Elevated Uric Acid Levels Research Articles

Anti-inflammatory and Anti-hyperuricemic Effect of Ficus benghalensis Bark Extract in Raw 246.7 Cell Line

Abstract: Background: Hyperuricemia and inflammation are associated with the etiology and pathogenesis of several metabolic diseases. Controlling the elevated levels of uric acid and inflammation can be a potential therapeutic option for several metabolic diseases. Aim: The current study examined the anti-inflammatory and anti-hyperuricemic properties of Ficus benghalensis bark extract in vitro using murine macrophage RAW 246.7 cells. Materials and Methods: Hydroalcoholic extracts of Ficus benghalensis bark were obtained. Cytotoxicity and cell viability test of the extracts was evaluated by MTT and Trypan blue exclusion assay. Cells were microscopically observed for the presence of dead cells. To explore the anti-inflammatory and anti-hyperuricemic activity, RAW 246.7 cells were induced with lipopolysaccharide and treated at the concentrations of 20, 40, and 60 μg/ml of Ficus benghalensis bark extract and assessed for xanthine oxidase activity, uric acid levels, reactive oxygen species, lipid peroxidation assay, nitric oxide levels and gene expression studies of a pro-inflammatory and anti-inflammatory cytokine such as TNF-α and IL- 10. Results: A dose-dependent reduction in the xanthine oxidase activity when treated with the bark extract with higher inhibition at 60 μg/ml. Reduction in the amount of uric acid, ROS, nitric oxide, and lipid peroxidation are similar to xanthine oxidase activity with a significant decrease in all treated groups and higher reduction at 60 μg/ ml treatment. Gene expression study showed downregulation of TNF-α and upregulation of IL- 10 in treated groups. Conclusion: Our study demonstrates that Ficus benghalensis bark extract exhibits anti-hyperuricemic and anti-inflammatory effects possibly through xanthine oxidase inhibition. The results provide evidence that Ficus benghalensis bark extract may have the potential to treat hyperuricemia and complications related to hyperuricemia. Keywords: Anti-hyperuricemic, RAW 246.7 cells, Ficus benghalensis bark extract, Antiinflammatory, TNF-α, IL- 10, Lipopolysaccharide.

Testing the Institute of Medicine (IOM) recommendations on maternal reproductive health and associated neonatal characteristics in a transitional, Mediterranean population

Background High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health. Aim To assess pre-pregnancy BMI and GWG during pregnancy and their association with different maternal and neonatal characteristics in the transitional Mediterranean population from the Eastern Adriatic islands. Subjects and methods Two hundred and sixty-two mother–child dyads from the CRoatian Islands’ Birth Cohort Study (CRIBS) were included in the study. Chi-square test, ANOVA, and regression analysis were used to test the association between selected characteristics. Results In total, 22% of women entered pregnancy as overweight/obese and 46.6% had excessive GWG. Pre-pregnancy overweight and obesity were significantly associated with elevated triglycerides uric acid levels, and decreased HDL cholesterol in pregnancy. Excessive GWG was associated with elevated fibrinogen and lipoprotein A levels. Women with high pre-pregnancy BMI and GWG values were more likely to give birth to babies that were large for gestational age (LGA), additionally confirmed in the multiple logistic regression model. Conclusion High maternal pre-pregnancy BMI and excessive GWG were both significantly associated with deviated biochemical parameters and neonatal size. More careful monitoring of maternal nutritional status can lead to better pre- and perinatal maternal healthcare.

Autophagy protects against high uric acid-induced hepatic insulin resistance

Uric acid (UA), the end-product of purine metabolism, is closely related to hepatic insulin resistance (IR). Autophagy is a conserved intracellular degradation process maintaining cellular homeostasis. Autophagy plays a protective role in obesity-related hepatic IR, but whether it occurs in high uric acid (HUA)-induced hepatic IR is unclear. In this study, spontaneously elevated UA level induced hepatic IR and facilitated hepatic autophagy degradation in uricase knockout (Uox-/-) mice. In vitro, HepG2 cells stimulated with HUA medium showed decreased glucose uptake and inhibition of insulin signaling pathways, concomitant with activation of autophagy, as manifested by increased conversion of LC3B–I to –II. Rapamycin, the autophagy activator, alleviated but the autophagy inhibitor trimethyl adenine (3-MA) aggravated HUA-induced IR in HepG2 cells. Similarly, rapamycin ameliorated and 3-MA worsened HUA-induced blood glucose level and hepatic IR in Uox-/- mice. Mechanistically, HUA enhanced AMPKα phosphorylation (p-AMPKα) and inhibited mammalian target of rapamycin phosphorylation (p-mTOR) in HepG2 cells. The levels of p-AMPKα and LC3B-II/I were downregulated in HepG2 cells transfected with small interfering RNA (siRNA) against AMPKα, which suggests that the AMPKα–mTOR pathway was involved in HUA-induced autophagy. Antioxidant N-acetyl-L-cysteine reversed elevated reactive oxygen species levels induced by HUA in HepG2 cells, and AMPKα level was also inhibited, which suggests that AMPKα activation may be derived from reactive oxygen species. Collectively, these findings demonstrate that HUA increased hepatic autophagy, and autophagy activation plays a protective role in hepatic IR, which may suggest a potential therapeutic target for hepatic IR derived from HUA.

Interactions between nocturnal melatonin secretion, metabolism, and sleeping behavior in adolescents with obesity

Background/objectivesSleeping behavior and individual prospensity in sleep timing during a 24 h period, known as chronotypes, are underestimated factors, which may favor the development of obesity and metabolic diseases. Furthermore, melatonin is known to play an important role in circadian rhythm, but was also suggested to directly influence metabolism and bodyweight regulation. Since disturbed and shifted sleep rhythms have been observed in adolescents with obesity, this study aimed to investigate potential interactions between melatonin secretion, chronobiology, and metabolism. In addition, the influence of artificial light especially emitted by electronic devices on these parameters was of further interest.Subjects/methodsWe performed a cross-sectional study including 149 adolescents (mean age 14.7 ± 2.1 years) with obesity. Metabolic blood parameters (e.g., cholesterol, triglycerides, uric acid, and insulin) were obtained from patients and correlated with nocturnal melatonin secretion. Melatonin secretion was determined by measuring 6-sulfatoxymelatonin (MT6s), the major metabolite of melatonin in the first-morning urine, and normalized to urinary creatinine levels to account for the urinary concentration. Chronobiologic parameters were further assessed using the Munich ChronoType Questionnaire.ResultsSubjects with insulin resistance (n = 101) showed significantly lower nocturnal melatonin levels compared to those with unimpaired insulin secretion (p = 0.006). Furthermore, triglyceride (p = 0.012) and elevated uric acid levels (p = 0.029) showed significant associations with melatonin secretion. Patients with late chronotype showed a higher incidence of insulin resistance (p = 0.018). Moreover, late chronotype and social jetlag were associated with the time and duration of media consumption.ConclusionWe identified an association of impaired energy metabolism and lower nocturnal melatonin secretion in addition to late chronotype and increased social jetlag (misalignment of biological and social clocks) in adolescents with obesity. This might point towards a crucial role of chronotype and melatonin secretion as risk factors for the development of pediatric and adolescent obesity.

Pyrazinamide-induced Polyarthralgia and Myalgia in a Case of Stable Chronic Kidney Disease

Abstract: Pyrazinamide is known to cause hyperuricemia and is followed by gout arthritis. But the fate of this drug in chronic kidney disease (CKD) patients is still not explored in details yet. We report a case of a 65-year-old Asian-Indian woman who was diagnosed with stable CKD 5 years ago and is currently diagnosed with peritoneal tuberculosis with pleural effusion. She was started on antitubercular therapy (ATT). On the 11th day of ATT, she developed a rise in uric acid (from 7.2 mg/dL to 13.1 mg/dL) and creatine kinase levels (from 156 U/L to 887 U/L), followed by polyarthralgia and generalised myalgia on investigation. Her elevated uric acid and creatine kinase levels and polyarthralgia improved on cessation of pyrazinamide, but improvement in her myalgia and muscle weakness was postponed. Pyrazinamide plasma 2 hr levels post dose was performed suspecting polyarthralgia and myalgia as an adverse drug reaction and estimated to be 59 μg/ml (normal range: 20-50 μg/ml). Subjective and objective assessments along with pyrazinamide plasma levels may be an indicative evidence of the adverse reaction as the estimated plasma concentration at 2 hr was higher than the normal range. Key words: Pyrazinamide, Polyarthralgia, Myalgia, Stable chronic kidney disease, Plasma levels.

Anopheles gambiae Actively Metabolizes Uric Acid Following Plasmodium Infection to Limit Malaria Parasite Survival.

Characterizing the physiological changes that accompany malaria parasite infection of the mosquito host is crucial to our understanding of vectorial capacity in Anopheles mosquitoes, yet has not fully been explored. In this study, we examine the role of uric acid metabolism in the mosquito, Anopheles gambiae, following malaria parasite infection. We demonstrate that levels of uric acid are significantly decreased in the excreta and the mosquito at 24 and 48 h post-Plasmodium infection when compared to controls fed on naïve mouse blood. When we examine the expression of well-known enzymes responsible for uric acid metabolism, we see a significant increase in both urate oxidase (UO) and allatoicase (ALLC) expression following Plasmodium infection. Targeting the essential first step in uric acid metabolism by silencing UO resulted in elevated levels of uric acid, enhancing malaria parasite survival. With implications from other insect systems that bacteria can modulate UO expression, we examined the possibility that the mosquito microbiota and its expansion following blood-feeding may contribute to increased UO levels. However, there was no difference in uric acid metabolism between septic and aseptic mosquitoes, indicating that the mosquito microbiome is not associated with the manipulation of UO expression. Together, our study provides new evidence that Plasmodium infection causes the mosquito host to actively metabolize uric acid by increasing UO expression to limit Plasmodium oocyst survival, suggesting that nitrogen metabolism is an essential pathway in defining mosquito vector competence.

Sida acuta leaf extract attenuates oxidants-induced animal model of nephrotoxicity and hepatotoxicity

BackgroundCurative potential of Sida acuta Burm. f. (Malvaceae) leaves on hepatotoxicity and nephrotoxicity induced by carbon tetrachloride (CCl4) and rifampicin was studied. This was aimed at providing a potent therapeutic alternative to conventional drugs in the management of liver and kidney diseases.MethodologyCarbon tetrachloride (3 ml/kg bw) and rifampicn (250 mg/kg bw) were administered to induce liver and kidney damage in selected groups of albino rats. Graded doses of Sida acuta leaves extract as well as silymarin (200 mg/kg bw) were then post-administered to experimental animals placed into eight groups of five animals each. Biomarkers of oxidative stress such as lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (ALT), alkaline phosphatase (ALP), superoxide dismutase (SOD), catalase (CAT), urea, uric acid, bilirubin and malonidialdehyde (MDA) were determined. Histopathological observations of both renal and hepatic tissues of experimental animals were also performed.ResultsAnimals exposed to CCl4 and rifampicin without treatment exhibited significant derangement in lipid profile, elevated levels of ALT, ALT, ALP, urea, uric acid, bilirubin and MDA in the serum and tissues homogenates. Superoxide dismutase and catalase activities were significantly inhibited while level of GSH was depleted. Following treatment with S. acuta extract, all deranged parameters including histological alterations were restored in a dose-dependent manner comparable to animals treated with silymarin.ConclusionBiochemical and histopathological data obtained from the present study confirmed that Sida acuta is a potential antioxidant plant that can be exploited in the management of liver and kidney dysfunctions.

Ficus Carica Reduces Serum Uric Acid Level in Hyperuricemic Rats

Background: Ficus carica has been broadly used as traditional medicine around the world. Less toxicity of this plant represent its possible uses as therapeutic remedy for several disorders. In folk medicine, Ficus carica fruit has been used to treat hyperuricemia and associated conditions like gout and renal stones. However, no scientific work has been done so far to observe these effects. Aim and Objective: To assess that Ficus carica (Fig fruit) extract can lessen the elevated blood levels of uric acid in hyperuricemia induced by potassium oxonate in rats. Place and Duration of Study: The study was carried out at the Pharmacology Department of Post Graduate Medical Institute, Lahore and completed in six months. Methods: Thirty-six rats were divided randomly into six groups. Group A was the negative control. Group B was the positive control and rats in this group were given potassium oxonate intraperitoneally (250 mg/kg) to induce hyperuricemia. Group C received potassium oxonate and allopurinol (5mg/kg) also. Group D, E, & F received potassium oxonate and Ficus carica in three different doses low (250mg/kg), medium (500 mg/kg), and high (750 mg/kg) respectively. In all groups, potassium oxonate was administered on days one, three and seven while test agents were administered for seven consecutive days. Sampling was done on day zero, one, three and seven. Results: In experimental animals, Ficus carica fruit extract decreased serum levels of uric acid in dose dependent manner. It reduced uric acid levels significantly (p value < 0.001) in medium and high dose extract groups as compared to hyperuricemic control group. Serum uric acid levels in medium dose group E (2.8 + 0.54) and low dose group F (2.5 + 0.31) were comparable to that of allopurinol group C (2.2 + 0.27) though this effect was observed earlier in allopurinol group C indicating quicker onset of allopurinol action. Conclusion: Fiscus carica features antihyperuricemic effects. It resulted in significant decrease in levels of uric acid in serum of the extract treated animals in doses of 500mg/kg and 750mg/kg. Keywords: Ficus carica, Hyperuricemia, Potassium oxonate, Serum uric acid (SUA), Xanthine Oxidase.

Variation of Serum Uric Acid Is Associated With Gut Microbiota in Patients With Diabetes Mellitus.

Diabetes mellitus is a metabolic disease closely related to a disordered gut microbiome. Diabetic patients usually suffer from various metabolic disorders, such as increased serum uric acid levels. Although serum uric acid levels depend partially on intestine excretion, the relationship between uric acid and gut microbiome in diabetic patients remains unknown. We collected a total of 126 fecal samples from diabetic patients for 16S ribosomal RNA gene amplicon sequencing and recorded clinical data. We analyzed the correlation between clinical indicators and gut microbiota of diabetic patients using Spearman analysis. Since uric acid was the most prominent one, we classified diabetic patients based on their uric acid levels to find the microbiome associated with uric acid disturbance. We constructed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway profiles using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to identify variations between the different groups. Among all the clinical indicators, uric acid had the strongest correlation with gut microbiota. First, we divided the patients into three groups according to their uric acid levels. The two low uric acid groups were similar, while the elevated uric acid group had significant differences in gut microbiota and metabolic pathways. The elevated uric acid group had a significantly lower gut microbiota diversity. At the genus level, this group had remarkably higher Escherichia–Shigella amounts and notably lower Faecalibacterium, Oscillospiraceae_UCG−002, and Oscillospiraceae_UCG−005 amounts. The gut microbiota of the high uric acid group was predicted to be enriched in metabolism, human diseases, and lipopolysaccharide biosynthesis. Since the two low uric acid groups were similar, we regrouped and matched the abnormal uric acid patients with normal uric acid patients. The differences in gut microbiota and metabolic pathways related to nucleotide metabolism became more significant. The serum uric acid levels were associated with gut microbiome changes. This might be related to uric acid metabolism by gut microbes. Our study indicates that targeting the gut microbiome could help manage elevated uric acid levels.

Serum Uric Acid Might Be Positively Associated With Hypertension in Chinese Adults: An Analysis of the China Health and Nutrition Survey.

Background: Previous studies have clarified the relationship between serum uric acid (SUA) and hypertension; most of previous studies suggest that elevated uric acid levels are associated with an increased risk of hypertension, while in China, there are relatively few studies to explore above association. The objective of this longitudinal study is to investigate the correlation of SUA and hypertension in Chinese adults with a nationwide large-scale sample.Methods: Data from the China Health and Nutrition Survey 2009, 2011, and 2016 were used; a total of 8,469 participants (3,973 men and 4,496 women) were involved. This study was conducted separately by gender. Clinical characteristics of the participants among different uric acid groups are compared. The binary logistic regression analysis was conducted to examine the association between SUA and hypertension. Restricted cubic spline analysis with three knots of the SUA concentration were used to characterize the dose-response relationship. Additionally, we compared the incidence of hypertension in the different baseline uric acid groups during follow-up in 2011 and 2015.Results: After the covariates were fully adjusted, we found that elevated uric acid levels were correlated with increased risk of hypertension in both males (p < 0.01) and females (p < 0.01). With 2-year or 6-year of follow-up, we found participants with higher baseline uric acid levels had a higher incidence of hypertension (p < 0.01). In stratified analysis by obesity, above relationship remained significant in nonobesity population (males: p < 0.05, females: p < 0.01) and became nonsignificant in obesity people. In stratified analysis by age, above positively correlation remained significant in middle-aged men (p < 0.05) and elderly women (p < 0.01). Restricted cubic spline revealed the dose-response relationship between SUA and hypertension; we also found that above relationship was much stronger in females.Conclusion: This study suggests that elevated SUA levels might be positively associated with an increased risk of hypertension in general Chinese adults.

Changes of serum uric acid and its clinical correlation in children with dilated cardiomyopathy.

BackgroundDilated cardiomyopathy (DCM) is the most common type of childhood cardiomyopathy and uric acid (UA) is considered closely associated with cardiovascular disease. There are few reports about the relationship between serum UA level and DCM in children, and the present study aimed to analyze the changes and clinical correlation of the two.MethodsThe clinical data of 49 children under 16 years old and who were hospitalized with DCM, and 44 healthy children who underwent physical examination in the same period at Tianjin Children’s Hospital from June 2015 to November 2019 were analyzed retrospectively.ResultsThe 49 children in the case group included 17 males and 32 females, aged from 2 to 172 months. The case group were divided into New York Heart Association (NYHA) functional class I (n=2), class II (n=17), class III (n=11), and class IV (n=19). The 44 healthy children selected as the control group included 20 males and 24 females aged from 2 to 161 months. The serum UA level was detected, and an ultrasonic cardiogram was conducted in each child. The serum UA level, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left atrial diameter (LAD) of the case group were higher than that of the control group, while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower than that of the control group, and significant statistical differences were seen between the two groups (P<0.01). The serum UA level, LVEDD, LVESD, and LAD of NYHAIII–IV class patients were higher than that of the NYHAI–II class, but LVEF and LVFS were lower than that of the NYHA I–II class, and there were significant statistical differences between the two groups (P<0.01). Statistical correlations were seen between the serum UA level and NYHA functional class, LVEDD, LVESD, LAD, LVEF, and LVFS (rs=0.599, 0.567, 0.579, 0.475, −0.333, −0.341, respectively, P<0.05).ConclusionsElevated serum UA levels exist in children with DCM and correlate with NYHA functional class and ultrasonic values. Change in serum UA levels may be used as a biomarker reflecting the severity of DCM in children.

Experimental safety testing shows that the NSAID tolfenamic acid is not toxic to Gyps vultures in India at concentrations likely to be encountered in cattle carcasses

Population declines of Gyps vultures across the Indian subcontinent were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Subsequently, a number of other NSAIDs have been identified as toxic to vultures, while one, meloxicam, is safe at concentrations likely to be encountered by vultures in the wild. Other vulture-safe drugs need to be identified to reduce the use of those toxic to vultures. We report on safety-testing experiments on the NSAID tolfenamic acid on captive vultures of three Gyps species, all of which are susceptible to diclofenac poisoning. Firstly, we estimated the maximum level of exposure (MLE) of wild vultures and gave this dose to 40 Near Threatened Himalayan Griffons G. himalayensis by oral gavage, with 15 control birds dosed with benzyl alcohol (the carrier solution for tolfenamic acid). Two birds given tolfenamic acid died with elevated uric acid levels and severe visceral gout, while the remainder showed no adverse clinical or biochemical signs. Secondly, four G. himalayensis were fed tissues from water buffaloes which had been treated with double the recommended veterinary dose of tolfenamic acid prior to death and compared to two birds fed uncontaminated tissue; none suffered any clinical effects. Finally, two captive Critically Endangered vultures, one G. bengalensis and one G. indicus, were given the MLE dose by gavage and compared to two control birds; again, none suffered any clinical effects. The death of two G. himalayensis may have been an anomaly due to i) the high dose level used and ii) the high ambient temperatures at the time of the experiment. Tolfenamic acid is likely to be safe to Gyps vultures at concentrations encountered by wild birds and could therefore be promoted as a safe alternative to toxic NSAIDs. It is manufactured in the region, and is increasingly being used to treat livestock.

Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis.

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

C-reactive Protein, Free Fatty Acid, and Uric Acid as Predictors of Adverse Events after Endovascular Revascularization of Arterial Femoropopliteal Occlusion Lesions

This study aimed to investigate the relationship between pre-procedure high-sensitivity C-reactive protein (hsCRP), free fatty acid (FFA), and uric acid (UA) levels and post-procedure mortality and morbidity of endovascular revascularization of arterial femoropopliteal occlusion lesions. This was a retrospective review of clinical data retrieved from a prospectively held database in Peking Union Medical College Hospital. A total of 71 Patients who underwent endovascular treatment (EVT) for femoropopliteal occlusive disease between January 1, 2014 and November 1, 2017, were included in this study. Endpoints were defined as major adverse limb events (MALE; target vessel revascularization, amputation, or disease progression) and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or all-cause death) during the entire follow-up period. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the relationship of elevated biomarker levels (hsCRP, FFA and UA, measured by immunoturbidimetry assay, enzymatic assay and enzymatic assay, respectively) to MALE and MACE outcomes. Seventy-one patients (72 limbs) with sufficient follow-up information were included in the analysis. The mean age was 69.7 ± 8.6 years; 21.1% were female. The Rutherford class of target limbs were ≥ 3. The median follow-up was 36 (range 18-59 months). Univariate analyses revealed that patients with elevated hsCRP levels had an increased risk of MALE (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.281-5.617, P=0.009). High FFA levels were associated with an increased risk of MALE (HR, 2.658; 95% CI, 1.075-6.573; P=0.034). Multivariate analyses demonstrated that elevated hsCRP values (HR, 4.015; 95% CI, 1.628-10.551; P=0.003) and FFA value (HR, 3.034; 95% CI, 1.102-8.354; P=0.032) were both significantly associated with increased MALE. Elevated UA levels predicted MACE in the presence of confounders (HR, 11.446; 95% CI, 1.367-95.801 P=0.023). Pre-procedure hsCRP and FFA levels could serve as predictors of adverse events after EVT in patients with arterial femoropopliteal occlusive disease. The role of UA in MACE may warrant further investigation, because the correlation is not as powerful as the other two in the study.

Eurycomanol alleviates hyperuricemia by promoting uric acid excretion and reducing purine synthesis

BackgroundAn elevated level of blood uric acid (UA) leads to serious damages to human health. In clinic, xanthine oxidase inhibitor is commonly used to reduce uric acid production. However, UA excretion promotion drug is rare. Our previous study demonstrated that the 70% ethanolic extract of stem of Eurycoma longifolia could effectively increase UA excretion and decrease blood level of UA in hyperuricemia animal model. In this paper, we tried to find active substance on UA regulation from E. longifolia. MethodsThe constituents of stem from E. longifolia were isolated and analyzed by chemical and spectral methods. Ultra Performance Liquid Chromatography was applied to measure the concentrations of UA in serum and urine. H&E staining was used to characterize renal histopathological changes. The protein and mRNA expressions of UA transporters were measured by western blot and quantitative real-time PCR analysis. ResultsTen kinds of quassinoids were isolated from stem of E. longifolia, and the structures were identified. Pharmacological research revealed the major component, eurycomanol (5–20 mg/kg, p.o.) significantly decreased serum UA level and increased 24 h clearance of uric acid in potassium oxonate and adenine induced hyperuricemic mice. Eurycomanol ameliorated UA induced kidney histological injury, inhibited hepatic purine synthesis through decreasing phosphoribosyl pyrophosphate synthetase, promoted UA excretion by modulation of renal and intestinal urate transporters, such as GLUT9, ABCG2, OAT1, and NPT1. ConclusionThe results showed eurycomanol from E. longifolia can promote UA excretion through kidney and intestine, decrease hepatic purine synthesis and further keep UA homeostasis, suggesting that eurycomanol has the potential to be developed into a novel drug for the treatment of under-excretion type hyperuricemia.

Ameliorative Effects of Gallic Acid on Cisplatin-Induced Nephrotoxicity in Rat Variations of Biochemistry, Histopathology, and Gene Expression

Background Cisplatin is a powerful chemotherapeutic drug mainly used in the treatment of solid tumors. Aggregation of the drug in renal proximal tubule cells causes nephrotoxicity and renal failure. Investigations showed nephrotoxicity as Cisplatin's dose-limiting side effect. One of the Cisplatin toxicity mechanisms is generation of reactive oxygen species, which leads to oxidative stress and renal damage. The purpose of this study was evaluation of the modulating effects of Gallic acid on Cisplatin-induced variations including Caspase-3 and Clusterin expression and histopathological and biochemical parameters in adult male Wistar rats. Method Rats were kept under standard condition of temperature, light, and humidity. The animals were divided into 4 groups: GpI: control group (received distilled water for 10 days); GpII: Gallic acid (alone) (50 mg/kg bw, once a day for 10 days); GpIII: Cisplatin (alone), single dose (6 mg/kg bw, I.P. on 5th day of study); GpIV: Gallic acid (50 mg/kg bw, once a day for 10 days) and also injected with single dose of Cisplatin (6 mg/kg bw, I.P., on 5th day of study). After 10 days, all rats were anaesthetized and plasma collected to estimate urea, creatinine, and uric acid. The right kidneys were removed for the study of gene expression and biochemical parameters. The left kidneys were used for histopathological studies. Results The Cisplatin-induced nephrotoxicity was evident from the elevated levels of creatinine, urea, uric acid, and renal tissue MDA and also decreased levels of SOD, CAT, GPX, and GSH in renal tissue. Administration of Gallic acid significantly modulated nephrotoxicity markers, gene expression variations, and histopathological damage. Conclusion Outcomes of the present investigation suggest that Gallic acid provides protection against CP-induced nephrotoxicity, but for application in people, further studies are needed.

Elevated blood favipiravir levels are inversely associated with ferritin levels and induce the elevation of uric acid levels in COVID-19 treatment: A retrospective single-center study

IntroductionMeasurement of blood Favipiravir (FPV) levels and accumulation of data in COVID-19 patients are critical for assessing FPV efficacy and safety. We performed a retrospective study based on measurements of blood levels of FPV and related factors in COVID-19 patients admitted to our hospital. Furthermore, we also investigated the association between blood FPV levels and uric acid level alterations before and after FPV administration. MethodsWe enrolled 27 COVID-19 patients who had received FPV treatment at Hokushin General Hospital from April 1 to December 31, 2020. Age, gender, COVID-19 severity, presence of comorbidities, and laboratory data for each subject were investigated to identify factors that correlate with blood FPV levels. Uric acid levels were measured before and after FPV administration and a difference between the levels (i.e., a change of uric acid level) was evaluated. ResultsWhen a significant univariate variable was input by the stepwise method and a combination of variables that maintained statistical superiority was searched, serum ferritin was the only factor that independently affected blood FPV level. Furthermore, in the high-FPV group (20 μg/mL or more), a significant increase in uric acid levels was observed after FPV administration. The increment value was significantly larger than that in the low-FPV group (less than 20 μg/mL). ConclusionsFerritin level was an important independent factor inversely affecting blood FPV level. Furthermore, a high blood FPV level induced the elevation of uric acid levels in COVID-19 treatment.

Serum uric acid in early pregnancy and risk of gestational diabetes mellitus: A cohort study of 85,609 pregnant women

AimsHigher serum uric acid (UA) has been associated with increased risk of Type 2 diabetes mellitus. This cohort study examined whether there are any associations between serum UA in early pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). MethodsThis cohort study was conducted in Shanghai, China, and included 85,609 pregnant women. Generalised additive models were used to estimate the associations of serum UA with risk of GDM. ResultsThe prevalence of GDM was 14.0% (11,960/85,609). Non-linear associations between serum UA and GDM risk were observed and these associations varied by gestational ages. Only elevated serum UA levels at 13–18 weeks gestation was associated with substantially increased risk of GDM. Analysis by UA quintiles at 13–18 weeks gestation showed the odds ratios for GDM were 1.11 (95%CI, 1.03–1.20) for the second, 1.27 (95%CI, 1.17–1.37) for the third, 1.37 (95%CI, 1.27–1.48) for the fourth and 1.70 (95%CI, 1.58–1.84) for the fifth quintile of serum UA in comparison with the first quintile. Stratified analysis showed the associations of serum UA with GDM were stronger among pregnant women aged 35 years or older. ConclusionWe found higher serum UA at 13–18 gestational weeks was a risk factor for GDM. Our findings provide new evidence for the role of serum UA in the prevention and early intervention of GDM, and highlighted the need for monitoring serum UA at 13–18 gestational weeks.

Altered structural changes of podocytes, glomerular basement membrane in patients with type 2 diabetes mellitus

Diabetic nephropathy is a one of the microvascular complication in patients with type 2 diabetes mellitus due to increased production of free radicals and decreased levels of anti oxidants. The seviority of the disease totally depends on due to damage of foot process of podocytes. Hence, we need to evaluate the altered structural changes of podocytes, glomerular basement membrane in patients with type 2 diabetes mellitus. A total 60 type 2 diabetes mellitus patients were included in the present study and again sub classified into 2 types (Normoalbuminuria 30, Microalbuminuria 30) based on their urinary ACR. Basic laboratory investigations and radio graphical data were collected from the all subjects. A statistical was performed by using SPSS Version 21.0 and P value considers &amp;#60; 0.05 is statistically significant. The significantly elevated levels of plasma FBS, PPBS, Serum Urea, Creatinine, Uric Acid and HbA1c, Urinary albuminuria observed in type 2 diabetes mellitus with microalbuminuria when compared to normoalbuminuria. The radiographical data showed a significantly damaged foot process of podocytes and glomerular basement membrane are observed in patients with microalbuminuria when compared to normoalbuminuria. The increased levels blood sugar and HbA1c, Urinary Albuminuria directly indicates the damage of podocytes and glomerular basement membrane in the kidney. This study suggest continuous monitoring of these parameters may helpful for progression of type 2 diabetes mellitus complications.

Dietary Acid Load Is Positively Associated with the Incidence of Hyperuricemia in Middle-Aged and Older Korean Adults: Findings from the Korean Genome and Epidemiology Study.

Hyperuricemia has been associated with a number of chronic diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Dietary acid load plays a key role in regulating uric acid levels. We hypothesized that potential renal acid load (PRAL) and net endogenous acid production (NEAP) score would be positively associated with the incidence of hyperuricemia. Data from the Health Examinees study, a part of the Korean Genome and Epidemiology Study were used. The PRAL and NEAP scores were calculated to evaluate the dietary acid load. Hyperuricemia was defined as follows: >7.0 mg/dL and >6.0 mg/dL of serum uric acid levels in men and women, respectively. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of hyperuricemia. We identified 2500 new cases of hyperuricemia during a mean follow-up of 5.0 years (223,552 person years). The participants in the highest quartiles of the PRAL and NEAP score had 21% (HR: 1.21, 95% CI: 1.07–1.35, p for trend <0.0001) and 17% (HR: 1.17, 95% CI: 1.04–1.31, p for trend <0.0001) higher risks for hyperuricemia, respectively, than those in the lowest quartiles, after adjusting for covariates. In this prospective cohort study, a higher dietary acid load was positively associated with a higher incidence of hyperuricemia in Korean adults. This suggests that an alkaline diet may be an effective strategy to reduce the future risk of elevated uric acid levels.