scholarly journals Uricase deficiency causes mild and multiple organ injuries in rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256594
Author(s):  
Nan Fan ◽  
Yun Yu ◽  
Lvyu Li ◽  
Heng Xia ◽  
Xiangxian Dong ◽  
...  
Keyword(s):  
Body Weight ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Weight Ratio ◽  
Young Male ◽  
Multiple Organ ◽  
Male Rats ◽  
Wild Type ◽  
Subsequent Increase ◽  
Wild Type Male

Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between uricase-deficient (Kunming-DY rats) and wild-type male rats. Uricase-deficient rats and wild-type rats were commonly bred. Their body weight, water and food consumption, 24-h urine and feces, uric acid in serum and organs, and serum indexes were recorded or assayed. Organs, including the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum, were examined using a routine hematoxylin-eosin staining assay. We found that the growth of male uricase-deficient rats was retarded. These rats excreted more urine than the wild-type rats. Their organ indexes (organ weight body weight ratio), of the heart, liver, kidney, and thymus significantly increased, while those of the stomach and small intestine significantly decreased. The uricase-deficient rats had a significantly higher level of serum uric acid and excreted more uric acid via urine at a higher concentration. Except for the liver, uric acid increased in organs and intestinal juice of uricase-deficient rats. Histological examination of the uricase-deficient rats showed mild injuries to the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum. Our results suggest that uricase-deficient rats have a different biological pattern from the wild-type rats. Uricase deficiency causes growth retardation of young male rats and the subsequent increase in serum uric acid results in mild organs injuries, especially in the kidney and liver.

Construction of Hyperuricemia Model Rats with Yeast Extract Combined with Oteracil Potassium

2020 ◽  
Author(s):  
Dilidaer Xilifu ◽  
Alimu Kateer ◽  
Nijiati Rehemu ◽  
Zhao-yong Li ◽  
jie Jiang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Yeast Extract ◽  
Intraperitoneal Injection ◽  
Rat Kidney ◽  
Optimal Dose ◽  
Serum Levels ◽  
Male Rats ◽  
Control Group ◽  
Optimal Dosage

Abstract Background: Hyperuricemia is the most important risk factor for gout, hypertension, coronary artery disease and other cardiovascular diseases. The incidence of hyperuricemia gradually increased in recent years and it is very necessary to explore the medications of the prevention and treatment of hyperuricemia using hyperuricemia animal models. Objective: The objective of present study is to explore the optimal dose of yeast extract and oteracil potassium in the establishment of hyperuricemia rat model. Method: Sixty-four male rats were randomly divided into 8 experimental groups. Rats were treated with yeast extract by intraperitoneal injection or yeast extract by intraperitoneal injection combined with various doses of oteracil potassium by intragastric feeding or intraperitoneal injection for 28 days. The serum uric acid, urea nitrogen and creatinine levels of different groups were measured at 0th day, 7th day, 14th day, 21th day and 28th day. Results: The serum levels of uric acid in the groups of intraperitoneal injection with yeast extract alone, yeast extract by intraperitoneal injection combined with 50-200 mg/kg oteracil potassium by intragastric feeding and yeast extract by intraperitoneal injection combined with 50-100 mg/kg oteracil potassium by intraperitoneal injection were higher than that in the control group. But we found no significant effect on rat kidney, heart or artery in the above groups. In the group of yeast extract by intraperitoneal injection combined with 200 mg/kg oteracil potassium by intraperitoneal injection, we observed the significantly high level of serum uric acid and morphological and pathological changes in rat kidney, heart and artery. Conclusion: In the present study, we found that continuously treated with yeast extract combined with oteracil potassium is an effective method to establish rat hyperuricemia model. Intraperitoneal injection of yeast extract combined with 200 mg/kg oteracil potassium is an optimal dosage for the construction of a persistent and stable hyperuricemia animal model.

FACTORS INFLUENCING THE EXCRETION OF A FAT-MOBILIZING SUBSTANCE IN THE URINE OF RATS

1966 ◽  
Vol 44 (1) ◽  
pp. 95-101 ◽  
Author(s):  
J. R. Beaton ◽  
A. J. Szlavko ◽  
J. A. F. Stevenson
Keyword(s):  
Body Weight ◽  
Sex Difference ◽  
Specific Activity ◽  
Young Male ◽  
Total Activity ◽  
Female Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Adult Rats ◽  
Factors Influencing

The effect of various factors on excretion of a lipid-mobilizing activity in FMS IA (anorexigenic) and in FMS IB (fat-mobilizing) by the fasting rat has been investigated. During fasting, the greatest excretion of such activity in FMS IA and FMS IB occurred in the first 24 hours and diminished thereafter up to 72 hours; and the specific activity of FMS IB was greatest in the first 24 hours whereas that of FMS IA was constant throughout. The hypothalamicobese rat excretes FMS IA and FMS IB in greater than normal amounts. The alloxan-diabetic rat excretes less total activity of FMS IA and IB than do control animals. Young male rats excrete greater amounts of FMS IB, but not of FMS IA, than do adult rats, the greatest excretion per 100 g body weight being observed at approximately 37 days of age. At 27 days of age (prepuberty), male rats excreted a greater total activity of FMS IB but not of FMS IA than did female rats. At 90 days of age (post-puberty), there was no apparent sex difference in the amount of total activity of FMS IB excreted per rat, but when expressed per 100 g body weight, females excreted more FMS IB than did males.

BODY-WEIGHT, ABO BLOOD-GROUPS, AND ALTITUDE AS DETERMINANTS OF SERUM-URIC-ACID

The Lancet ◽  
1969 ◽  
Vol 294 (7627) ◽  
pp. 963
Author(s):  
RoyM. Acheson ◽  
Charles Du V. Florey
Keyword(s):  
Body Weight ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Blood Groups ◽  
Abo Blood Groups

Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats

2000 ◽  
Vol 19 (3) ◽  
pp. 185-192 ◽  
Author(s):  
B I Ghanayem ◽  
S M Ward ◽  
B Chanas ◽  
A Nyska
Keyword(s):  
Body Weight ◽  
Cell Volume ◽  
Weight Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mean Cell Volume ◽  
Male And Female ◽  
Male And Female Rats ◽  
Butoxyacetic Acid ◽  
F344 Rats

Administration of 2-butoxyethanol (BE) to rodents causes acute hemolytic anemia, and metabolic activation of BE to butoxyacetic acid (BAA) is required for the development of this effect. Recent studies have shown that female rats treated with BE exhibit a variety of histopathologic lesions that are absent in males and many of these lesions are attributed to the hemolytic effects of BE. Current studies were designed to compare the acute hematotoxicity of BE in male and female F344 rats. Rats were treated with 250 mg BE/kg body weight or water (control; 5 ml/kg) by gavage. At 4, 8, or 24 h after dosing, rats were anesthetized, blood was collected by cardiac puncture, and various blood parameters were measured. BE resulted in a time-dependent swelling of erythrocytes as evidenced by an early increase in hematocrit (Hct) and mean cell volume (MCV) in male rats. In contrast, increased Hct in female rats did not accompany an increase in MCV. It is likely that hemolysis was so severe at 4 h that Hct exhibited a decline in female rats at that time point. Subsequently, red blood cell (RBCs), hemoglobin concentration (Hgb), and Hct declined as hemolysis progressed. However, the onset of BE-induced hemolysis was faster in female compared to male rats. These effects were also associated with a significant increase in the spleen weight to body weight ratio. Blood smears were also prepared and morphological changes evaluated by light microscopy included stomatocytosis, spherocytosis, and schistocytosis. Furthermore, aggregation of RBCs in female rats as evidenced by increased formation of rouleaux was observed at 24 h after BE administration. These effects were observed earlier and more frequently in female rats. No differences in the sensitivity of RBCs obtained from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was observed as determined by measuring the packed cell volume. In conclusion, these data suggest that female rats are more sensitive to hemolysis and morphological alterations of erythrocytes induced by BE during the first 24 h after exposure compared to males. It is likely that the greater sensitivity of female rats to BE effects on RBCs may account for the reported development of thrombosis and tissue infarction in female rats.

scholarly journals Investigating the Role of Farnesoid X Receptor in Heme Biosynthesis and Ductular Reaction

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A810-A811
Author(s):  
Angela E Dean ◽  
Emilian Jungwirth ◽  
Katrin Panzitt ◽  
Martin Wagner ◽  
Sayeepriyadarshini Anakk
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Weight Ratio ◽  
Heme Biosynthesis ◽  
Farnesoid X Receptor ◽  
Whole Body ◽  
Wild Type ◽  
Body Weight Ratio ◽  
Ductular Reaction ◽  
Male And Female

Abstract Bile acids (BAs) have gained traction not just as emulsifiers of fat, but also as hormones. Nuclear receptor Farnesoid X receptor (FXR) is the master regulator of BAs and can also control glucose and lipid metabolism. We examined if FXR contributed towards heme biosynthesis and induction of a ductular reaction. Male and female whole body Fxr knockout (FxrKO) mice, as well as liver- and intestine-specific knockouts (LFxrKO and IFxrKO, respectively) were treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC, a ferrochelatase inhibitor) for two weeks. At the end of the two weeks, mice were fasted for four hours and euthanized. All groups of mice had lost a similar percentage of body weight when fed the DDC diet. However, female FxrKO mice had significantly increased liver to body weight ratio, while male FxrKO mice had significantly decreased liver to body weight ratio when fed the DDC diet compared with their wild type counterparts. Serum liver injury markers were analyzed and liver histology and changes in genes involved in the heme biosynthesis pathway were examined. Both male and female whole body FxrKO livers had decreased ductular reaction with minimal bile plugs (porphyrin accumulation) compared with their wild type counterparts. LFxrKO mice mimicked diminished ductular reaction, while IFxrKO mice exhibited severe ductular reaction similar to that of wild type mice, indicating that the ductular reaction is dependent on hepatic FXR. ChIP-Seq for FXR revealed binding peaks in the heme biosynthesis genes, Alas1, Alad, Uros, and Fech, suggesting that FXR may act as a transcription factor for these genes. Further investigation revealed that Pbgd gene expression was increased, while Fech gene expression was decreased in female FxrKO mice compared to wild type mice. In male mice, Pbgd, Uros, Urod, and Cpox gene expression was increased in the absence of Fxr. In conclusion, Fxr is necessary to mount a ductular reaction and plays a key role in heme biosynthesis in the liver.

scholarly journals Mediators of the effect of ertugliflozin on a composite kidney outcome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: analyses from VERTIS CV

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
D Z I Cherney ◽  
M Segar ◽  
A Pandey ◽  
C P Cannon ◽  
F Cosentino ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Body Weight ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Atherosclerotic Cardiovascular Disease ◽  
Composite Outcome ◽  
Average Change ◽  
Post Randomisation

Abstract Introduction Sodium–glucose cotransporter 2 (SGLT2) inhibitors have been shown to slow the decline of kidney function in outcome trials, but the biological mediator(s) underlying the therapeutic benefit are not well established. Purpose We performed a post-hoc analysis exploring potential mediators of the effects of the SGLT2 inhibitor ertugliflozin on the VERTIS CV exploratory kidney composite outcome (sustained 40% decrease from baseline in estimated glomerular filtration rate [eGFR], chronic kidney replacement therapy or kidney death). Methods In VERTIS CV, 8246 participants with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomised to placebo, ertugliflozin 5 mg or 15 mg (pooled for analyses, as prospectively planned), and were followed for a mean of 3.5 years. The hazard ratio (HR; 95% confidence interval) for the pre-specified exploratory kidney composite outcome was 0.66 (0.50, 0.88). Cox regression models were used to evaluate covariates that were significantly differentially changed from baseline with ertugliflozin treatment as candidate mediators, with a mediator identified as a covariate when added to an unadjusted model of randomised treatment assignment a) yielded a larger hazard ratio; and b) the mediator retained P<0.05 in the model (eGFR was excluded as a covariate). The percentage of mediation was determined by the proportional increase in the HR between the unadjusted and adjusted models for each post-randomisation period: early (first change from baseline measurement) and average (weighted average of change from baseline from all post-baseline measurements). Each potential mediator was tested individually, so across analyses, mediation % sums to >100%. Results Of 22 covariates significantly changed by ertugliflozin, nine were identified as potential mediators (Table). The covariates with a high percentage of mediation were those related to changes in blood erythrocytes (haemoglobin, haematocrit and red blood cell mass), with average changes in haemoglobin having the highest percentage of mediation (61.8%). Serum uric acid was associated with a mediation of 29.4% and 50.0% for the early and average post-randomisation effect periods, respectively. Early changes in glycated haemoglobin had a large mediation (50%), but the average change during the trial was not significant. Average change in serum albumin had a large mediation (29.4%). Average changes in body weight and systolic blood pressure had percentages of mediation of 41.2% and 14.7%, respectively. Conclusion Multiple factors may be involved in the reduction of the kidney composite outcome observed with ertugliflozin. In the short-term, changes in glycaemia had a high mediation effect. Over the long-term, changes suggestive of haemoconcentration and/or haematopoiesis (natriuresis-related effects), showed the highest percentage of mediation, followed by changes in serum uric acid and body weight (glucosuria-related effects). FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with Pfizer Inc., New York, NY, USA

STUDIES ON ALDOSTERONE: III. CHRONIC EFFECT ON THE BLOOD PRESSURE OF RATS

1960 ◽  
Vol 38 (1) ◽  
pp. 43-50 ◽  
Author(s):  
A. G. Gornall ◽  
H. M. Grundy ◽  
C. J. Koladich
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Protective Effect ◽  
Systolic Blood Pressure ◽  
Low Dose ◽  
Aqueous Ethanol ◽  
Young Male ◽  
Male Rats ◽  
Chronic Effect ◽  
Dose Levels

A rise in systolic blood pressure due to the administration of 0.4 or 0.5 μg of aldosterone per 100 g body weight to young male rats, over a period of 3 to 6 months, has been confirmed in two separate experiments. This effect was observed whether the aldosterone was given 3 days a week or 6 days a week, and whether dissolved in aqueous ethanol or in oil. Equal doses of 9-α-fluorohydrocortisone and of 2-methyl-9-α-fluorohydrocortisone produced similar though somewhat less consistent effects. When 4 or 5 μg of reserpine was administered along with aldosterone there was no clear evidence of a protective effect. Reserpine alone at these low dose levels was somewhat toxic in the rat and led to a rise in blood pressure.

scholarly journals The Effect of Sodium Channel Blocker, Mexiletine, on Body Weight in Type 2 Diabetes Patients with Visceral Obesity

2019 ◽  
Vol 12 ◽  
pp. 117955141882504
Author(s):  
Naohiko Ueno
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Uric Acid ◽  
Waist Circumference ◽  
Diabetic Neuropathy ◽  
Serum Uric Acid ◽  
Visceral Obesity ◽  
Control Group ◽  
Diabetes Patients

Objective: Mexiletine is an anti-arrhythmic agent also used for the treatment of painful diabetic neuropathy. In this study, the effect of mexiletine on body weight was evaluated in type 2 diabetes patients with diabetic neuropathy exhibiting visceral obesity. Methods: Type 2 diabetes patients with neuropathy exhibiting visceral obesity (n = 21) treated by mexiletine (300 mg/day) and a control group of type 2 diabetes patients with the same condition who received vitamin B12 (n = 12) were retrospectively evaluated. Body weight, waist circumference, hemoglobin A1c (HbA1c), blood pressure, liver function, serum lipids, and serum uric acid were assessed before and 6 months after the treatment. Results: Mexiletine significantly decreased body weight and waist circumference. The changes in body weight and waist circumference in 6 months in the mexiletine group were greater than in the control group. In metabolic parameters, there were significant decreases in triglyceride (TG) and serum uric acid. There were positive relationships between the change in body weight and the changes in TG, uric acid, alanine aminotransferase (ALT), and HbA1c. Conclusions: Mexiletine may affect body weight regulation. It ameliorated the metabolic parameters possibly by decreasing visceral fat. Further study should be performed to clarify the mechanism of the effect.

COMPARATIVE EFFECTS OF SUCROSE AND CORNSTARCH IN LOW-PROTEIN DIETS FED TO RATS EXPOSED TO COLD

1965 ◽  
Vol 43 (2) ◽  
pp. 241-249
Author(s):  
J. R. Beaton ◽  
J. F. Sangster
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Young Male ◽  
Male Rats ◽  
Low Protein ◽  
Environmental Temperatures ◽  
Protein Diets ◽  
Starch Diet

Young male rats were fed one of three low-protein (5% casein) diets differing in the source of carbohydrate (sucrose, equal parts sucrose and cornstarch, or cornstarch) or a 20% casein (sucrose) diet at environmental temperatures of 24 °C or 5 °C. Replacement of sucrose with starch appeared to have a small but significant effect in increasing body weight gain for 15 days (but not the next 28 days) at 24 °C and also in animals exposed to cold for 28 days after a 15-day feeding period at 24 °C. In disagreement with results reported by Andik et al., cold exposure, although significantly increasing body weight gain and food intake in rats fed the 5% casein – starch diet, did not elicit a weight gain as great as that observed in 20% casein-fed animals at either 24 °C or 5 °C. The 24-hour food intake following a 24-hour fast exceeded the intake on the day before fasting on all diets for animals maintained at 5 °C but not 24 °C. The immediate ([Formula: see text] hour) and 24-hour food intakes of rats at 5 °C exceeded those of comparable dietary groups at 24 °C. At 5 °C, the 24-hour food intake, following the fast, of rats fed the 5% casein – starch diet exceeded that of the 20% casein-fed controls.

Stimulation of Renal Organic Base Transport by Uranyl Nitrate

1972 ◽  
Vol 50 (6) ◽  
pp. 533-538 ◽  
Author(s):  
G. H. Hirsch
Keyword(s):  
Body Weight ◽  
Uranyl Nitrate ◽  
Weight Ratio ◽  
Male Rats ◽  
Organic Base ◽  
Body Weight Ratio ◽  
Kidney Weight ◽  
Nitrate Treatment ◽  
Cortical Slices ◽  
Stimulation Of

Administration of 6 mg/kg uranyl nitrate to adult male rats resulted in a significant enhancement of N-methylnicotinamide (NMN) uptake by renal cortical slices when measured 24 or 48 h after injection. The accumulation of another organic base, tetraethylammonium (TEA), by renal cortical slices was also significantly increased by uranyl nitrate treatment, but transport of the organic acid p-aminohippurate (PAH) was not altered in these experiments. The kidney weight to body weight ratio was increased in treated rats. Accumulation of NMN by renal cortical slices was significantly enhanced within 8 h after administration of 6 mg/kg uranyl nitrate. NMN uptake was also significantly enhanced 24 and 48 h after administration of 0.5 or 1.0 mg/kg uranyl nitrate to rats. The nephrotoxicity produced by uranyl nitrate was not directly related to its induction of organic base transport. The data support the hypothesis that the organic base transport system can be selectively induced by appropriate stimuli. Treatment of rats with potassium chloride did not enhance NMN uptake by renal cortical slices.

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