Tomoko; Shirakawa, Jun; Nakamura, Takashi; Murase, Takayo; Miyashita, Daisuke; Inoue, Ryota; Kyohara, Mayu; Togashi, Yuichi; Terauchi, Yasuo

doi:10.1038/s41598-021-83234-9

Cited by 14 publications

(14 citation statements)

References 39 publications

(45 reference statements)

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“…blood pressure SUA serum uric acid XOR xanthine-oxidoreductase articles have been recently published supporting a correlation between elevated levels of XOR activity, levels of uric acid, and cardiovascular disease. [19][20]…”

Section: Bpmentioning

confidence: 99%

Uric Acid and Hypertension: a Review of Evidence and Future Perspectives for the Management of Cardiovascular Risk

et al. 2022

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Uric acid is the final product of purine metabolism, and its increased serum levels have been directly involved in the pathogenesis and natural history of hypertension. The relationship between elevated uric acid and hypertension has been proven in both animals and humans, and its relevance is already evident in childhood and adolescent population. The mechanism responsible for blood pressure increase in hyperuricemic subjects is implicating both oxidative stress and intracellular urate activity with a primary involvement of XOR (xanthine-oxidoreductase activity). An increase in the relative risk of hypertension has been confirmed by genetic data and by large meta-analyses of epidemiological data. The effects of urate-lowering treatment on blood pressure control in patients with elevated serum uric acid has been investigated in a small number of reliable studies with a large heterogeneity of patient populations and study designs. However, 2 large meta-analyses suggest a significant effect of urate-lowering treatment on blood pressure, thus confirming the significant relationship between high serum urate and blood pressure. The future research should be focused on a more appropriate identification of patients with cardiovascular hyperuricemia by considering the correct cardiovascular threshold of serum urate, the time-course of uricemia fluctuations, and the identification of reliable markers of urate overproduction that could significantly clarify the clinical and therapeutic implications of the interaction between serum uric acid and hypertension.

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Section: Bpmentioning

confidence: 99%

Uric Acid and Hypertension: a Review of Evidence and Future Perspectives for the Management of Cardiovascular Risk

et al. 2022

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“…XOR-derived ROS involvement in the pathogenesis of tissue lesions induced by reperfusion after ischemia is thought to be related to vascular injury resulting from diabetic vascular complications [46]. Taken together, these observations suggest that plasma XOR activity is upregulated in the early period of diabetes and then becomes exhausted with the development of diabetic vascular complications, as suggested in a recent report [47].…”

Section: Discussionmentioning

confidence: 78%

Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes

et al. 2021

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To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None were currently taking XOR inhibitors. XOR activity of fasting blood samples was assayed using a stable isotope-labeled substrate and LC-TQMS. JMP Clinical version 5.0. was used for analysis. We analyzed 54 patients. Mean age was 64.7 years, mean body mass index was 26.0 kg/m2, and mean glycated hemoglobin was 9.4%. The logarithmically transformed plasma XOR activity (ln-XOR) correlated positively with hypoxanthine, xanthine, visceral fatty area, and liver dysfunction but negatively with HDL cholesterol. ln-XOR correlated negatively with diabetes duration and maximum intima-media thickness. Stepwise multiple regression analysis revealed ln-XOR to be among selected explanatory factors for various NCS parameters. Receiver operating characteristic curves showed the discriminatory power of ln-XOR. Principal component analysis revealed a negative relationship of ln-XOR with F-waves as well as positive relationships of ln-XOR with hepatic steatosis and obesity-related disorders. Taken together, our results show plasma XOR activity to be among potential disease status predictors in T2DM patients. Plasma XOR activity measurements might reliably detect pre-symptomatic DSP.

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“…Additionally, scopoletin administered either by intraperitoneal injection or by oral gavage of scopoletin-loaded micelles was shown to correct hyperuricemia in mice through two separate mechanisms, namely inhibiting hepatic XO activity and enhancing uric acid excretion by the kidney ( 201 , 202 ). Notably, XO activity is associated with obesity-related metabolic dysfunction, and XO inhibitors typically prescribed for gout or hyperuricemia are proving to be effective in mitigating cardiovascular and renal complications of diabetes ( 504 , 507 , 508 ).…”

Section: Effects Of Bioactive Compounds Found In a Scopariamentioning

confidence: 99%

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

et al. 2022

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Botanicals have a long history of medicinal use for a multitude of ailments, and many modern pharmaceuticals were originally isolated from plants or derived from phytochemicals. Among these, artemisinin, first isolated from Artemisia annua, is the foundation for standard anti-malarial therapies. Plants of the genus Artemisia are among the most common herbal remedies across Asia and Central Europe. The species Artemisia scoparia (SCOPA) is widely used in traditional folk medicine for various liver diseases and inflammatory conditions, as well as for infections, fever, pain, cancer, and diabetes. Modern in vivo and in vitro studies have now investigated SCOPA’s effects on these pathologies and its ability to mitigate hepatotoxicity, oxidative stress, obesity, diabetes, and other disease states. This review focuses on the effects of SCOPA that are particularly relevant to metabolic health. Indeed, in recent years, an ethanolic extract of SCOPA has been shown to enhance differentiation of cultured adipocytes and to share some properties of thiazolidinediones (TZDs), a class of insulin-sensitizing agonists of the adipogenic transcription factor PPARγ. In a mouse model of diet-induced obesity, SCOPA diet supplementation lowered fasting insulin and glucose levels, while inducing metabolically favorable changes in adipose tissue and liver. These observations are consistent with many lines of evidence from various tissues and cell types known to contribute to metabolic homeostasis, including immune cells, hepatocytes, and pancreatic beta-cells. Compounds belonging to several classes of phytochemicals have been implicated in these effects, and we provide an overview of these bioactives. The ongoing global epidemics of obesity and metabolic disease clearly require novel therapeutic approaches. While the mechanisms involved in SCOPA’s effects on metabolic, anti-inflammatory, and oxidative stress pathways are not fully characterized, current data support further investigation of this plant and its bioactives as potential therapeutic agents in obesity-related metabolic dysfunction and many other conditions.

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Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

Cited by 14 publications

References 39 publications

Uric Acid and Hypertension: a Review of Evidence and Future Perspectives for the Management of Cardiovascular Risk

Uric Acid and Hypertension: a Review of Evidence and Future Perspectives for the Management of Cardiovascular Risk

Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

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