-
Frontiers in Immunology 2022Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the...
Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated , and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that X11 had excellent UA-lowering activity , which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of to (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA.
Topics: Animals; Gastrointestinal Microbiome; Hyperuricemia; Lacticaseibacillus paracasei; Mice; Mice, Inbred BALB C; Uric Acid
PubMed: 35874662
DOI: 10.3389/fimmu.2022.940228 -
BMC Medicine Jul 2017Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death. The... (Review)
Review
Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death. The frequencies of obesity, chronic kidney disease (CKD), hypertension, type 2 diabetes, dyslipidaemias, cardiac diseases (including coronary heart disease, heart failure and atrial fibrillation), stroke and peripheral arterial disease have been repeatedly shown to be increased in gout. Therefore, the screening and care of these comorbidities as well as of cardiovascular risk factors are of outmost importance in patients with gout. Comorbidities, especially CKD, and drugs prescribed for their treatment, also impact gout management. Numerous epidemiological studies have shown the association of asymptomatic hyperuricaemia with the above-mentioned diseases and cardiovascular risk factors. Animal studies have also produced a mechanistic approach to the vascular toxicity of soluble urate. However, causality remains uncertain because confounders, reverse causality or common etiological factors might explain the epidemiological results. Additionally, these uncertainties remain unsolved despite recent studies using Mendelian randomisation or therapeutic approaches. Thus, large randomised placebo-controlled trials are still needed to assess the benefits of treating asymptomatic hyperuricaemia.
Topics: Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Female; Gout; Humans; Hypertension; Hyperuricemia; Male; Prevalence; Renal Insufficiency, Chronic; Risk Factors
PubMed: 28669352
DOI: 10.1186/s12916-017-0890-9 -
Redox Biology May 2022Serum uric acid (SUA) is significantly elevated in obesity, gout, type 2 diabetes mellitus, and the metabolic syndrome and appears to contribute to the renal,... (Review)
Review
Serum uric acid (SUA) is significantly elevated in obesity, gout, type 2 diabetes mellitus, and the metabolic syndrome and appears to contribute to the renal, cardiovascular and pulmonary comorbidities that are associated with these disorders. Most previous studies have focused on the pathophysiologic effects of high levels of uric acid (hyperuricemia). More recently, research has also shifted to the impact of hypouricemia, with multiple studies showing the potentially damaging effects that can be caused by abnormally low levels of SUA. Along with these observations, recent inconclusive data from human studies evaluating the treatment of hyperuricemia with xanthine oxidoreductase (XOR) inhibitors have added to the debate about the causal role of UA in human disease processes. SUA, which is largely derived from hepatic degradation of purines, appears to exert both systemic pro-inflammatory effects that contribute to disease and protective antioxidant properties. XOR, which catalyzes the terminal two steps of purine degradation, is the major source of both reactive oxygen species (O2, HO) and UA. This review will summarize the evidence that both elevated and low SUA may be risk factors for renal, cardiovascular and pulmonary comorbidities. It will also discuss the mechanisms through which modulation of either XOR activity or SUA may contribute to vascular redox hemostasis. We will address future research studies to better account for the differential effects of high versus low SUA in the hope that this will identify new evidence-based approaches for the management of hyperuricemia.
Topics: Diabetes Mellitus, Type 2; Enzyme Inhibitors; Humans; Hydrogen Peroxide; Hyperuricemia; Uric Acid
PubMed: 35228125
DOI: 10.1016/j.redox.2022.102271 -
Nature Reviews. Rheumatology Feb 2020Asymptomatic hyperuricaemia affects ~20% of the general population in the USA, with variable rates in other countries. Historically, asymptomatic hyperuricaemia was... (Review)
Review
Asymptomatic hyperuricaemia affects ~20% of the general population in the USA, with variable rates in other countries. Historically, asymptomatic hyperuricaemia was considered a benign laboratory finding with little clinical importance in the absence of gout or kidney stones. Yet, increasing evidence suggests that asymptomatic hyperuricaemia can predict the development of hypertension, obesity, diabetes mellitus and chronic kidney disease and might contribute to disease by stimulating inflammation. Although urate has been classically viewed as an antioxidant with beneficial effects, new data suggest that both crystalline and soluble urate activate various pro-inflammatory pathways. This Review summarizes what is known about the role of urate in the inflammatory response. Further research is needed to define the role of asymptomatic hyperuricaemia in these pro-inflammatory pathways.
Topics: Asymptomatic Diseases; Biomarkers; Cytokines; Humans; Hyperuricemia; Immunity, Innate; Uric Acid
PubMed: 31822862
DOI: 10.1038/s41584-019-0334-3 -
International Heart Journal Jul 2016The importance of atrial fibrillation (AF) as a cause of mortality and morbidity has prompted research on its pathogenesis and treatment. Recognition of AF risk factors... (Review)
Review
The importance of atrial fibrillation (AF) as a cause of mortality and morbidity has prompted research on its pathogenesis and treatment. Recognition of AF risk factors is essential to prevent it and reduce the risk of death. Hyperuricemia has been widely accepted to be associated with the incidence of paroxysmal or persistent AF, as well as to the risk of AF in post cardiovascular surgery patients. The possible explanations for this association have been based on their relation with either oxidative stress or inflammation. To investigate the link between hyperuricemia and AF, it is necessary to refer to hyperuricemia-induced atrial remodeling. So far, both ionic channel and structural remodeling caused by hyperuricemia might be plausible explanations for the occurrence of AF. Inhibition of xanthine oxidase and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, or the use of antioxidants, along with serum uric acid (SUA) level reduction to prevent inflammation, might be useful. Uric acid transporters (UATs) play a key role in the regulation of intracellular uric acid concentration. Intracellular rather than serum uric acid level is considered more important for the pathogenesis of AF. Identification of UATs expressed in cells is thus important, and targeting UATs might become a potential strategy to reduce the risk of hyperuricemia-induced atrial fibrillation.
Topics: Antioxidants; Atrial Fibrillation; Atrial Remodeling; Evidence-Based Medicine; Humans; Hyperuricemia; Inflammation; Oxidative Stress; Risk Factors; Uric Acid
PubMed: 27396561
DOI: 10.1536/ihj.16-192 -
Frontiers in Immunology 2022Hyperuricemia has become a common metabolic disease, and is a risk factor for multiple diseases, including chronic kidney disease. Our recent study indicated that...
Hyperuricemia has become a common metabolic disease, and is a risk factor for multiple diseases, including chronic kidney disease. Our recent study indicated that following persistent uric acid stimulation, autophagy was activated in rats of hyperuricemic nephropathy (HN) and facilitated the development of renal fibrosis. Nevertheless, the potential mechanism by which autophagy promoted the progression of HN is still not fully elucidated. Thus, in the current study, we investigated the mechanisms of autophagy inhibition on the development of HN. Our data showed that autophagy was activated in human renal tubular cell lines (HK-2) exposure to uric acid. Inhibition of autophagy with 3-methyladenine (3-MA) and transfected with Beclin-1 siRNA prevented uric acid-induced upregulation of α-SMA, Collagen I and Collagen III in HK-2 cells. Moreover, uric acid upregulated autophagy promoting the p53 pathway. , we showed that hyperuricemic injury induced the activation of NLRP3 inflammasome and pyroptosis, as evidenced by cleavage of caspase-1 and caspase-11, activation of gasdermin D (GSDMD) and the release of IL-1β and IL-18. Treatment with autophagy inhibitor 3-MA alleviated aforementioned phenomenon. Stimulation with uric acid in HK-2 cells also resulted in NLRP3 inflammasome activation and pyroptotic cell death, however treatment with 3-MA prevented all these responses. Mechanistically, we showed that the elevation of autophagy and degradation of autophagolysosomes resulted in the release of cathepsin B (CTSB), which is related to the activation of NLRP3 inflammasome. CTSB siRNA can inhibit the activation of NLRP3 inflammasome and pyroptosis. Collectively, our results indicate that autophagy inhibition protects against HN through inhibiting NLRP3 inflammasome-mediated pyroptosis. What's more, blockade the release of CTSB plays a crucial role in this process. Thus, inhibition of autophagy may be a promising therapeutic strategy for hyperuricemic nephropathy.
Topics: Animals; Autophagy; Caspase 1; Humans; Hyperuricemia; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; RNA, Small Interfering; Rats; Uric Acid
PubMed: 35309342
DOI: 10.3389/fimmu.2022.858494 -
Frontiers in Immunology 2022Periodontitis is one of the most prevalent diseases in oral cavity, which could not merely lead to the destruction of supporting or surrounding tooth structures but also... (Review)
Review
Periodontitis is one of the most prevalent diseases in oral cavity, which could not merely lead to the destruction of supporting or surrounding tooth structures but also affect the whole-body health such as the digestive and nervous systems. Epidemiological investigations suggested that in some developed countries, more than 45% or even 50% population were suffering from periodontitis. However, the prevalence increases with age remarkably and it is investigated that a high prevalence (>50%) is affecting the elderly who is over 65 years old. There is an increasing interest in the direct and indirect relationships between periodontitis and hyperuricemia. Currently, hyperuricemia has become the second major metabolic disease in modern society and the prevalence of hyperuricemia among adult males and females was 21.7% and 14.4% respectively. As an inflammatory disease associated with various systemic diseases, periodontitis may have certain connections with hyperuricemia. Partial existing research announced that hyperuricemia could act as an inhibitory factor for periodontitis, while other scholars presented that a high uric acid (UA) level was more likely to aggravate inflammatory immune response and lead to more serious tissue destruction. This article provides a detailed and comprehensive overview of the relationship underlying hyperuricemia and periodontitis in the molecular mechanisms. Given the impact of hyperuricemia, this review could provide insight into its comorbidities.
Topics: Adult; Aged; Female; Male; Humans; Hyperuricemia; Periodontitis
PubMed: 36466813
DOI: 10.3389/fimmu.2022.995582 -
The American Journal of the Medical... Dec 2020
Topics: Acute Coronary Syndrome; Female; Humans; Hyperuricemia; Male; Mortality; Natriuretic Peptide, Brain; Sex Characteristics
PubMed: 32732079
DOI: 10.1016/j.amjms.2020.07.003 -
Biomedicine & Pharmacotherapy =... Dec 2022Coptisine, one of the main active components of Rhizoma Coptidis, possesses anti-inflammatory, antioxidant, anti-apoptosis and renoprotective effects. In this study, we...
Coptisine, one of the main active components of Rhizoma Coptidis, possesses anti-inflammatory, antioxidant, anti-apoptosis and renoprotective effects. In this study, we investigated the protective effect of coptisine against hyperuricemia induced renal injury in vitro and in vivo, and determined the underlying mechanism. In the in vivo experiment, a mouse model of hyperuricemia induced acute renal injury was established using potassium oxonate (PO)/ hypoxanthine (HX), and in the in vitro experiment, HK-2 cells injury was induced by uric acid (UA). Results showed that coptisine treatment significantly attenuated the acute renal injury via reducing kidney weight and coefficient, UA, creatinine (CRE), blood urea nitrogen (BUN), and histological damages. Meanwhile, coptisine treatment significantly suppressed hyperuricemia induced oxidant stress, inflammatory injury and apoptosis through promoting superoxide dismutase (SOD) activity, restraining reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)- 1β, IL-18 levels, down-regulating protein expressions of cleaved-caspase 3, apoptosis-inducing factor (AIF), cyto-CytC, cleaved poly ADP-ribose polymerase (PARP) and Bcl-2-associated X protein (Bax), and up-regulating protein expressions of Bcl-2 and p-Bad. Additionally, mitochondrial structure damage and ATP depletion in renal tissue and HK-2 cells were observably alleviated. Of note, coptisine treatment remarkably ameliorated hyperuricemia induced phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (PKB/Akt) signaling pathway inhibition. When interference with Akt, the protective effect of coptisine against UA-induced injury in HK2 cells was reversed. All the results suggested that coptisine could protect against hyperuricemia induced renal inflammatory damage, oxidative stress and mitochondrial apoptosis via regulating PI3K/Akt signaling pathway.
Topics: Animals; Mice; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinase; Hyperuricemia; Uric Acid; Phosphatidylinositol 3-Kinases; Signal Transduction; Oxidative Stress; Inflammation; Acute Kidney Injury
PubMed: 36411660
DOI: 10.1016/j.biopha.2022.113941 -
European Heart Journal Sep 2022The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with... (Clinical Trial)
Clinical Trial
BACKGROUND
The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA.
METHODS
The association between SUA and the composite primary outcome of cardiovascular death or hospitalization for worsening HF, its components, and all-cause mortality was investigated in 3676 patients of the EMPEROR-Reduced trial (98.6% of the study cohort). The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricaemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men) and in subgroups of patients of tertiles of SUA.
RESULTS
Hyperuricaemia was prevalent in 53% of patients with no sex differences. Elevated SUA (highest tertile, mean SUA 9.38 ± 1.49 mg/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.64 (95% confidence interval, CI 1.28-2.10); cardiovascular mortality, HR 1.98 (95% CI 1.35-2.91); all-cause mortality, HR 1.8 (95% CI 1.29-2.49), all P < 0.001] in multivariate adjusted analyses, as compared with the lowest tertile. SUA was reduced following treatment with empagliflozin at 4 weeks (vs. placebo: -1.12 ± 0.04 mg/dL, P < 0.0001) and remained lower throughout follow-up, with a similar reduction in all prespecified subgroups. Empagliflozin reduced events of clinically relevant hyperuricaemia (acute gout, gouty arthritis or initiation of anti-gout therapy) by 32% [HR 0.68 (95% CI 0.52-0.89), P = 0.004]. The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA [HR 0.76 (95% CI 0.65-0.88), P < 0.001) and of the change in SUA at 4 weeks [HR 0.81 (95% CI 0.69-0.95), P = 0.012]. As a hypothesis-generating finding, an interaction between SUA and treatment effect suggested a benefit of empagliflozin on mortality (cardiovascular and all-cause mortality) in patients in elevated SUA (P for interaction = 0.005 and = 0.011, respectively).
CONCLUSION
Hyperuricaemia is common in HF and is an independent predictor of advanced disease severity and increased mortality. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricaemia. The benefit of empagliflozin on the primary outcome was observed independently of SUA.
Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Female; Glucose; Glucosides; Heart Failure; Humans; Hyperuricemia; Male; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Uric Acid
PubMed: 35788657
DOI: 10.1093/eurheartj/ehac320