Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation

Kaneko, Chris R. S.; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Ken‐ichi; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

doi:10.1016/j.bbagen.2016.11.042

Cited by 42 publications

(29 citation statements)

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“…It has been reported that metabolism of fructose stimulates UA production, since transient ATP depletion commonly occurs with the generation of AMP [55] and reduced UA excretion [56]. Briefly, during fructose metabolism, fructose is phosphorylated into fructose 1-phosphate in a reaction catalyzed by fructokinase primarily in the liver.…”

Section: Fructose Metabolism and The Mechanisms By Which Fructose mentioning

confidence: 99%

“…Moreover, long-term fructose administration suppresses renal excretion of UA, resulting in elevated serum UA levels [19]. Kaneko and colleagues found that a single administration of fructose affects the excretion of UA to the intestinal lumen, inducing the suppression of BCRP dimerization by reactive oxygen species (ROS)-derived production of dinucleotide phosphate (NADPH) oxidase (NOX) [56]. …”

Section: Fructose Metabolism and The Mechanisms By Which Fructose mentioning

confidence: 99%

“…Several in vitro and in vivo studies have shown that high fructose consumption increases blood UA levels [4,55,56,91]. In addition, consuming fructose over several days [70] and intravenous fructose administration [92] are both associated with an increase in fasting serum UA levels.…”

Section: Evidence From Clinical Studies Relevance For Humansmentioning

confidence: 99%

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Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

et al. 2017

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There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5–6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders.

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Section: Fructose Metabolism and The Mechanisms By Which Fructose mentioning

confidence: 99%

Section: Fructose Metabolism and The Mechanisms By Which Fructose mentioning

confidence: 99%

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Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

et al. 2017

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“…The current study further found that high dose UA directly impaired NO generation in cultured human umbilical vein ECs, suggesting that hyperuricemia impairs vascular function by a mechanism of inhibition of NO production. In this regard, high dose may increase the activity of nicotinamide adenine dinucleotide phosphate oxidase that prompts oxidative stress and decreases the bioavailability of NO (22). Further, hyperuricemia impairs vascular function by increasing inflammation cytokine expression in IL-6, IL-8 and TNF-α.…”

Section: Discussionmentioning

confidence: 99%

The role of hyperuricemia on vascular endothelium dysfunction

Zhen

Gui

2017

Biomedical Reports

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Abstract. Hyperuricemia appears to be associated with an increased risk for cardiovascular disease and associated mortality. Population epidemiological data support a causal link between hyperuricemia and cardiovascular disease. Endothelium injury could be one of the potential mechanisms in hyperuricemia-induced cardiovascular disease. However, the specific role of uric acid (UA) in the impairment of vascular relaxation and its signal transduction pathway has not been examined. The authors investigated the role of UA on vascular relaxation, nitric oxide (NO) production and expression of proinflammatory cytokines. Brachial flow-mediated dilation and nitroglycerine-mediated dilation were measured by B-mode ultrasound with 10 megahertz linear-array transducer from 21 patients with hyperuricemia and 16 control subjects. Human umbilical vein endothelial cells (ECs) were incubated with UA (5-15 mg/dl) with or without nuclear factor (NF)-κB inhibitor II. Hyperuricemia inhibited brachial flow-mediated dilation. While UA significantly inhibited NO expression with time course-and dose-dependent manner in the cultured ECs, 10 mg/dl UA also increased expression of inflammation cytokine interleukin (IL)-6, IL-8 and tumor necrosis factor-α in vitro. These abnormalities were associated with UA-induced activation of transcription factor NF-κB. Furthermore, NF-κB inhibitor II prevented UA-induced reduction of NO and increased inflammation cytokines. These data suggested hyperuricemia-induced endothelium injury and vascular dysfunction by a reduction of NO and expression of inflammatory cytokines through the NF-κB pathway. IntroductionHyperuricemia has been linked to cardiovascular disease (CVD) recent since it is regarded as an independent risk factors in the contribution of CVD including vascular disease, hypertension, metabolic syndrome and renal disease (1). Generally, uric acid (UA) levels >7 mg/dl in males and >6 mg/dl in females are considered as hyperuricemia in a clinical aspect (2). Risk factors for hyperuricemia include alcohol consumption, intake of high fat diet and refined carbohydrate, and the medicines of diuretics and angiotensin converting enzyme antagonists (1,2). Population epidemiological studies support the notion that there is a causal link between hyperuricemia and CVD. For example, Rotterdam (3) and a NHANES I study (4) found that there is an association between high levels of UA and myocardial infarctions and cardiovascular death even after adjustment for related factors such as age, dyslipidemia and obesity. Multiple center studies also suggested that hyperuricemia prompts hypertension and coronary heart disease, as well as vascular diseases such as cerebrovascular disease, preeclampsia, vascular dementia and kidney disease (5,6). Some of the potential pathophysiological mechanisms have been investigated to explain the association between UA and vascular injury. One study suggested that high dose UA significantly increased angiotensin II and oxidative stress in cultured endothelial cells (ECs) and this ...

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“…It has been found that the reduction of intestinal excretion of UA [23,24] is an important cause of HUA. Intestinal UA excretion is regulated by urate transporters [25] , such as ABCG2, GLUT9, MRP4 and NPT5. Many studies have demonstrated that ABCG2 [26] is expressed in the gastrointestinal tract at high levels, especially in the intestine, which plays an important role in excreting UA from intestine into feces.…”

Section: Introductionmentioning

confidence: 99%

Dendrobium officinale Six nostrum promotes excretion of intestinal uric acid in hyperuricemia rat through inhibiting LPS/TLR4/NF-κB signaling pathway

Xue¹,

Ge²,

Lei³

et al. 2020

Preprint

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Background : To evaluate the effect of Dendrobium officinale Six nostrum (DOS) on promoting the intestinal excretion of uric acid (UA) in the rat model of hyperuricemia (HUA), and explored its possible mechanisms of action. Methods: In this study, HUA was induced in rat by administration of lipid emulsion (LE) for 6 weeks, meanwhile, the rat was orally administered with DOS for 6 weeks. Then the level of serum uric acid (SUA) and fecal uric acid (FUA) were measured by automatic biochemical analyzer. Lipopolysaccharide (LPS) in hepatic portal vein blood was detected by ELISA kit. The intestinal protein levels of ATP-binding cassette superfamily G member 2 (ABCG2) and glucose transporter 9 (GLUT9) were measured by Western blot assay. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) were determined by immunohistochemistry (IHC). Hematoxylin and eosin (H&E) staining was used to assess intestinal histological changes. Meanwhile, the main compositions of DOS were identified and determined by the High Performance Liquid Chromatography (HPLC). Results: According to HPLC analysis, acteoside and astilbin were identified as the main chemical components of DOS. Our results indicated that DOS significantly reduced SUA level and increased FUA level in the HUA rat induced by oral administration of LE for 6 weeks. IHC and Western blot showed that DOS could significantly increase protein level of ABCG2 and reduce protein level of GLUT9 in the intestine. It remarkably reduced the content of LPS in hepatic portal vein blood and decrease protein levels of TLR4 and NF-κB in the intestine. In addition, DOS could improve the histopathological changes of intestine through increasing the number of intestinal gland goblet cells, and recovering the complete and neatly-arranged structure of small intestinal epithelial cells. Conclusions: DOS has the effect of treating hyperuricemia, the molecular mechanism may be associated with up-regulating ABCG2 protein level, and down-regulating protein level of GLUT9 in the intestine to promote the intestinal excretion of UA, and then decreasing the SUA level. In addition, DOS can reduce the damage of inflammatory response to the intestine, improve the histopathological changes of intestine in HUA rat through inhibiting LPS/TLR4/NF-κB inflammatory pathway.

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Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation

Cited by 42 publications

References 53 publications

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

The role of hyperuricemia on vascular endothelium dysfunction

Dendrobium officinale Six nostrum promotes excretion of intestinal uric acid in hyperuricemia rat through inhibiting LPS/TLR4/NF-κB signaling pathway

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