P0168FRUCTOSE IS A CAUSE OF CALCIUM PHOSPHATE UROLITHIASIS IN RATS

Abstract Background and Aims Excessive consumption of fructose (Fr) leads to obesity, metabolic syndrome and insulin resistance, which are known risk factors for kidney stones. Along with the epidemic of obesity and diabetes there is also a growing incidence of kidney stones in both adults and children. The epidemiological studies have shown that the relative risk of nephrolithiasis significantly increases with fructose intake in diet. The aim of the study was to assess the effect of high-fructose diet on kidney tubules disorders and predisposition to the development of kidney stones. Method Male Wistar rats were assigned for 8 weeks to 3 groups differing in the content of Fr in the diet: RD - regular diet with a fructose content <3%; F10 - regular diet with an addition of 10% Fr in drinking water; F60 - 60% Fr as a solid feed. Serum concentration of Fr, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (Hcs), uric acid (UA), calcium (Ca), phosphorus (P), magnesium (Mg) were measured. Based on a 24-hour urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (UAE), phosphorus (PE), calcium (CaE), magnesium (MgE) and sodium (NaE). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using H+E and von Kossa staining. Statistical analysis was performed using one-way analysis of variance ANOVA. Statistical significance was considered as p<0,05. Results The results are presented in table as mean ± SD. The rats did not differ in total calories intake in their diet. Conclusion The high-fructose diet, in a dose-dependent manner, exacerbated inflammation and induced damage to the proximal tubules. Both F10 and F60 led to hypouricosuria, hypercalciuria and hyperphosphaturia. Those disturbances, in turn, caused precipitation of calcium phosphate deposits in kidney tubules and parenchyma.

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High-Fructose Diet Increases Inflammatory Cytokines and Alters Gut Microbiota Composition in Rats

Mediators of Inflammation ◽

10.1155/2020/6672636 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yong Wang ◽

Wentao Qi ◽

Ge Song ◽

Shaojie Pang ◽

Zhenzhen Peng ◽

...

Keyword(s):

Uric Acid ◽

Inflammatory Response ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Proinflammatory Cytokines ◽

Lipid Accumulation ◽

Fasting Blood Glucose ◽

High Fructose Diet ◽

Fructose Intake ◽

High Fructose

High-fructose diet induced changes in gut microbiota structure and function, which have been linked to inflammatory response. However, the effect of small or appropriate doses of fructose on gut microbiota and inflammatory cytokines is not fully understood. Hence, the abundance changes of gut microbiota in fructose-treated Sprague-Dawley rats were analyzed by 16S rRNA sequencing. The effects of fructose diet on metabolic disorders were evaluated by blood biochemical parameter test, histological analysis, short-chain fatty acid (SCFA) analysis, ELISA analysis, and Western blot. Rats were intragastrically administered with pure fructose at the dose of 0 (Con), 2.6 (Fru-L), 5.3 (Fru-M), and 10.5 g/kg/day (Fru-H) for 20 weeks. The results showed that there were 36.5% increase of uric acid level in the Fru-H group when compared with the Con group. The serum proinflammatory cytokines (IL-6, TNF-α, and MIP-2) were significantly increased ( P < 0.05 ), and the anti-inflammatory cytokine IL-10 was significantly decreased ( P < 0.05 ) with fructose treatment. A higher fructose intake induced lipid accumulation in the liver and inflammatory cell infiltration in the pancreas and colon and increased the abundances of Lachnospira, Parasutterella, Marvinbryantia, and Blantia in colonic contents. Fructose intake increased the expressions of lipid accumulation proteins including perilipin-1, ADRP, and Tip-47 in the colon. Moreover, the higher level intake of fructose impaired intestinal barrier function due to the decrease of the expression of tight junction proteins (ZO-1 and occludin). In summary, there were no negative effects on body weight, fasting blood glucose, gut microbiota, and SCFAs in colonic contents of rats when fructose intake is in small or appropriate doses. High intake of fructose can increase uric acid, proinflammatory cytokines, intestinal permeability, and lipid accumulation in the liver and induce inflammatory response in the pancreas and colon.

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Acute emotional stress and high fat/high fructose diet modulate brain oxidative damage through NrF2 and uric acid in rats

Nutrition Research ◽

10.1016/j.nutres.2020.05.009 ◽

2020 ◽

Vol 79 ◽

pp. 23-34

Author(s):

C. Batandier ◽

T. Poyot ◽

N. Marissal-Arvy ◽

K. Couturier ◽

F. Canini ◽

...

Keyword(s):

Uric Acid ◽

Oxidative Damage ◽

Emotional Stress ◽

High Fat ◽

High Fructose Diet ◽

Acute Emotional Stress ◽

High Fructose

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CHRONIC AEROBIC EXERCISE PREVENTS HIGH-FRUCTOSE DIET-INDUCED IMPAIRMENT IN BLOOD PRESSURE IN HEALTHY YOUNG ADULTS: A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

British Journal Of Nutrition ◽

10.1017/s0007114521004980 ◽

2021 ◽

pp. 1-41

Author(s):

Alexandra Ferreira Vieira ◽

Cesar Eduardo Jacintho Moritz ◽

Thiago Rozales Ramis ◽

Francesco Pinto Boeno ◽

Gabriela Cristina dos Santos ◽

...

Keyword(s):

Blood Pressure ◽

Young Adults ◽

Body Weight ◽

Uric Acid ◽

Aerobic Exercise ◽

Pancreatic Beta Cell ◽

Resistance Index ◽

Sensitivity Index ◽

High Fructose Diet ◽

High Fructose

Abstract The purpose of the study was to verify the effect of 4 weeks of a high-fructose diet associated with aerobic training on the risk factors for cardiometabolic diseases. Twenty-one young adults were randomized into three groups: high-fructose diet (HFD: 1 g/kg body weight of fructose/day), high-glucose diet (HGD: 1 g/kg body weight of glucose/day), and high-fructose diet and exercise (HFDE: 1 g/kg body weight of fructose/day + 3 weekly 60-minute sessions of aerobic exercise). Before and after the 4 weeks of the intervention, blood samples were taken and flow-mediated dilatation, insulin resistance index, pancreatic beta cell functional capacity index, insulin sensitivity index, and 24-hour blood pressure were evaluated. HFD showed an increase in uric acid concentrations (p = 0.040), and HGD and HFDE groups showed no changes in this outcome between pre- and post-intervention; however, the HFDE group showed increased uric acid concentrations from the middle to the end of the intervention (p = 0.013). In addition, the HFD group showed increases in nocturnal systolic blood pressure (SBP) (p = 0.022) and nocturnal diastolic blood pressure (DBP) (p = 0.009). The HGD group exhibited decreases in nocturnal SBP (p = 0.028) and nocturnal DBP (p = 0.031), and the HFDE group showed a decrease in 24-hour SBP (p = 0.018). The consumption of 1 g/kg of fructose per day can increase uric acid concentrations and blood pressure in adults. Additionally, aerobic exercises along with fructose consumption attenuate changes in uric acid concentrations and prevent impairment in nocturnal blood pressure.

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Evaluation of Antioxidant and Xanthine Oxidase Inhibitory Potential of Methanolic Leaf Extract of Stevia rebaudiana

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i59b34384 ◽

2021 ◽

pp. 302-309

Author(s):

M. Rishikesan ◽

R. Gayathri ◽

V. Vishnu Priya ◽

J. Selvaraj ◽

S. Kavitha

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Leaf Extract ◽

Statistical Significance ◽

Stevia Rebaudiana ◽

Dependent Manner ◽

Percolation Method ◽

Inhibitory Potential ◽

Dose Dependent ◽

Range Test

Background: Stevia rebaudiana is a shrub-like plant that belongs to the sunflower family and is commonly referred as stevia.It is 1000 times sweeter than sugar even at a very low concentration. Xanthine oxidase is an enzyme that generates oxygen species and catalyzes the production of uric acid from purine metabolism.Overproduction of uric acid results in a clinical condition called gout. The aim of this study is to explore the phytochemicals, antioxidant and xanthine oxidase inhibitory potential of methanolic leaf extract of stevia rebaudiana. Methods: Methanolic leaf extract of Stevia rebaudiana was prepared by the Hot Percolation method. Phytochemical screening was done to analyse the presence of various phytochemicals. The leaf extract was tested for its antioxidant and xanthine oxidase inhibitory potentials. The data were analyzed statistically by a one-way analysis of variance (ANOVA) followed by Duncan’s multiple range test was used to see the statistical significance among the groups. The results with the p<0.05 level were considered to be statistically significant. Results: It was observed that the methanolic leaf extract of Stevia rebaudiana has significant antioxidant potential (Ic50 of = 310 μg/ml) as well as xanthine oxidase inhibitory potentials(Ic50 of = 270 μg/ml) and the activity increased in a dose dependent manner as compared to that of standard (Vitamin C and Allopurinol respectively). Conclusion: The study proves the antioxidant and xanthine oxidase inhibitory efficacy of Stevia rebaudiana and throws light on the prospects of drug formation against oxidant activity and gout formation.

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Investigation of the effect of coffee on body weight, serum glucose, uric acid and lipid profile levels in male albino Wistar rats feeding on high-fructose diet

Laboratory Animal Research ◽

10.1186/s42826-019-0024-y ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 1

Author(s):

Teka Obsa Feyisa ◽

Daniel Seifu Melka ◽

Menakath Menon ◽

Wajana Lako Labisso ◽

Mezgebu Legesse Habte

Keyword(s):

Metabolic Syndrome ◽

Body Weight ◽

Uric Acid ◽

Lipid Profile ◽

Wistar Rats ◽

Serum Glucose ◽

Control Group ◽

Fasting Serum ◽

High Fructose Diet ◽

High Fructose

AbstractCoffee is one of the most commonly consumed beverages in the worldwide and is assumed to have protective effects against metabolic syndrome. The present study was aimed at investigating the effect of coffee on body weight, serum glucose, uric acid and lipid profile levels in male albino Wistar rats feeding on high fructose diet. A post-test experimental study was conducted on a total of 30 (9–10 weeks old) male albino Wistar rats. The rats were divided into 6 groups: group I (normal control)-fed on standard chow and plain tap water only; group II (fructose control)-fed on standard chow and 20% of fructose solution; group III–VI (treatment groups)-fed on standard chow, 20% of fructose solution and treated with 71, 142, 213 and 284 mg/kg body weight/day of coffee respectively for six weeks. At the end, body weight, serum glucose, uric acid and lipid profile levels were investigated. Data was entered and cleared by epi-data software version 3.1 and analyzed by one way ANOVA followed by Tukey post hoc multiple comparison tests using SPSS V. 23.00. Statistical significance was considered at p < 0.05. The results showed that body weight, fasting serum glucose and uric acid levels significantly lowered in rats treated with 213 (p = 0.047; 0.049; 0.026) and 284 (p = 0.035; 0.029; 0.010) mg/kg body weight/day of coffee compared to fructose control group. Fasting serum triglycide (TG) and low density lipoprotein (LDL-C) levels showed significant reduction in rats treated with 284 mg/kg body weight/day of coffee as compared to fructose control group (p = 0.031; 0.046) respectively. In conclusion, treating rats with coffee decreased body weight, fasting serum glucose, uric acid, TC, TG and LDL-C, and increased HDL-C in a dose dependent manner in rats feeding on high fructose diet, suggesting that coffee consumption may be helpful in ameliorating metabolic syndrome.

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Cardiometabolic Changes in Different Gonadal Female States Caused by Mild Hyperuricemia and Exposure to a High-Fructose Diet

International Journal of Endocrinology ◽

10.1155/2018/6021259 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

J. Soutelo ◽

Y. A. Samaniego ◽

M. C. Fornari ◽

C. Reyes Toso ◽

O. J. Ponzo

Keyword(s):

Uric Acid ◽

Lipid Profile ◽

Wistar Rats ◽

Female Rats ◽

Treatment Control ◽

High Fructose Diet ◽

High Fructose ◽

Metabolic Systems ◽

Female Wistar Rats ◽

Oxonic Acid

Background. The objective of this study is to observe if mild hyperuricemia and a high-fructose diet influence the cardiovascular and metabolic systems in hypogonadic female Wistar rats compared to normogonadic female rats. Methods. Fifty-six (56) adult female Wistar rats were used in the present work. Animals were divided into two groups: normogonadic (NGN) and hypogonadic (HGN). These groups were also divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Lipid profile, glycemia, uric acid, and creatinine determinations were assessed. Cardiovascular changes were evaluated by measuring blood pressure, myocyte volume, fibrosis, and intima-media aortic thickness. Results. HGN rats had higher levels of total cholesterol (TC) (p<0.01) and noHDLc (p<0.01), in addition to higher levels of uric acid (p<0.05). The OA group significantly increased myocyte volume (p<0.0001) and the percentage of fibrosis as well as the group receiving FOA (p<0.001) in both gonadal conditions, being greater in the HGN group. Hypogonadic animals presented a worse lipid profile. Conclusion. Mild hyperuricemia produces hypertension together with changes in the cardiac hypertrophy, fibrosis, and increased thickness of the intima media in hypogonadic rats fed high-fructose diet.

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P0964EFFECTS OF XANTHINE OXIDASE INHIBITORS AND DAPAGLIFLOZIN ON RENAL GLUCOSE AND URATE TRANSPORTERS IN METABOLIC SYNDROME

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa144.p0964 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Hwee-Yeong Ng ◽

Chien-Te Lee ◽

Foong-Fah Leung ◽

Yuai-Ting Lee

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Uric Acid ◽

Xanthine Oxidase ◽

Resistance Index ◽

High Fructose Diet ◽

Insulin Resistance Index ◽

Xanthine Oxidase Inhibitors ◽

High Fructose ◽

Uric Acid Transporters

Abstract Background and Aims Metabolic syndrome consists of several medical conditions that collectively predict the risk for cardiovascular disease. Hyperglycemia and hyperuricemia are the major disorders of metabolic syndrome. Kidney reabsorbs almost all filtrated glucose by active transport at normal concentrations of plasma glucose via members of the sodium glucose transport (SGLT) family. Besides, the kidney plays a pivotal role in handling uric acid homeostasis. Uric acid is mainly controlled by urate transporter (UAT), urate anion exchanger 1 (URAT1) and glucose transporter 9 (GLUT9). The aims of the study were to determine the alteration of renal glucose and uric acid transporters in animals with metabolic syndrome after treatment of xanthine oxidase inhibitors and SGLT2 inhibitor. Method Sprague-Dawley rats were fed with normal chow (Control) or high fructose diet (60%) for totally 6 months. For those animals fed with high fructose diet for 3 months, they were divided into 4 groups including high fructose diet without treatment (FR), treatment with allopurinol (150 mg/L in drinking water), with febuxostat (30 mg/L in drinking water) or with dapagliflozin (1mg/kg/day intraperitoneal injection). Blood, urine and blood pressure were collected and measured at the end of study. Gene and protein expression of renal glucose and uric acid transporters were determined by reverse transcriptase polymerase chain reaction. The changes of transporters were then confirmed by immunohistochemical staining. Results High-fructose diet induced higher levels of fasting glucose, insulin resistance index, uric acid, triglyceride and blood pressure in FR group (all p <0.05 vs. control). Treatment of allopurinol, febuxostat and dapagliflozin reduced body weight significantly. Fasting glucose, insulin resistance index and hyperuricemia were improved in all drug treatment groups (all p <0.05). In the kidney, high fructose diet significantly upregulated SGLT1, SGLT2 and GLUT2 but downregulated GLUT1 expression. Urate transporters, including GLUT9, UAT and URAT1 were also increased (p <0.05). The improvement of insulin resistance by xanthine oxidase inhibitors was associated with suppression of renal SGLT1, SGLT2 and GLUT2 expression. Dapagliflozin alleviated hyperuricemia and induced uricosuria without affecting serum xanthine oxidase activity. Compared to FR, dapagliflozin significantly inhibited fructose-induced overexpression of GLUT9, UAT and URAT1 in the kidney. Conclusion Long term high fructose diet induced metabolic syndrome in rats. Treatment of xanthine oxidase inhibitors and dapagliflozin ameliorated components of metabolic syndrome. Both allopurinol and febuxostat improved insulin resistance in association with suppression of renal SGLT1, SGLT2 and GLUT2 expression. Although dapagliflozin and xanthine oxidase inhibitors reduced uric acid in different mechanisms, they shared a similar molecular changes in the kidney by downregulating GLUT9, UAT and URAT1 expression.

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Effect of Eucommia ulmoides leaves on hyperuricemia and kidney injury induced by a high-fat/high-fructose diet in rats

10.21203/rs.3.rs-1188416/v1 ◽

2021 ◽

Author(s):

Man Gong ◽

Hong Zhang ◽

Xiaoqian Liu ◽

Qingxia Li ◽

Yang Zhang ◽

...

Keyword(s):

Uric Acid ◽

Molecular Docking ◽

Renal Injury ◽

Endocrine Resistance ◽

Network Pharmacology ◽

Eucommia Ulmoides ◽

High Fat ◽

Protein Database ◽

High Fructose Diet ◽

High Fructose

Abstract Eucommia ulmoides leaves have unique advantages in the treatment of metabolic diseases. In this study, network pharmacology and molecular-docking methods were used to predict the effects and action mechanisms of the major components of E. ulmoides leaves on hyperuricemia. Combining literature collection, we used SciFinder and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to collect E. ulmoides leaf flavonoid and iridoid components. Swiss Target Prediction, SEA, GeneCards, and the OMIM database were used to obtain core targets, and the STRING protein database was performed as core targets for gene ontology enrichment Set and KEGG analyses. Molecular docking was applied to predict the pathways regulating the metabolism of uric acid. The selected targets and targeting efficacy were validated using a rat model of hyperuricemia and renal injury induced by a high-fat and high-fructose diet. A total of 32 chemical components with effective targets, which regulated the PI3K-AKT pathway and endocrine resistance, were collected. Isoquercetin, kaempferol, and quercetin were predicted via network pharmacology to have potential bioactivities and strong docking binding forces. Molecular docking results showed that iridoids and flavonoids are bound to proteins related to inflammation and uric acid metabolism. In addition, it was verified via animal experiments that an E. ulmoides leaf extract ameliorated hyperuricemia, renal injury, and inflammation, which are closely related to the targets IL-6, TNF-α, TLR4, and GLUT9. In conclusion, E. ulmoides leaf flavonoids and iridoids ameliorate hyperuricemia and uric-acid–induced inflammation through a multi-component, multi-target, and multi-pathway mechanism, which provides a theoretical basis for the development of therapeutics from E. ulmoides leaf components.

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Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet

BMC Genomics ◽

10.1186/s12864-021-08166-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Laura A. Cox ◽

Jeannie Chan ◽

Prahlad Rao ◽

Zeeshan Hamid ◽

Jeremy P. Glenn ◽

...

Keyword(s):

Regulatory Network ◽

Molecular Mechanisms ◽

Statistical Significance ◽

Molecular Networks ◽

Integrated Analysis ◽

Chow Diet ◽

Vervet Monkeys ◽

Omics Data ◽

Obesity And Diabetes ◽

High Fructose

Abstract Background Dietary high fructose (HFr) is a known metabolic disruptor contributing to development of obesity and diabetes in Western societies. Initial molecular changes from exposure to HFr on liver metabolism may be essential to understand the perturbations leading to insulin resistance and abnormalities in lipid and carbohydrate metabolism. We studied vervet monkeys (Clorocebus aethiops sabaeus) fed a HFr (n=5) or chow diet (n=5) for 6 weeks, and obtained clinical measures of liver function, blood insulin, cholesterol and triglycerides. In addition, we performed untargeted global transcriptomics, proteomics, and metabolomics analyses on liver biopsies to determine the molecular impact of a HFr diet on coordinated pathways and networks that differed by diet. Results We show that integration of omics data sets improved statistical significance for some pathways and networks, and decreased significance for others, suggesting that multiple omics datasets enhance confidence in relevant pathway and network identification. Specifically, we found that sirtuin signaling and a peroxisome proliferator activated receptor alpha (PPARA) regulatory network were significantly altered in hepatic response to HFr. Integration of metabolomics and miRNAs data further strengthened our findings. Conclusions Our integrated analysis of three types of omics data with pathway and regulatory network analysis demonstrates the usefulness of this approach for discovery of molecular networks central to a biological response. In addition, metabolites aspartic acid and docosahexaenoic acid (DHA), protein ATG3, and genes ATG7, and HMGCS2 link sirtuin signaling and the PPARA network suggesting molecular mechanisms for altered hepatic gluconeogenesis from consumption of a HFr diet.

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