Reduced Serum Uric Acid Research Articles

Uric Acid as a Biomarker for Mood Disorders: A Comparative Study of Blood Uric Acid Levels Correlating With the Symptom Severity and Treatment Response.

Background Bipolar affective disorder (BPAD) and major depressive disorder (MDD) are two mood disorders whose pathophysiology may involve the purinergic system. Elevated uric acid levels, associated with this system, can impact various behaviors in individuals affected by these conditions. In addition to genetic predisposition, blood uric acid levels can be impacted by various factors, including metabolic syndrome, the consumption of psychoactive medications, and other underlying kidney conditions such as gout. Objective The study aims to investigate the relationship between blood uric acid levels and mental health conditions, specifically BPAD subtypes (manic and depressive) and MDD. The study also examines changes in blood uric acid levels following treatment and evaluates the effectiveness of different treatment approaches in reducing uric acid levels. Methodology To be eligible to participate, individuals must have a confirmed diagnosis of BPAD (manic or depressive type) or MDD, according to the International Classification of Diseases (ICD-10). Blood uric acid levels were measured at both baseline and follow-up assessments. Symptoms were assessed weekly using standardized rating scales (Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAM-D)) until treatment response was achieved, which was defined as a 50% reduction in initial scores on both scales. We used ANOVA to examine the differences among the three patient groups and paired sample t-tests to examine the changes in means before and after treatment conditions. Results A significant positive correlation was found between the severity of illness and serum uric acid levels across all three patient groups: those with BPAD-mania, BPAD-depression, and MDD. Notably, patients with BPAD-mania patients had significantly higher serum uric acid levels (5.2±0.9 mg/dL) compared to those with BPAD-depression (4.8±1.0 mg/dL) and MDD (4.0±1.1 mg/dL). After treatment, all patient groups exhibited a decrease in serum uric acid levels. The reduction in serum uric acid levels was pronounced in all patient groups, with decreases of 3.1±0.8 mg/dL in patients with BPAD-mania, 3.1±0.9 mg/dL in those with BPAD-depression, and 3.5±1.1 mg/dL in those with MDD. The study showed that the reduction in serum uric acid levels was significantly correlated with the severity of illness in patients with BPAD-mania, but not in those with BPAD-depression or MDD. Furthermore, the study found that treatment with lithium carbonate, sodium valproate, or carbamazepine was equally effective in reducing serum uric acid levels, regardless of the mood stabilizer used. Conclusion The study supports that dysfunction in the purine system might play a significant role in the development and progression of BPAD, suggesting that this phenomenon is not solely due to chronicity or medication exposure. This study also introduces a fresh perspective on the underlying biological processes that contribute to the development of BPAD and also sheds light on new treatment regimens targeting uric acid reduction in treating patients with bipolar disorder.

The SGLT2 inhibitor dapagliflozin ameliorates renal fibrosis in hyperuricemic nephropathy

Hyperuricemic nephropathy (HN) is a global metabolic disorder characterized by uric acid (UA) metabolism dysfunction, resulting in hyperuricemia (HUA) and tubulointerstitial fibrosis (TIF). Sodium-dependent glucose transporter 2 inhibitor, dapagliflozin, has shown potential in reducing serum UA levels in patients with chronic kidney disease (CKD), though its protective effects against HN remain uncertain. This study investigates the functional, pathological, and molecular changes in HN through histological, biochemical, and transcriptomic analyses in patients, HN mice, and UA-stimulated HK-2 cells. Findings indicate UA-induced tubular dysfunction and fibrotic activation, which dapagliflozin significantly mitigates. Transcriptomic analysis identifies estrogen-related receptor α (ERRα), a downregulated transcription factor in HN. ERRα knockin mice and ERRα-overexpressed HK-2 cells demonstrate UA resistance, while ERRα inhibition exacerbates UA effects. Dapagliflozin targets ERRα, activating the ERRα-organic anion transporter 1 (OAT1) axis to enhance UA excretion and reduce TIF. Furthermore, dapagliflozin ameliorates renal fibrosis in non-HN CKD models, underscoring the therapeutic significance of the ERRα-OAT1 axis in HN and CKD.

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Assessment of oral toxicity of Moringa oleifera Lam aqueous extract and its effect on gout induced in a murine model.

Although widely employed in traditional remedies globally, the safety and efficacy of Moringa oleifera remain inadequately documented through scientific research. This study evaluated the oral toxicity of M. oleifera leaf aqueous extract (MoAE) and its impact on gout-induced rats. 2000 mg/kg was given in a single dose during the acute oral toxicity test, while 100 mg/kg, 250 mg/kg, and 500 mg/kg were given daily for 28 days in the repeated dose toxicity test. 100 mg/kg, 250 mg/kg, and 500 mg/kg MoAE doses were administered during the assessment of its impact on gout caused by monosodium urate. In the hyperuricemia model induced by oxonic acid, serum uric acid levels were assessed and pain response was measured through acetic acid-induced writhing. In acute oral and 28-day repeated dose tests, no indications of toxicity were detected, while MoAE alleviated ankle joint swelling and reduced serum uric acid concentrations in arthritic rats, causing a significant reduction in acetic acid-induced contortions. No acute oral toxicity or toxicity in 28-day repeated doses was found for MoAE, while it exhibited antiarthritic, antihyperuricemic, and pain-relieving effects in the murine model.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 μmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 μmol/L) compared with placebo (95%CI: -1.5 to -0.9; P &lt; 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P &lt; 0.001), NT-proBNP by 25% (95%CI: 18-32; P &lt; 0.001), and QoL scores by 10 points (95%CI: 7-13; P &lt; 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15–50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Simiao pills alleviates renal injury associated with hyperuricemia: A multi-omics analysis

Ethnopharmacological relevanceSimiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du, has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism. Aim of the studyThis study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action. Materials and methodsUPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms. ResultsSimiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1β signaling pathway. ConclusionThis study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients.

Antigout effects and mechanisms of total flavonoids from prunus tomentosa.

In recent years, hyperuricemia and acute gouty arthritis have become increasingly common, posing a serious threat to public health. Current treatments primarily involve Western medicines with associated toxic side effects. This study aims to investigate the therapeutic effects of total flavones from Prunus tomentosa (PTTF) on a rat model of gout and explore the mechanism of PTTF's anti-gout action through the TLR4/NF-κB signaling pathway. We measured serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA). Histopathological changes were observed using HE staining, and the expression levels of relevant proteins were detected through Western blotting. After PTTF treatment, all indicators improved significantly. PTTF reduced blood levels of UA, Cr, BUN, IL-1β, IL-6, and TNF-α, and decreased ankle swelling. PTTF may have a therapeutic effect on animal models of hyperuricemia and acute gouty arthritis by reducing serum UA levels, improving ankle swelling, and inhibiting inflammation. The primary mechanism involves the regulation of the TLR4/NF-κB signaling pathway to alleviate inflammation. Further research is needed to explore deeper mechanisms.

#1116 Hyperuricemia worsens bacterial sepsis by suppressing neutrophil functions in CKD

Abstract Background and Aims Patients with kidney disease, especially those on dialysis, are more susceptible to infections such as peritonitis, sepsis, pneumonia, and are at a higher risk for infection-related mortality. Pathogenic mechanisms underlying the secondary immunodeficiency in kidney disease include gut dysbiosis and barrier dysfunction, persistent inflammation, immune paralysis due to increased levels of immunoregulatory metabolites (e.g. uric acid) and proteins (e.g. FGF23) [1]. Currently, it is unknown whether CKD-related hyperuricemia may contribute to the immune paralysis in this context. We hypothesized that hyperuricemia (HU) may aggravate the innate immune response to infection in CKD in mice. Method Mono- and polybacterial sepsis was induced by LPS injection or cecal ligation and puncture in Alb-creERT2;Glut9lox/lox mice with HU and/or CKD, and in Glut9lox/lox (healthy) control mice. After 24 hours, systemic inflammation was evaluated by measuring serum cytokine levels, immune cell activation and recruitment, and neutrophil extracellular trap release. Tissue injury in liver, heart, and kidney was assessed by performing RT-qPCR and immunohistochemistry. In addition, kidney function was determined by measuring the glomerular filtration rate (GFR). Additionally, mice were treated with urate-lowering therapy to reduce serum uric acid levels and the immune response and functional outcomes after sepsis is quantified. Results We found that both mono- and polybacterial sepsis caused systemic inflammation as indicated by an increased number of blood neutrophils (see Figure), neutrophil activation and pro-inflammatory cytokine levels as compared to the PBS-treated or sham-operated control groups in Glut9lox/lox healthy mice, respectively. Mice with sepsis also displayed a slightly worsened kidney function. Interestingly, HU significantly increased neutrophil numbers but decreased their activation status and the ability of neutrophils to form neutrophil extracellular traps in Alb-creERT2;Glut9lox/lox mice with sepsis as compared to the control groups, which was further aggravated in mice with CKD-related HU (CKD+HU). This impaired inflammatory response was partially reversible by lowering serum uric acid with febuxostat. Conclusion Our results identify hyperuricemia related or unrelated to kidney disease as immune regulator in bacterial infection by suppressing neutrophil functions in mice. Specifically targeting uric acid may help to overcome the secondary immunodeficiency related to kidney disease during infection but enhances sterile inflammation [2].

Effects of Smilax China L. extracts on Hyperuricemia chicken model via inhibiting xanthine oxidase activity

Hyperuricemia (HUA) is a metabolic disorder caused by excessive production of uric acid (UA) or impaired uric acid metabolism. Smilax China L. has a wide range of pharmacological activities such as immunomodulatory, anti-inflammatory, and antioxidant. Its roots and rhizomes have been widely used for the treatment of HUA. However, its mechanisms for treating HUA and reducing renal impairment have not been fully elucidated. In the present study, we evaluated the effect of Smilax China L. extract (SC) on UA metabolism and further explored its mechanism of action by feeding a high-calcium and high-protein diet to chickens to induce a model of HUA in chickens. SC significantly reduced serum UA levels and improved renal function in hyperuricemic chickens. Meanwhile, SC was able to inhibit the activity of xanthine oxidase (XOD) in vivo and in vitro, reducing the production of uric acid. In addition, SC was able to increase the expression of Breast Cancer Resistance Protein (BCRP) in the kidney and ileum and increase uric acid excretion. Therefore, our results suggest that SC may be a candidate for anti-hyperuricemia.

Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota

Ethnopharmacological relevanceIn ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. Aim of the studyTo determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. Materials and methodsPotassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1β) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. ResultsIn this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1β. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. ConclusionRGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.

Identification of Hyperuricemia Alleviating Peptides from Yellow Tuna Thunnus albacares.

The development of food-derived antihyperuricemic substances is important for alleviating hyperuricemia (HUA) and associated inflammation. Here, novel peptides fromThunnus albacares (TAP) with strong antihyperuricemic activity were prepared. TAP was prepared by alkaline protease (molecular weight <1000 Da), with an IC50 value of xanthine oxidase inhibitory activity of 2.498 mg/mL, and 5 mg/mL TAP could reduce uric acid (UA) by 33.62% in human kidney-2 (HK-2) cells (P < 0.01). Mice were fed a high-purine diet and injected with potassium oxonate to induce HUA. Oral administration of TAP (600 mg/kg/d) reduced serum UA significantly by 42.22% and increased urine UA by 79.02% (P < 0.01) via regulating urate transporters GLUT9, organic anion transporter 1, and ATP-binding cassette subfamily G2. Meantime, TAP exhibited hepatoprotective and nephroprotective effects, according to histological analysis. Besides, HUA mice treated with TAP showed anti-inflammatory activity by decreasing the levels of toll-like receptor 4, nuclear factors-κB p65, NLRP3, ASC, and Caspase-1 in the kidneys (P < 0.01). According to serum non-targeted metabolomics, 91 differential metabolites between the MC and TAP groups were identified, and purine metabolism was considered to be the main pathway for TAP alleviating HUA. In a word, TAP exhibited strong antihyperuricemic activity both in vitro and in vivo.

Treatment of Hyperuricemia with Thlaspi Bursa Pastoris 6CH: A Randomized, Open-Label, Equivalence Trial

Abstract Background: Hyperuricemia (HU) remains a priority research area in every medical science, including complementary and alternative medicine interventions and homeopathy; however, the research evidence is limited. In homeopathy, Thlaspi bursa pastoris (TBP) is considered to be a potential treatment option in HU. Methods: An open-label, randomized, equivalence trial was conducted comparing TBP with individualized homeopathic medicines (IHMs). Serum uric acid (SUA) was the primary outcome; Gout Assessment Questionnaire version 2.0 (GAQ-2) and Measure Yourself Medical Outcome Profile version 2.0 (MYMOP-2) were the secondary outcomes; all measured at baseline and after 6 and 12 weeks. Intention-to-treat analysis was carried out to detect noninferiority and group differences using unpaired t-tests and two-way repeated-measure analysis of variance (ANOVA). Results: There were no differences between the groups at baseline. Reduction in SUA after 6 and 12 weeks was similar between groups (P = 0.784). Group differences in the secondary outcomes were also nonsignificant (all P &gt; 0.05). TBP revealed noninferiority against IHMs, both after 6 weeks and 12 weeks in SUA and MYMOP-2 profile scores, but not in GAQ2 scores. Sulfur and Calcarea carbonica were the most frequently prescribed medicines in the IHMs group. There were no harms or serious adverse events reported from either of the groups. Conclusion: TBP acted noninferior to IHM in HU and both appeared to be equally effective. Rigorous and larger trials are warranted. Trial Registration: This trial was registered in the Clinical Trials Registry – India (CTRI/2018/10/016174; UTN: U1111-1221-8000).

EFFECTS OF ALLISARTAN ON URIC ACID, LEFT ATRIAL, LEFT VENTRICULAR AND ARTERY STIFFNESS IN MILD-TO-MODERATE ESSENTIAL HYPERTENSION

Objective: Our study aimed to explore the effects of allisartan on blood pressure, uric acid (UA), left atrial, left ventricular structure and function and artery stiffness in mild-to-moderate essential hypertension. Design and method: Our study is a randomised, double-blind, crossover design involving 98 patients with mild-to-moderate essential hypertension. Participants were administered allisartan (240mg) or olmesartan (20mg) once daily for 12 weeks each in varying sequences. Results: Both allisartan and olmesartan led to a significant decrease in systolic blood pressure (SBP) levels from baseline, with no significant difference between the two drugs (δ= 6.5mmHg, P&lt;0.001 and δ= 5.64mmHg, P=0.002). Notably, allisartan exhibited a more pronounced reduction in diastolic blood pressure compared to olmesartan (δ= 3.66mmHg, P=0.001), with superior efficacy in lowering diastolic blood pressure (DBP) (δ= 3.39mmHg, P=0.016). Allisartan significantly dropped serum UA levels (δ= 26.37 μmol/L, P&lt;0.001), whereas olmesartan did not achieve a significant reduction compared to allisartan (δ= 33.63 μmol/L, P&lt;0.001). In terms of cardiac and artery stiffness, allisartan demonstrated significant reductions in left atrial volume index (LAVI) (δ= 2.86 ml/m2, P&lt;0.001), left ventricular mass index (LVMI) (δ= 4.82 g/m2, P=0.010) and ankle-brachial pulse wave velocity (baPWV) (δ= 154.49 cm/s, P&lt;0.001), all-surpassing olmesartan significantly (all P&lt;0.01). Conclusions: In conclusion, compared to olmesartan, allisartan demonstrates significant reductions in serum UA, blood pressure, LAVI, LVMI and baPWV in patients with mild to moderate essential hypertension. This study provides new evidence supporting the efficacy of allisartan in treating mild-to-moderate essential hypertension and reducing serum UA levels in this population.

Preventive effect of Lactobacillus johnsonii YH1136 against uric acid accumulation and renal damages.

Hyperuricemia (HUA) is a prevalent metabolic disorder whose development is associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, the underlying mechanisms of many effective probiotic strains remain unknown. C57BL/6 mice were randomly divided into two groups: control and model groups. The model group received 12 weeks of potassium oxonate. Through 16s sequencing we found that HUA resulted in a significant decrease in the total diversity of all intestinal segments. When each intestinal segment was analyzed individually, the reduction in diversity was only significant in the cecum and colon sections. RDA analysis showed that lactobacilli in the rat colon exhibited a strong correlation with model group, suggesting that Lactobacillus may play an important role in HUA. Consequently, the preventive effects of Lactobacillus johnsonii YH1136 against HUA were investigated. C57BL/6 mice were randomly divided into three groups: control, model and YH1136 groups. The results showed that administering Lactobacillus johnsonii YH1136 effectively reduced serum UA levels in vivo by inhibiting hepatic xanthine oxidase (XOD) activity and promoting renal ABCG2 transporter expression. Moreover, supplementation with Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, thereby reducing UA accumulation. Hyperuricemia is accompanied by an altered composition of multiple gut bacteria, of which Lactobacillus is a key genus. Lactobacillus johnsonii YH1136 may ameliorate renal involvement in HUA via the gut-kidney axis.

Protecting against ferroptosis in hyperuricemic nephropathy: The potential of ferrostatin-1 and its inhibitory effect on URAT1

Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro. Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC50 value of 7.37 ± 0.66 μM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.

Development and characterization of liposomal formulations containing sesquiterpene lactones for the treatment of chronic gout

Gout and hyperuricemia are characterized by high uric acid levels, and their treatment involves medications that have adverse effects. In this study, we evaluated oral liposomal formulations with eremantholide C and goyazensolide as a novel approach to reduce the toxicity associated with these substances while maintaining their anti-hyperuricemic activity. We characterized the formulations and evaluated them based on encapsulation efficiency and stability over 12 months and under simulated physiological environments. We determined the toxicity of the liposomal formulations in Caco-2 cells and the anti-hyperuricemic activity in rats. The formulations exhibited nanometric size, a narrow size distribution, and a negative zeta potential, indicating their stability and uniformity. The efficient encapsulation of the sesquiterpene lactones within the liposomes emphasizes their potential for sustained release and therapeutic efficacy. Stability evaluation revealed a small decrease in the eremantholide C concentration and a remarkable stability in the goyazensolide concentration. In Caco-2 cells, the liposomes did not exert toxicity, but did exhibit an antiproliferative effect. In vivo assays demonstrated that the liposomes reduced serum uric acid levels. Our study represents an advancement in gout and hyperuricemia treatment. The liposomal formulations effectively reduced the toxicity associated with the sesquiterpene lactones while maintaining their therapeutic effects.

Pharmacological inhibition of Src family kinases attenuates hyperuricemic nephropathy.

Hyperuricemia is an independent risk factor for chronic kidney disease and contributes to renal fibrosis. This study aims to investigate the effect of Src family kinase (SFK) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN, feeding rats a mixture of adenine and potassium oxonate increased Src phosphorylation, severe glomerular sclerosis, and renal interstitial fibrosis, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of PP1, a highly selective SFK inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. PP1 treatment also inhibited hyperuricemia-induced activation of the TGF-β1/Smad3, STAT3, ERK1/2, and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, PP1 treatment significantly reduced serum uric acid levels and xanthine oxidase activity. Thus, blocking Src can attenuate development of HN via a mechanism associated with the suppression of TGF-β1 signaling, inflammation, and uric acid production. The results suggest that Src inhibition might be a promising therapeutic strategy for HN.

Piperine Improves Hyperuricemic Nephropathy by Inhibiting URAT1/GLUT9 and the AKT-mTOR Pathway.

Uncontrolled hyperuricemia often leads to the development of hyperuricemic nephropathy (HN), characterized by excessive inflammation and oxidative stress. Piperine, a cinnamic acid alkaloid, possesses various pharmacological activities, such as antioxidant and anti-inflammatory effects. In this study, we intended to investigate the protective effects of piperine on adenine and potassium oxonate-induced HN mice and a uric-acid-induced injury model in renal tubular epithelial cells (mRTECs). We observed that treatment with piperine for 3 weeks significantly reduced serum uric acid levels and reversed kidney function impairment in mice with HN. Piperine (5 μM) alleviated uric acid-induced damage in mRTECs. Moreover, piperine inhibited transporter expression and dose-dependently inhibited the activity of both transporters. The results revealed that piperine regulated the AKT/mTOR signaling pathway both in vivo and in vitro. Overall, piperine inhibits URAT1/GLUT9 and ameliorates HN by inhibiting the AKT/mTOR pathway, making it a promising candidate for patients with HN.

Gout: physical activity in therapy and prevention of the disease

Gout is a systemic chronic inflammatory disease associated with purine metabolism disorders. Risk factors for gout are a combination of genetic and environmental factors. Taking into account such features of the pathogenesis of gout as hyperuricemia and the deposition of monosodium urate crystals in tissues and joints, the development of the inflammatory, researchers studied the effect of physical activity on its main links. The intensity of the load and the type of physical exercise were taken into account due to their possible effect on metabolic processes. There is currently no reliable evidence on the importance of physical activity in reducing serum uric acid levels. Research has shown that physical activity has a positive effect on inflammation between gout attacks. The use of physical exercise can indirectly affect uric acid levels by reducing body weight in comorbid pathologies. EULAR emphasizes physical activity to prevent cardiovascular risks, which is also important for gout. Conclusions. Physical activity as one of the components of lifestyle is important for gout due to its effect on the inflammatory process and the prevention of relapses, a general strengthening effect on the body, an effect on hyperuricemia due to the positive effect associated with comorbid pathology, and a decrease in cardiovascular risk and associated him premature death. Physical activity of low and moderate intensity is effective for gout. Preference is given to aerobic exercise, taking into account the nature of metabolism and the possible impact on the occurrence of gout attacks. Further study and development of the characteristics of physical activity in gout are necessary to improve the prevention and treatment of the disease, and the development of individual recommendations for patients (for the management of gout).

Clinical study to Evaluate Safety and Efficacy of Boozidaan (Pyrethrum indicum) in the management of Niqris Muzmin (Chronic Gout)

Objectives: The objectives of this study were to observe the Efficacy of unani pharmacopoeial formulation Boozidan (Pyrethrum indicum) for the management of Niqris Muzmin (Chronic gout) and to observe any concomitant and adverse effects of formulation.&#x0D; Methods: This single blind, randomized and standard control clinical study was conducted between April 2021 to October 2021 for a period of 28 days. 60 patients diagnosed with chronic gout were divided into two groups, 30 Test group and 30 Control group. The test group was administered with 5g boozidaan in powder form once daily with water and the patients of control group were given tablet febuxostat 80mg once daily. Patients were followed up and improvements in subjective parameters were assessed weekly at 7th, 14th, 21st, and 29th day. Objective parameters were assessed at the baseline and at 29th day. The data obtained was subjected to statistical analysis.&#x0D; Results: Both the test and control drug were effective in reducing Serum uric acid level, ESR and CRP levels. A significant improvement in subjective and objective parameters was observed in both test and control groups and no adverse effects were observed during and after the study.&#x0D; However, the test drug had superior efficacy in reducing the objective parameters and it was statistically significant (p-value&lt;0.0001).&#x0D; Conclusion: Both Boozidaan and Febuxostat were safe and significantly effective in resolving the symptoms and signs of gouty arthritis and both have significant effect on reducing serum uric acid level.&#x0D; Keywords: Boozidaan, Chronic gout, Niqris, Febuxostat, serum uric acid, unani medicine