Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis

Existing Reviews

Please note, new claims can take a short while to show up.

No claims yet.

Annotation Summary

Term Occurence Count Dictionary
allopurinol 13 endocrinologydiseasesdrugs
febuxostat 5 endocrinologydiseasesdrugs
glycogen storage disease 1 endocrinologydiseases
hyperglycemia 2 endocrinologydiseases
hyperuricemia 22 endocrinologydiseases
metabolic syndrome 8 endocrinologydiseases
type 2 diabetes mellitus 1 endocrinologydiseases
Insulin 1 endocrinologydiseasesdrugs
diabetes mellitus 2 endocrinologydiseases
hyperlipidemia 2 endocrinologydiseases
hypoglycemia 1 endocrinologydiseases
obesity 4 endocrinologydiseases

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

Review

Having read the paper, please pick a pair of statements from the paper to indicate that a drug and disease are related.

Select Drug Character Offset Drug Term Instance
Insulin 30749 progression have been identified, UA also appears to be a key participant in the onset of NAFLD/NASH.3.3. Insulin Resistance, Diabetes, and HyperlipidemiaHyperuricemia was reportedly found to be related to insulin
allopurinol 10926 from XO might play physiological roles, especially in development. Treatment during pregnancy with allopurinol alters maternal vascular function involving β1-adrenergic stimulation and impairs the fetal α1-adrenergic
allopurinol 19549 hypertension [[96]–[99]]. In a trial targeting prehypertensive obese adolescents, administration of either allopurinol (XO inhibitor) or probenecid (uricosuric agent) lowered blood pressure [[98]]. Consistently, both allopurinol
allopurinol 19659 allopurinol (XO inhibitor) or probenecid (uricosuric agent) lowered blood pressure [[98]]. Consistently, both allopurinol and benziodarone (uricosuric agent) reduced blood pressure in rats with hypertension induced by hyperuricemia
allopurinol 22116 prothrombotic necrotic core by eventually undergoing necrotic or apoptotic death [[116]]. We demonstrated that allopurinol treatment ameliorated aortic lipid accumulation and calcification of the vessels of ApoE-KO mice and
allopurinol 22234 treatment ameliorated aortic lipid accumulation and calcification of the vessels of ApoE-KO mice and that allopurinol markedly suppressed the transformation of J774.1 murine macrophages or primary cultured human macrophages
allopurinol 22929 cholesterol efflux, were decreased by XOR overexpression and increased by XOR knockdown. Furthermore, allopurinol suppressed the expressions of inflammatory cytokines such as IL-1β, IL-6, IL-12, and TNFα, and the
allopurinol 27830 reportedly increased both the intracellular UA concentration and triglyceride (TG) accumulation, while allopurinol , an XO inhibitor, suppressed this fructose-mediated TG deposition. Moreover, the application of UA alone
allopurinol 31312 metabolic syndrome patients, an oxidative stress marker, the myeloperoxidase level, was decreased by allopurinol and endothelial function improved [[159]]. On the other hand, rapid UA reduction achieved by rasburicase,
allopurinol 32463 increased fructose-induced TG accumulation and decreased β-hydroxybutyrate levels, dose-dependently, while allopurinol , a XO inhibitor, blocked it. Because UA is the downstream product of AMPD and allopurinol abolished
allopurinol 32553 dose-dependently, while allopurinol, a XO inhibitor, blocked it. Because UA is the downstream product of AMPD and allopurinol abolished fructose-induced lipid accumulation, AMPD effects on AMPK appeared to depend on UA [[163]].
allopurinol 34287 applications of XO inhibitors to the treatment of various disorders. At present, XO inhibitors, including allopurinol , oxypurinol, febuxostat, and topiroxostat, are widely used for treating gout and hyperuricemia. Furthermore,
allopurinol 36629 and oxidative stress [[176]]. We reported for the first time that more specific XO inhibition, using allopurinol rather than tungsten on macrophages, resulted in the inhibition of foam cell formation and reduced atherosclerotic
allopurinol 36898 the serum lipid profile [[75]]. We also identified phenotypic changes of macrophages in response to allopurinol , such as alterations of gene expressions involved in lipid accumulation. Moreover, both XO overexpression
febuxostat 23190 were upregulated in J774.1 cells transformed into foam cells by atherosclerogenic serum. Subsequently, febuxostat , another XO inhibitor, was also demonstrated to attenuate the development of atherosclerotic lesions
febuxostat 23440 study showed XO expression to be increased in macrophages infiltrating atherosclerotic plaques and that febuxostat diminished the ROS level in the aortic walls of ApoE−/− mice. The authors demonstrated that cholesterol
febuxostat 23866 cytokines such as IL-1α, IL-6, and MCP-1 from macrophages, processes which in turn were suppressed by febuxostat or ROS inhibitors. The significance of NLRP3 inflammasome activation in macrophages by CCs was verified
febuxostat 34312 to the treatment of various disorders. At present, XO inhibitors, including allopurinol, oxypurinol, febuxostat , and topiroxostat, are widely used for treating gout and hyperuricemia. Furthermore, XO inhibitors have
febuxostat 35485 constitute an evolving concept that has yet to be proven. In rats with fructose-induced metabolic syndrome, febuxostat treatment reversed hyperuricemia, hypertension, dyslipidemia, and insulin resistance [[174]]. The beneficial
Select Disease Character Offset Disease Term Instance
diabetes mellitus 16009 involvement of hyperuricemia in CKD is also widely recognized. The major causes of CKD have been regarded as diabetes mellitus and hypertension, and thus, hyperuricemia was long viewed as a consequence of CKD. In fact, loss of
diabetes mellitus 31036 meta-analyses have suggested the UA level to be positively associated with the development of type 2 diabetes mellitus (DM) [[153]–[156]], although Mendelian randomization studies did not support circulating UA as being
glycogen storage disease 14622 fructose metabolism during fatty liver development [[68]]. ATP depletion, such as that characteristic of glycogen storage disease type 1 [[69]], hypoglycemia [[70]], exercise [[71]], and starvation [[72]], also increases UA production.
hyperglycemia 13089 correlation between plasma XO activity and age is observed in both humans and rats [[55]]. It appears that hyperglycemia itself has no impact on liver XO activity, though cardiac, renal, and brain XO activities were shown
hyperglycemia 16374 association between serum UA and the development of CKD. While each metabolic syndrome component, including hyperglycemia , hyperlipidemia, and hypertension, was associated with an increased CKD risk, hyperuricemia was apparently
hyperlipidemia 5693 atherosclerosis and nonalcoholic steatohepatitis (NASH), both of which are associated with insulin resistance, hyperlipidemia , and/or obesity. In this review, atherosclerosis and NASH are discussed extensively, while studies of
hyperlipidemia 16389 serum UA and the development of CKD. While each metabolic syndrome component, including hyperglycemia, hyperlipidemia , and hypertension, was associated with an increased CKD risk, hyperuricemia was apparently an independent
hyperuricemia 1299 However, recently, numerous clinical and basic research approaches have revealed close associations of hyperuricemia with several disorders, particularly those comprising the metabolic syndrome. In this review, we first
hyperuricemia 1892 nonalcoholic steatohepatitis, which were not previously considered to be related, at least not directly, to hyperuricemia . Such beneficial effects of XO inhibitors have been reported for other organs including the kidneys
hyperuricemia 6163 anti-inflammatory effect.2. Inflammation Occurrence Related to UA MetabolismAmong the disorders related to hyperuricemia , gout is the most representative and well known. Features of gout include painful arthritis affecting
hyperuricemia 15712 in various forms of inflammatory or ischemic pathophysiology (Figure 3), not necessarily involving hyperuricemia .3. UA Metabolism and Chronic Renal Disease, Atherosclerosis, Heart Failure, and NASHWhile gout is a
hyperuricemia 15915 gout is a disorder well known to be caused by the precipitation of UA crystals, the involvement of hyperuricemia in CKD is also widely recognized. The major causes of CKD have been regarded as diabetes mellitus and
hyperuricemia 16055 recognized. The major causes of CKD have been regarded as diabetes mellitus and hypertension, and thus, hyperuricemia was long viewed as a consequence of CKD. In fact, loss of kidney function reduces the excretion of UA
hyperuricemia 16196 consequence of CKD. In fact, loss of kidney function reduces the excretion of UA into urine, resulting in hyperuricemia . In contrast, recent studies demonstrated a significant association between serum UA and the development
hyperuricemia 16466 including hyperglycemia, hyperlipidemia, and hypertension, was associated with an increased CKD risk, hyperuricemia was apparently an independent risk factor not influenced by the others. Therefore, hyperuricemia is
hyperuricemia 16563 risk, hyperuricemia was apparently an independent risk factor not influenced by the others. Therefore, hyperuricemia is both a cause and a consequence of CKD and is frequently associated with other metabolic syndrome
hyperuricemia 17185 itself and superoxide free radical generation both play roles in the molecular mechanisms underlying hyperuricemia -related CKD development, but further research is required to elucidate the complex mechanistic interactions
hyperuricemia 18606 diabetes, and CKD as well, which are generally regarded as more established risk factors for CVD than hyperuricemia . Recently, however, a growing body of evidence from both clinical and basic research supports the hypothesis
hyperuricemia 18734 however, a growing body of evidence from both clinical and basic research supports the hypothesis that hyperuricemia , partly via elevated XO activity, is an independent risk factor for hypertension and CVD.Despite the
hyperuricemia 18869 XO activity, is an independent risk factor for hypertension and CVD.Despite the association between hyperuricemia and hypertension having been recognized since the 19th century [[85]], it was not until recently that
hyperuricemia 18985 and hypertension having been recognized since the 19th century [[85]], it was not until recently that hyperuricemia was demonstrated to be an independent risk factor for hypertension development [[87]–[93]]. A recently
hyperuricemia 19767 allopurinol and benziodarone (uricosuric agent) reduced blood pressure in rats with hypertension induced by hyperuricemia [[100], [101]], suggesting that not only XO activity but also UA itself plays an important role in the
hyperuricemia 19956 plays an important role in the pathogenesis of hypertension.Besides the association with hypertension, hyperuricemia or gout has been confirmed to be related to the morbidity and the mortality of CVD [[102]–[106]].
hyperuricemia 20671 case of treating hypertension, uricosuric agents have failed to show any benefits in patients with hyperuricemia or gout [[110], [112]].What are the mechanisms underlying the aforementioned association between hyperuricemia
hyperuricemia 20782 hyperuricemia or gout [[110], [112]].What are the mechanisms underlying the aforementioned association between hyperuricemia and atherosclerotic diseases? First, the role of XO in the pathogenesis of atherosclerosis merits attention.
hyperuricemia 31714 [[160]].Furthermore, excess fructose intake is one of the major causes of the development of obesity with hyperuricemia , fatty liver, and metabolic syndrome. Fructose is metabolized by fructokinase to fructose-1-phosphate
hyperuricemia 34380 including allopurinol, oxypurinol, febuxostat, and topiroxostat, are widely used for treating gout and hyperuricemia . Furthermore, XO inhibitors have been experimentally or clinically shown to exert beneficial effects
hyperuricemia 34628 oxidative stress.Febuxostat preserved renal function in 5/6 nephrectomized rats with and without coexisting hyperuricemia and prevented diabetic renal injury in streptozotocin-treated rats [[166], [167]]. Febuxostat also ameliorated
hyperuricemia 35515 has yet to be proven. In rats with fructose-induced metabolic syndrome, febuxostat treatment reversed hyperuricemia , hypertension, dyslipidemia, and insulin resistance [[174]]. The beneficial effects of XO inhibitors
hypoglycemia 14662 development [[68]]. ATP depletion, such as that characteristic of glycogen storage disease type 1 [[69]], hypoglycemia [[70]], exercise [[71]], and starvation [[72]], also increases UA production. Conditions associated
metabolic syndrome 1371 revealed close associations of hyperuricemia with several disorders, particularly those comprising the metabolic syndrome . In this review, we first outline the two molecular mechanisms underlying inflammation occurrence in
metabolic syndrome 2364 potentially novel strategy for reducing the risk of many forms of organ failure characteristic of the metabolic syndrome .1. IntroductionUric acid (UA) is the end product of the metabolic pathway for purines, the main constituents
metabolic syndrome 4532 close associations of serum UA concentrations and various disorders, most of which are included in the metabolic syndrome category. Thus, UA metabolism may be a so-called double-edged sword as regards the inflammatory and/or
metabolic syndrome 16334 studies demonstrated a significant association between serum UA and the development of CKD. While each metabolic syndrome component, including hyperglycemia, hyperlipidemia, and hypertension, was associated with an increased
metabolic syndrome 16658 Therefore, hyperuricemia is both a cause and a consequence of CKD and is frequently associated with other metabolic syndrome features.In terms of CKD pathogenesis, serum UA is likely to activate the renin-angiotensin system resulting
metabolic syndrome 31211 studies did not support circulating UA as being among the causes of DM development [[157], [158]]. In metabolic syndrome patients, an oxidative stress marker, the myeloperoxidase level, was decreased by allopurinol and endothelial
metabolic syndrome 31746 intake is one of the major causes of the development of obesity with hyperuricemia, fatty liver, and metabolic syndrome . Fructose is metabolized by fructokinase to fructose-1-phosphate and results in a drop in both intracellular
metabolic syndrome 35465 atherosclerosis and NASH constitute an evolving concept that has yet to be proven. In rats with fructose-induced metabolic syndrome , febuxostat treatment reversed hyperuricemia, hypertension, dyslipidemia, and insulin resistance [[174]].
obesity 5716 steatohepatitis (NASH), both of which are associated with insulin resistance, hyperlipidemia, and/or obesity . In this review, atherosclerosis and NASH are discussed extensively, while studies of gout and chronic
obesity 27099 increased in murine NAFLD/NASH models [[133], [134]]. Moreover, a fraction of NAFLD/NASH patients also have obesity , and hypertrophic adipocytes were also reported to secrete UA [[135]]. Taken together, these results
obesity 31701 sensitivity [[160]].Furthermore, excess fructose intake is one of the major causes of the development of obesity with hyperuricemia, fatty liver, and metabolic syndrome. Fructose is metabolized by fructokinase to
obesity 35732 NASH are rarely reported, except by our research group [[134]], because animal models of NASH with obesity , inflammation, and fibrosis have been difficult to establish. NASH in response to the MCD diet, as used
type 2 diabetes mellitus 31029 several meta-analyses have suggested the UA level to be positively associated with the development of type 2 diabetes mellitus (DM) [[153]–[156]], although Mendelian randomization studies did not support circulating UA as being

You must be authorized to submit a review.