Plasma Uric Acid Levels Research Articles

Correlative Study of Bone-related Biochemicals and Endocrine Changes in Perimenopausal Women in Enugu, Nigeria.

Perimenopause is a physiological occurrence in women, and is characterized by endocrine and biochemical changes. During perimenopause phase, many derangements or abnormal health conditions start developing as a result of hormonal changes. These derangements in health conditions and biochemical changes lead to higher incidence of metabolic syndrome (MetS) occurrence with or without bone involvement. There is a scarcity of information on MetS in Enugu, Southern Nigeria and there is no available data on the correlation of selected bone-related biochemicals with endocrine parameters and MetS in perimenopausal women from the region. We consecutively sampled 200 apparently healthy women, and categorized them into 120 perimenopausal women (age (!) = 50years) and a second group of 80 women in premenopause (age (!) = 35years). Measurement of anthropometric indices like blood pressure, height, weight and waist circumference were taken. Fasting blood samples were collected for the estimation of endocrine parameters (estradiol (E₂), follicle stimulating hormone (FSH), and luteinizing hormone (LH)) using enzyme linked immunosorbent assay (ELISA) technique. The lipid profile, fasting plasma glucose (FPG), uric acid, inorganic phosphate, calcium and alkaline phosphatase levels were determined using standard biochemical methods. The evaluation of MetS was carried out in the women using the three different criteria: World Health Organization (WHO), National Cholesterol Education Program- Adult Treatment Panel 111 (NCEP-ATP 111) and International Diabetes Federation (IDF). For statistical analysis, Student's t-test, Pearson correlation and Chi-square were used to compare categorical and continuous variables. Calcium was predominantly high in the three criteria (p<0.05). LH and FSH showed a positive correlation with FPG while E₂ was negatively associated with FPG. Similarly, LH showed a positive association with inorganic phosphate while E₂ was negatively associated with alkaline phosphatase (p<0.05). Perimenopausal women are at higher risk of developing osteoporosis than premenopausal women. This emphasizes the need for timely diagnosis of osteoporosis in perimenopausal women.

Sodium-glucose cotransporter2 inhibitors: A drug with antidiabetic and cardioprotective properties.

Recently, two large double-blind randomized controlled trials testing the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure with and without diabetes have led to a paradigm shift for the indication of this class of drugs. Key clinical features and main results in these two studies are summarized in Table 1 and 2. The dapagliflozin and prevention of adverse outcomes in heart failure (DAPA-HF) trial included 4744 patients with heart failure and a reduced ejection fraction (HFrEF).

Metabolic cardio- and reno-protective effects of empagliflozin in a prediabetic rat model.

The mechanisms behind the cardiovascular and renal benefits of empagliflozin is not fully understood. The positive impact of the medication on cardiovascular mortality can not be solely attributed to its antidiabetic effect, with a metabolic mechanism possibly involved. To investigate the metabolic effects of empagliflozin treatment (10 mg/kg/day for 6 weeks), we used an adult male rat model with serious vascular complications associated with metabolic syndrome and prediabetes. Impaired glucose tolerance, severe albuminuria and impaired insulin sensitivity were induced by intragastric administration of methylglyoxal and high sucrose diet feeding for four months. Although empagliflozin decreased body weight, non-fasting glucose and insulin, glucagon levels remained unchanged. In addition, empagliflozin increased adiponectin levels (+40%; p < 0.01) and improved skeletal muscle insulin sensitivity. Increased non-esterified fatty acids (NEFA) in empagliflozin-treated rats is understood to generate ketone bodies. Empagliflozin increased β-hydroxybutyrate levels in serum (+66%; p < 0.05) and the myocardium (30%; p < 0.01), suggesting its possible involvement as an alternative substrate for metabolism. Empagliflozin switched substrate utilisation in the myocardium, diverting glucose oxidation to fatty acid oxidation. Representing another favorable effect, empagliflozin also contributed to decreased uric acid plasma levels (-19%; p < 0.05). In the kidney cortex, empagliflozin improved oxidative and dicarbonyl stress parameters and increased gene expression of β-hydroxybutyrate dehydrogenase, an enzyme involved in ketone body utilisation. In addition, empagliflozin decreased microalbuminuria (-27%; p < 0.01) and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion (-29%; p < 0.01). Our results reveal the important systemic metabolic effect of empagliflozin on alterations in substrate utilisation and on increased ketone body use in prediabetic rats. Improved oxidative and dicarbonyl stress and decreased uric acid are also possibly involved in the cardio- and reno-protective effects of empagliflozin.

The Time-Feature of Uric Acid Excretion in Hyperuricemia Mice Induced by Potassium Oxonate and Adenine.

Hyperuricemia is an important risk factor of chronic kidney disease, metabolic syndrome and cardiovascular disease. We aimed to assess the time-feature relationship of hyperuricemia mouse model on uric acid excretion and renal function. A hyperuricemia mouse model was established by potassium oxonate (PO) and adenine for 21 days. Ultra Performance Liquid Chromatography was used to determine plasma uric acid level. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and Western blot was used to detect renal urate transporters’ expression. In hyperuricemia mice, plasma uric acid level increased significantly from the 3rd day, and tended to be stable from the 7th day, and the clearance rate of uric acid decreased greatly from the 3rd day. Further study found that the renal organ of hyperuricemia mice showed slight damage from the 3rd day, and significantly deteriorated renal function from the 10th day. In addition, the expression levels of GLUT9 and URAT1 were upregulated from the 3rd day, while ABCG2 and OAT1 were downregulated from the 3rd day, and NPT1 were downregulated from the 7th day in hyperuricemia mice kidney. This paper presents a method suitable for experimental hyperuricemia mouse model, and shows the time-feature of each index in a hyperuricemia mice model.

The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome

BackgroundWomen with polycystic ovary syndrome (PCOS) are characterized by increased cardiometabolic risk. The aim of the current study was to compare the impact of atorvastatin on plasma levels of cardiometabolic risk factors between men whose sisters had either PCOS or were unaffected.MethodsThe study population consisted of two age-, fat-free mass index-, blood pressure- and plasma lipid-matched groups of men with elevated total and LDL cholesterol levels: 20 brothers of PCOS probands (group 1) and 20 brothers of healthy women (group 2). Both groups were then treated with atorvastatin (40 mg daily) for the following 6 months. At the beginning and at the end of the study, we assessed plasma lipid levels, glucose homeostasis markers and levels of dehydroepiandrosterone sulfate, testosterone, bioavailable testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and 25-hydroxyvitamin D.ResultsAt the beginning of the study, both treatment arms differed in the degree of insulin resistance, calculated bioavailable testosterone, as well as in plasma levels of dehydroepiandrosterone sulfate, uric acid, hsCRP and 25-hydroxyvitamin D. Although atorvastatin reduced total and LDL cholesterol levels, this effect was stronger in group 2 than group 1. In group 2, atorvastatin exerted also a more potent impact on hsCRP, fibrinogen and homocysteine. An unfavorable impact on insulin sensitivity was observed only in group 1; while, statistically significant changes in uric acid and 25-hydroxyvitamin D levels were found only in group 2.ConclusionThe obtained results suggest that cardiometabolic effects of atorvastatin are less pronounced in male siblings of PCOS probands than in brothers of unaffected women.

Uric acid levels in subjects with schizophrenia: A systematic review and meta-analysis

The association between schizophrenia (SZ) and uric acid (UA) levels has been suggested for many years, but without solid evidence. Therefore, we conducted a systematic review and meta-analysis of all case-control studies examining the serum and plasma UA levels in SZ subjects in comparison to those in healthy controls. Relevant studies published before October 29, 2018, were searched in the main electronic databases, and 17 studies were finally included into the meta-analysis after screening with the criteria. Our results revealed that there were no statistically significant differences of the UA levels between SZ subjects and healthy controls. Further subgroup analyses of the antipsychotic status reported the same finding. Subgroup analyses of clinical status showed that UA levels were decreased in subjects with first episode psychosis (FEP). The subgroup analyses of gender and ethnicity demonstrated that UA levels were decreased in male subjects and in Americans with SZ. Overall, these findings strengthen the clinical evidence that FEP is accompanied by increased oxidative stress response. Reduced UA levels may be a potential risk factor for SZ in male and in the Americans. However, whether there is a causal relationship between the reduced UA levels and the development of SZ deserves further investigation.

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.

Effects of low-dose milk protein supplementation following low-to-moderate intensity exercise training on muscle mass in healthy older adults: a randomized placebo-controlled trial

PurposeThe purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate.MethodsIn a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60–84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry.ResultsLean body mass significantly increased in the MILK group (+ 0.54 kg, p < 0.001), but did not change in the PLA group (− 0.10 kg, p = 0.534). The increases in the MILK group were significantly greater than in the PLA group (p = 0.004). Fat mass (− 0.77 kg) and plasma uric acid levels (− 0.3 mg/dL) significantly decreased only in the MILK group (p < 0.001), with a significant group difference (p = 0.002 and p < 0.001, respectively). Most of the physical performance tests significantly improved in both groups, but no group differences were found.ConclusionWe conclude that low-dose milk protein supplementation (10 g of protein/day) combined with low-to-moderate intensity exercise training is associated with increased muscle mass, but not improved physical performance compared to carbohydrate combined with exercise in healthy older adults. This study was registered in the UMIN Clinical Trials Registry (UMIN000032189).

The high-fructose intake of dams during pregnancy and lactation exerts sex-specific effects on adult rat offspring metabolism.

Experimental studies have demonstrated the effects of maternal fructose consumption during pregnancy and lactation on metabolic alterations in their offspring, especially male offspring. However, few studies have focused on female offspring after providing fructose in food to dam rats. Here, we studied whether offspring of both sexes were differentially affected by a maternal high-fructose diet (HFD). For this purpose, Sprague-Dawley rats were fed during pregnancy and lactation with a standard diet (SD) or a HFD (50% w/w). After weaning, offspring were fed an SD; 3 days later, dams were sacrificed, and their offspring were sacrificed on postnatal day 90. Body weight (BW), food and water intake (only for dams), and various biomarkers of metabolic syndrome were measured. When compared to the SD-fed dams, HFD-fed dams had a reduction in BW and food and water intake. Conversely, adiposity, liver weight, liver lipids, and plasma levels of glucose, insulin, cholesterol, triglycerides, and uric acid were increased in HFD-fed dams. Moreover, the BW, food consumption, weight of retroperitoneal fat pads, and liver lipids increased in female and male offspring of HFD-fed dams. Interestingly, the pups of HFD-fed mothers showed increased levels of leptin and insulin resistance and decreased levels of adiponectin which were more pronounced in male offspring than in female offspring. In contrast, a higher increase in BW was shown earlier in female offspring. Thus, high-fructose consumption by dams during pregnancy and lactation led to sex-specific developmental programming of the metabolic syndrome phenotype in adult offspring.

SAT-651 Ethnic Differences in the Relationship Between Uric Acid Clearance and Insulin Sensitivity

Background: Hyperuricemia is associated with gout, type-2 diabetes, hypertriglyceridemia, and other insulin resistant (IR) states. Impaired clearance of uric acid (UA) has been proposed to play a role in hyperuricemia in IR. In a small study, urinary UA clearance was negatively associated with IR. African-Americans (AA) are more insulin resistant than Caucasians (CA). However, plasma UA levels are lower in AA. Ethnic differences underlying the relationship between UA clearance and insulin sensitivity (Si) remain unknown. Objective: To compare the relationships between UA production, clearance, and Si in AA and CA. Design: In a cross-sectional study, AA (n = 40; age 43 ± 10 years; BMI 41.3 ± 9.7 kg/m2) and CA (n = 88; age 44 ± 13 years; BMI 32.9 ± 8.2 kg/m2) subjects underwent an intravenous glucose tolerance test (IVGTT) to derive Si using the Minimal Model. Plasma UA and creatinine (Cr), were measured in the NIH Department of Laboratory Medicine. Urinary UA and Cr levels in spot urine samples were measured using a colorimetric assay. Fractional Excretion (FE) of UA and urine urate-to-creatinine ratio (UUCR), a measure of uric acid production, were calculated. Results: AA had a significantly higher BMI (p < 0.0001), percent body fat (45.8 ± 8.9 vs. 39.7 ± 11.5 %, p = 0.0007), A1C (5.8 ± 0.4 vs. 5.5 ± 0.3 %, p = 0.0006), diastolic BP (74 ± 9 vs. 71 ± 8 mm of Hg, p = 0.02), and lower Si (2.36 ± 2.7 vs. 4.43 ± 3.4 min−1·μU·ml−1, p = 0.0004) compared to CA. Stepwise multiple regression analysis was performed with independent variables A1c, fasting glucose, fasting insulin, triglycerides, and Si. Among these, Si was a significant predictor of FE of UA in CA (r = 0.33, p=0.001), but not AA (r = - 0.02, p=0.92).There was also a negative association between Si and plasma UA in CA (r = 0.48, p < 0.0001), but not in AA (r = 0.06, p = 0.70). There was no association between Si and UA production in both groups (AA: p = 0.33, CA: p = 0.69). Conclusion: These findings suggest that reduced insulin sensitivity may not play a major role in the pathogenesis of hyperuricemia in AA in insulin-resistant states.

Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function.

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females.

Abstract #842660: Effect of Protein-Sparing Modified Fast Diet on Plasma Levels of Lipids, Uric Acid, and Liver Enzymes

Abstract #842660: Effect of Protein-Sparing Modified Fast Diet on Plasma Levels of Lipids, Uric Acid, and Liver Enzymes

Antioxidant Activities of Green Synthesized Zinc Oxide Nanoparticles and its Curative Influence in Carbon tetrachloride‐Induced Hepatorenal Damage in Adult Rats

The objective of this study was to synthesize Zinc Oxide nanoparticles coated with Pterocarpus mildbraedii leaf extracts (PmZnONPs) by an eco‐friendly method, and investigate its antioxidant activity and curative potential against carbon tetrachloride (CCl4) ‐ induced hepatorenal toxicity in rats. PmZnONPs was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), fourier transform infra‐red spectroscopy (FTIR), alongside zeta potential measurement. In vitro, free radical activities using 1, 1‐diphenyl‐2‐ picrylhydrazyl (DPPH) and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) showed strong antioxidant activity compared to ascorbic acid. In rats, PmZnONPs (1 and 3 mg/kg p.o.) significantly prevented CCl4‐induced elevations of alkaline phosphatase, gamma‐glutamyl transferase, creatinine, urea, aspartate aminotransferase, alanine aminotransferase, and total bilirubin. Moreover, PmZnONPs restored the decreased levels of plasma uric acid, hepatorenal antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione transferase, and glutathione, that were significantly induced by CCl4 treatment. Histological studies indicated that CCl4‐induced lesions in the liver and kidney were alleviated by the treatment of PmZnONPs. Immunohistochemical studies showed that PmZnONPs significantly suppressed the high immunoreactivity of cyclooxygenase‐2, interleukin‐6 and NF‐κB arising from CCl4 intoxication. These results indicated that PmZnONPs protected the rats from CCl4‐induced hepatorenal damage via its antioxidant properties as well as its inhibition of pro‐inflammatory proteins.Support or Funding InformationThis research did not receive any support from any funding organization.

Modulatory Effects of Acute Aerobic Moderate Exercise on Purinergic Enzymes in Sedentary and Physically Active Males

Exercise promotes biochemistry and physiological adaptations, leading to health benefits. Purinergic signaling is a well‐known system of cellular communication, based in extracellular nucleotides and nucleosides that modulate inflammatory, coagulatory and vascular activities. However, data about the effects of exercise in purinergic signaling remain limited. Thus, the main goal of present work was to evaluate the influence of acute aerobic moderate exercise on blood plasma nucleotidases in eutrophic sedentary (EUSED), overweight sedentary (OWSED) and physically active (ACT) male individuals. This study was approved by local Ethics Committee under protocol 2.452.427, being in agreement with the declaration of Helsinki. Twenty‐four healthy male individuals were divided into 3 groups: EUSED (N=8, BMI=23.51±2.01 Kg/m2, 26.38±2.97 years), OWSED (N=8, BMI=27±76 Kg/m2, 25.75±2.92 years) and ACT (N=8, BMI=23.96±1.35 Kg/m2, 23.13±3.18 years). Subjects were evaluated to collect clinical data and performed a cardiopulmonary exercise test to maximal oxygen uptake (VO2MAX) determination. Seven days after evaluation, subjects realized 30 minutes of exercise on treadmill with 70% VO2MAX. Blood samples were taken pre‐, post‐exercise and post‐1h of exercise. NTPDases and 5′‐nucleotidase activities were quantified by release of inorganic phosphate from ATP, ADP and AMP hydrolysis. NPP activity was assessed using p‐Nph‐5′‐TMP as substrate. Adenine nucleotides and nucleosides were quantified by HPLC. Data were analyzed using two‐way ANOVA repeated measures. ATP (EUSED: p=0.001; OWSED: p=0.015; ACT: p=0.002), ADP (EUSED: p=0.001; OWSED: p=0.009; ACT: p=0.001), AMP (EUSED: p=0.001; OWSED: p=0.001; ACT: p=0.001) and p‐Nph‐5′‐TMP (EUSED: p=0.001; OWSED: p=0.001; ACT: p=0.001) hydrolysis increased from pre‐ to post‐exercise among the groups. Post‐1h after exercise, ATP hydrolysis remained increased in ACT group (p=0.019), ADP in OWSED (p=0.03) and AMP in OWSED (p=0.001) and ACT (p=0.03). ATP (EUSED: p&lt;0.001; OWSED: p&lt;0.001; ACT: p&lt;0.001) and ADP (EUSED: p&lt;0.001; OWSED: p&lt;0.001; ACT: p&lt;0.001) plasma levels decreased from pre‐ to post‐exercise and remained decreased post‐1h after exercise among the groups. Adenosine (EUSED: p&lt;0.001; OWSED: p=0.011; ACT: p=0.01), inosine (EUSED: p&lt;0.001; OWSED: p&lt;0.001; ACT: p&lt;0.001) and uric acid (EUSED: p&lt;0.001; OWSED: p=0.001; ACT: p=0.021) plasma levels increased from pre‐ to post‐exercise. Adenosine levels remained increased post‐1h exercise in all groups. There was no significant differences among the groups. Our results indicate that acute aerobic moderate exercise transiently increases NTPDases, 5′‐nucleotidase and NPP activities in plasma, decreasing levels of pro‐inflammatory and pro‐thrombotic molecules as ATP and ADP, increasing levels of cytoprotective molecules as adenosine and inosine in sedentary, overweight and physically active subjects.Support or Funding InformationNacional Council of Scientific and Technological Development (CNPq, Brazil) and Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil) supported this work.

Association between uric acid levels and cardio-renal outcomes and death in patients with type 2 diabetes: A subanalysis of EMPA-REG OUTCOME.

In the EMPA‐REG OUTCOME trial, we explored the association between pre‐randomization uric acid level tertile (<309.30 μmol/L; 309.30 to <387.21 μmol/L; ≥387.21 μmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all‐cause mortality, three‐point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 μmol/L, and patients’ baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio‐renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three‐point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89–1.67; P = 0.2088), 1.51 (95% CI 1.02–2.23; P = 0.0396) and 1.77 (95% CI 1.33–2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio‐renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required.

Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington's Patients.

Oxidative stress has long been implicated in the pathophysiology and progression of Huntington’s disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson’s disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology.

Protective effects of spirulina against hemato-biochemical alterations, nephrotoxicity, and DNA damage upon lead exposition.

The current study was aimed at exploring the protective efficacy of spirulina against the hemato-biochemical alterations and nephrotoxicity induced by lead (Pb). Female rats aged 12 weeks were treated for 4 weeks with Pb (0.344 g kg-1 bw) associated or not with spirulina (5.3 g kg-1 bw). Renal damage induced by Pb was related to a severe anemia, increases of oxidative stress-related parameters (thiobarbituric acid reactive substances (TBARS) (+29%), protein carbonyl (PCO) (+66.3%), and advanced oxidation protein product (AOPP) (+110%)), plasma lactate dehydrogenase (LDH) (+80%), creatinine and urea levels in plasma, and uric acid concentration in urine, as well as genotoxic changes (+89.3% and +60% for DNA and mRNA levels, respectively). Conversely, LDH and antioxidant enzyme activities in kidney were decreased, as well as the levels of plasma uric acid, and urinary creatinine and urea levels. Spirulina-supplemented rats exhibited normal peripheral blood and renal parameters and renal histology. It can be suggested that Arthrospira platensis alleviates damages induced by Pb, thanks to its high phenolic content and antioxidant capacity.

English

The main sources of human exposure to aluminum are found in the extensive presence of the metal in the environment and its growing industrial applications. The present study was carried out to determine the effectiveness of the Thymus vulgaris L. extract in alleviating aluminum chloride (AlCl3) toxicity on biochemical and antioxidant parameters. The experiment&rsquo;s rats were divided into five groups: a control group; an intoxicated group (300 mg AlCl3/kg bw); and three other groups which were given AlCl3 (300mg/kg/bw) then T. vulgaris. L extract (T.v), Malic Acid (MA) and Vitamin E (Vit E) at a concentration of 150mg/kg/bw. Each group was given its respective dosage, daily for 90 days. The results showed a significant decrease in the body/liver/kidney weights, the plasma total protein (T. Protein) and albumin (Alb) levels (p&le;0.05) in the intoxicated rats group. However, a significant increase in the plasma uric acid (Uac), alkaline (AlP) and acid phosphatase (AcP) levels was noted (p&le;0.05) in the same group. The amount of aluminum, TBARS and nitrate/nitrite (NO) in the liver and kidney tissues of the rats treated with AlCl3 was also found to have increased (p&le;0.05), while the levels of glutathione peroxidase (GSH-Px) and glutathione transferase (GSH-St) have decreased significantly (p&le;0.05). These altered parameters were restored in the rats treated with the T. vulgaris L. extract. Therefore, due to these beneficial effects, T. vulgaris L. could potentially be used to antagonize AlCl3 toxicity. Key words: Thymus vulgaris L., aluminum chloride, oxidative stress, malic acid, vitamin E. &nbsp;

Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway.

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Zinc alleviates maneb-induced kidney injury in adult mice through modulation of oxidative stress, genotoxicity, and histopathological changes.

Zinc is one of the important essential trace minerals to human health due to its antioxidant properties. The present study was conducted to elucidate its potential protective role against maneb-induced nephrotoxicity. For this purpose, animals were randomly divided into four groups of six each. Mice of group I (negative controls) have received daily 0.5ml of distilled water, a solvent of maneb. Mice of group II (MB) have received 30mg/kg bw of maneb daily by intraperitoneal way. Mice of group III (MB + Zn) have received the same dose of maneb as group II, along with ZnSO4 (30mg/kg bw) daily. Mice of group IV (Zn), considered as positive controls, have received the same dose of ZnSO4 as group III daily. Our results revealed that ZnSO4 co-administration to maneb-treated mice decreased kidney levels of malondialdehyde, hydrogen peroxide, protein carbonyls, and advanced oxidation protein products; the levels of non-enzymatic antioxidants like vitamin C, glutathione, and metallothionein. It recovered the alteration of antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and attenuated DNA fragmentation. Furthermore, this essential trace element was also able to alleviate kidney biomarkers' alterations by lowering plasma levels of creatinine, urea, uric acid, and lactate dehydrogenase. In addition, the histopathological changes induced by maneb were improved following zinc administration. Our results indicated that zinc might be beneficial against maneb-induced renal oxidative damage in mice.