Effect of acarbose on the increased plasma concentration of uric acid induced by sucrose ingestion

Sucrose is converted fructose and glucose, which may increase plasma uric acid concentration (pUA) through increased purine degradation and/or decreased uric acid (UA) excretion. To investigate effects of acarbose, an inhibitor of alpha-glucosidase, on the increased pUA from sucrose administration, we measured pUA and urinary UA excretion in 6 healthy subjects before and after administering sucrose, with and without co-administration of acarbose. Sucrose raised pUA by 10% (p < 0.01). However, excretion and fractional clearance of UA were unchanged. Sucrose and acarbose coadministration also increased pUA, but less than did sucrose alone (sucrose: 4.9 to 5.4 mg/dl; sucrose + acarbose, 4.7 to 4.9 mg/dl, p < 0.05) without changes in urinary excretion and fractional clearance of UA. Acarbose appears to attenuate the rise in pUA by sucrose ingestion by inhibiting sucrose absorption.     

Effect of Acarbose on the Increased Plasma Concentration of Uric Acid Induced by Sucrose Ingestion

Sucrose is converted fructose and glucose, which may increase plasma uric acid concentration (pUA) through increased purine degradation and/or decreased uric acid (UA) excretion. To investigate effects of acarbose, an inhibitor of alpha-glucosidase, on the increased pUA from sucrose administration, we measured pUA and urinary UA excretion in 6 healthy subjects before and after administering sucrose, with and without co-administration of acarbose. Sucrose raised pUA by 10% (p < 0.01). However, excretion and fractional clearance of UA were unchanged. Sucrose and acarbose coadministration also increased pUA, but less than did sucrose alone (sucrose: 4.9 to 5.4 mg/dl; sucrose + acarbose, 4.7 to 4.9 mg/dl, p < 0.05) without changes in urinary excretion and fractional clearance of UA. Acarbose appears to attenuate the rise in pUA by sucrose ingestion by inhibiting sucrose absorption.     

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation

BackgroundA high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified.MethodsWe used male Wistar rats, which were orally administered fructose (5 g/kg). Those rats were used in each experiment at 12 h after administration.ResultsSingle administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose.ConclusionsSingle administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia.     

Effects of allopurinol on beer-induced increases in plasma concentrations and urinary excretion of purine bases (uric acid, hypoxanthine, and xanthine).

To determine the effects of allopurinol on beer-induced increases in plasma and urinary excretion of purine bases (hypoxanthine, xanthine, and uric acid), we performed three experiments on five healthy study participants. In the first experiment (combination study), the participants ingested beer (10 ml/kg body weight) eleven hours after taking allopurinol (300 mg). In the second experiment (beer-only study), the same participants ingested beer (10 ml/kg body weight) alone, while in the third experiment (allopurinol-only study), they took allopurinol (300 mg) alone. There was a two-week interval between each of the studies. Beer-induced increases in plasma concentration and urinary excretion of hypoxanthine in the combination study were markedly higher than those in the beer-only study. On the other hand, the sum of increases in plasma concentrations of purine bases in the beer-only study was greater than in the combination study, whereas the increase in plasma uridine concentration in the combination study did not differ from the beer-only study. In addition, allopurinol administration inhibited the beer-induced increase in plasma concentration of uric acid. These results suggest that abrupt adenine nucleotide degradation may increase plasma concentration and urinary excretion of hypoxanthine under conditions of low xanthine dehydrogenase activity, which is mostly ascribable to allopurinol. Further, the difference in the sum of increases in plasma concentrations of purine bases between the combination study and beer-only study was largely ascribable to a greater increase in urinary excretion of hypoxanthine in the combination study. In addition, allopurinol intake seems to be effective in controlling the rapid increase in plasma uric acid caused by ingestion of alcoholic beverages.     

Effects of long-term beer ingestion on plasma concentrations and urinary excretion of purine bases.

To investigate the long-term effects of beer ingestion on plasma concentrations of purine bases (hypoxanthine, xanthine, and uric acid), ten healthy males ingested beer (15 ml/kg body weight) every evening for three months. Blood and 24-hour urine samples were collected in the morning on one day before and one, two, and three months after starting the experiment to determine the plasma concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine. Plasma concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine in five of the participants that did not regularly ingest beer at a quantity of more than 15 ml/kg body weight in a single day prior to the experiment were not increased during the experimental period. In contrast, plasma concentrations and urinary excretion of uric acid were increased in five participants who regularly ingested more than 15 ml/kg body weight of beer in a single day prior to the experiment, although hypoxanthine and xanthine levels were not significantly increased during the experimental period. In both groups, uric acid clearance and purine ingestion were not significantly different throughout the study. Our results suggest that the production of uric acid caused by ethanol ingestion from beer is a significant contributor to the increase in plasma uric acid concentration in patients that regularly consume more than 15 ml/kg body weight of beer each day. Therefore, patients with gout should be encouraged to refrain from drinking large amounts of beer on a daily basis.     

Effect of purine-free low-malt liquor (happo-shu) on the plasma concentrations and urinary excretion of purine bases and uridine--comparison between purine-free and regular happo-shu.

To determine whether purine-free and regular low-malt liquor beverages (happo-shu) increase the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) and uridine, 6 healthy males were given regular (10 ml/kg of body weight) and purine-free happo-shu (10 ml/kg of body weight). Plasma concentration-time curves were plotted, and the areas under the curves for uric acid and total purine bases (the sum of hypoxanthine, xanthine, and uric acid) were greater in the regular than in the purine-free happo-shu ingestion experiment (both p < 0.05). In addition, the total urinary excretion of xanthine, total purine bases, and uridine was greater in the regular than in the purine-free happo-shu ingestion experiment (p < 0.05 in all cases), although the total urinary excretion of hypoxanthine and uric acid was no different between the regular and the purine-free happo-shu ingestion experiments. These results suggest that uridine contained in regular happo-shu might contribute to an increase in the urinary excretion of uridine along with ethanol, and that the purines contained in regular happo-shu may contribute to the increase in plasma concentration of uric acid due to purine degradation.     

Effect of Beer Ingestion on the Plasma Concentrations and Urinary Excretion of Purine Bases: One-Month Study

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.     

Effect of beer ingestion on the plasma concentrations and urinary excretion of purine bases: one-month study

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.     

Depression of glutamine-stimulated uric acid production and blood glutamine accumulation by insulin in chickens

This experiment was conducted to examine effects of insulin on glutamine accumulation in blood and uric acid production in the chicken infused with glutamine. Insulin pretreatment eliminated the stimulatory effect of glutamine infusion on urinary uric acid excretion in the chicken fed a 5% protein diet, which resulted in no increase in urinary total nitrogen excretion by the infusion. In the chicken fed a 20% protein diet the pretreatment with insulin did not have such clear depressive effects on the increases in urinary uric acid and total nitrogen excretion caused by the glutamine infusion. Insulin tended to depress the increases in plasma glutamine concentration caused by the infusion of glutamine at both levels of dietary protein intake.     

Analysis of uric acid and oxypurines in normal subjects and in gout patients

The behavior of plasma and urine oxypurines (hypoxanthine and xanthine) and of uric acid has been studied in normal subjects and in gout patients. Oxypurines and uric acid were increased in the plasma of gout patients but only the urinary excretion of hypoxanthine was higher in this group. The interpretation of the observed variations is discussed.     

Effect of vitamin E therapy on serum uric acid in DOCA-salt-treated rats

Uric acid is considered as an antioxidant in the blood. Despite its proposed protective properties, elevated plasma uric acid has been associated with hypertension in a variety of disorders. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure and the changes in serum uric acid, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats. Blood pressure was monitored by tail-cuff method, urinary and plasma uric acid was measured by autoanalyzer during the induction of hypertension in 1-, 2-, 3- and 4-week DOCA-salt-treated Sprague-Dawley rats. Vitamin E (200 mg/kg/day/gavage) was co-administered with DOCA-salt for 4 weeks. From the first week of DOCA-salt treatment, rats exhibited marked increases in blood pressure. DOCA-salt treatment also resulted in a significant increase in serum uric acid and a significant decrease in urinary uric acid at the end of the first week. These changes in serum and urinary uric acid remained until the 4th week of DOCA-salt treatment but blood pressure continued to increase throughout the study. Vitamin E treatment increased urinary excretion of uric acid and decreased blood pressure and serum uric acid in DOCA-salt-treated rats. These data suggest that enhanced serum uric acid may be a contributing factor to the onset of hypertension in DOCA-salt-treated rats. A uricosuric effect is suggested for vitamin E in the treatment of hypertension.     

Effects of allopurinol on beer-induced increases in plasma concentrations of purine bases and uridine

We investigated the effects of allopurinol on beer-induced changes in the plasma concentration and urinary excretion of purine bases. Five healthy subjects underwent three studies: ingestion of beer after taking 300 mg allopurinol (combination study); ingestion of beer alone; ingestion of allopurinol alone. Increased plasma concentrations and urinary excretion of hypoxanthine were greater in the combination study than the beer alone study. However, increases in total plasma purine base concentrations were greater in the beer alone study, even though increases in plasma uridine concentrations did not differ. Beer-induced increases in plasma concentrations of purine bases appear partially offset by increased urinary excretion of hypoxanthine after allopurinol, which also controls increases in plasma uric acid levels caused by alcoholic beverage ingestion.     

Effects of Allopurinol on Beer-Induced Increases in Plasma Concentrations of Purine Bases and Uridine

We investigated the effects of allopurinol on beer-induced changes in the plasma concentration and urinary excretion of purine bases. Five healthy subjects underwent three studies: ingestion of beer after taking 300 mg allopurinol (combination study); ingestion of beer alone; ingestion of allopurinol alone. Increased plasma concentrations and urinary excretion of hypoxanthine were greater in the combination study than the beer alone study. However, increases in total plasma purine base concentrations were greater in the beer alone study, even though increases in plasma uridine concentrations did not differ. Beer-induced increases in plasma concentrations of purine bases appear partially offset by increased urinary excretion of hypoxanthine after allopurinol, which also controls increases in plasma uric acid levels caused by alcoholic beverage ingestion.     

Effect of allyl isothiocyanate on plasma and urinary concentrations of some biochemical entities in the rat.

Allyl isothiocyanate (AITC) is a constituent of several plants of the family Cruciferae that are commonly used as food. This study investigated the effect of feeding AITC to male Sprague-Dawley rats on their plasma glucose and uric acid levels as well as on the urinary concentrations of glucose, 17-ketosteroids (17-KS), creatinine, and uric acid. Other test compounds included were thyroxine (T4) and thiouracil (TU). AITC caused a highly significant (P smaller than or equal to 0.01) depression in the plasma glucose and uric acid levels compared with the control. TU caused a significant depression only of the plasma glucose. T4, on the other hand, significantly increased the levels of both glucose and uric acid. The AITC-treated rats voided twice as much urine as the controls or those receiving TU or injected with T4. The 24-h excretion of glucose, uric acid, and creatinine was significantly (P smaller than or equal to 0.01) higher in animals fed AITC than in those consuming the control diet, while the excretion of 17-KS was significantly lower. Results on an equal urine volume basis showed that differences in the excretion of glucose and creatinine were related to differences in the urine volume. TU significantly depressed excretion of all the compounds but glucose. The effect of T4 on the excretion of 17-KS and uric acid resembled that of AITC and TU, thus showing that these compounds depressed the androgenic function of the animal.     

Effects of profuse sweating induced by exercise on urinary uric acid excretion in a hot environment

In order to determine whether exercise-induced profuse sweating could reduce urinary uric acid excretion, we simulated badminton players training and measured their uric acid in urine, sweat and blood during the training period. Thirteen male volunteers who were well-trained badminton players were recruited in this study. On the first 2 days and the last 2 days of the study period none of the subjects engaged in any intense exercise- or activity-inducing profuse sweat, but they accepted routine training 2 h per day during the middle 3 days. The results show that mean serum urate levels of thirteen volunteers rose significantly on day 4, when the concentrations increased by 18.2% over day 2 (P < 0.05). The mean ten-hour urinary uric acid excretion of seven volunteers on the 3 training days was significantly less at 178.5 micromol/day and 118.3 micromol/day than those on the preceding and subsequent days of the training days, respectively (P < 0.05). Furthermore, for six volunteers, the mean ratio of clearance of uric acid to creatinine was 6.6% on day 2, which significantly decreased to 5.4% on day 4 (P < 0.05). It is concluded profuse sweating exercise results in a decrease of urinary uric acid excretion amounts and leads to increased serum uric acid after the exercise. We suggest that persons who take vigorous exercise or are exposed to hot environments need drinking enough fluids to prevent dehydration and maintain adequate urinary output. People with profuse sweat after rigorous exercise are recommended taking sports drinks containing abundant sodium in order to decrease serum uric acid.     

SGLT5 Reabsorbs Fructose in the Kidney but Its Deficiency Paradoxically Exacerbates Hepatic Steatosis Induced by Fructose

Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mice lacking the gene encoding SGLT5. Sodium-dependent fructose uptake disappeared in renal brush border membrane vesicles from SGLT5-deficient mice, and the increased urinary fructose in SGLT5-deficient mice indicated that SGLT5 was the major fructose reabsorption transporter in the kidney. From this, we hypothesized that urinary fructose excretion induced by SGLT5 deficiency would ameliorate fructose-induced hepatic steatosis. To test this hypothesis we compared SGLT5-deficient mice with wild-type mice under conditions of long-term fructose consumption. Paradoxically, however, fructose-induced hepatic steatosis was exacerbated in the SGLT5-deficient mice, and the massive urinary fructose excretion was accompanied by reduced levels of plasma triglycerides and epididymal fat but fasting hyperinsulinemia compared with fructose-fed wild-type mice. There was no difference in food consumption, water intake, or plasma fructose between the two types of mice. No compensatory effect by other transporters reportedly involved in fructose uptake in the liver and kidney were indicated at the mRNA level. These surprising findings indicated a previously unrecognized link through SGLT5 between renal fructose reabsorption and hepatic lipid metabolism.     

The Effects of Probenecid and Thiazides and Their Combination on the Urinary Excretion of Electrolytes and on Acid-base Equilibrium

The effects of commonly used therapeutic doses of hydrochlorothiazide and probenecid, given singly and in combination, on the urinary excretion of monovalent and divalent ions and on acid-base equilibrium were studied in four patients with idiopathic hypercalciuria.Probenecid had no effect on the urinary excretion of monovalent ions but resulted in a sustained increase in the urinary excretion of calcium, magnesium and citrate and a temporary increase in the urinary excretion of ammonium, in addition to its well-known effects on uric acid metabolism. A temporary fall in serum phosphorus levels was also observed.Probenecid also modified the response to hydrochlorothiazide in that the urinary excretion of calcium, magnesium and citrate was greater during combined therapy than when hydrochlorothiazide was administered alone. Probenecid prevented or abolished the increase in serum uric acid levels associated with the use of thiazide but did not modify the effects of hydrochlorothiazide on the urinary excretion of sodium, chloride, potassiu, phosphorus, ammonium, titratable acid and bicarbonate.     

Uric acid and urea in human sweat

The present study investigated whether thermal sweating may relieve elevated concentrations of serum uric acid or urea. Concentrations of uric acid and urea were measured in the sweat of sixteen male volunteers, who were treated with external heat after one hour of intense physical exercise. The same analytes were also measured in their urine and serum samples. Furthermore, creatinine and some electrolytes were determined in these specimens. The results show that the concentration of uric acid in the sweat is 24.5 micromol/L, which is only 6.3% of that in serum. The concentration of urea in the sweat is 22.2 mmol/L, which is 3.6 times that in serum. The results indicate that sweat uric acid concentration is quite minimal, and the estimated total uric acid excretion per day in normal physiological range is insignificant. However, the level of sweat urea was found at a much higher concentration than the serum level. No correlation could be established between the level of uric acid in sweat and in serum. There was also no correlation between the level of urea in sweat and that in serum. These results suggest it would not be effective to relieve the elevated serum uric acid concentration by thermal sweating when the renal excretion of uric acid is partly compromised. Nevertheless, the potential of urea excretion via profuse sweating is apparent particularly when the kidneys are damaged or their function is impaired. These findings also suggest that persons who take vigorous exercise or are exposed to hot environments should be well advised to drink adequate fluids since heavy sweating excretes only minimal uric acid, accompanied by significant diminution of urinary output and diminished urinary excretions of uric acid, which may induce elevated levels of serum uric acid.     

Effect of insulin on excretion and retention of infused glutamine amide-N in chickens (Gallus domesticus)

1. The purpose of this study was to examine the effects of insulin on urinary excretion and retention of the intravenously infused glutamine amide-15N in chickens. 2. Insulin pretreatment reduced urinary total 15N excretion (P less than 0.05) and enhanced 15N retention in chicken body (P less than 0.05), but it did not affect non protein-15N retained in the liver and blood. 3. Insulin decreased the incorporation of the infused glutamine amide-15N into urinary uric acid as well as the excretion of other N-derived urinary uric acid (P less than 0.05), which resulted in a significant decrease in total urinary uric acid (P less than 0.05). 4. There was no effect of insulin on urinary appearance of the infused glutamine amide-15N in the form of ammonia.     

Purine loss after repeated sprint bouts in humans.

The influence of the number of sprint bouts on purine loss was examined in nine men (age 24.8 +/- 1.6 yr, weight 76 +/- 3.9 kg, peak O(2) consumption 3.87 +/- 0.16 l/min) who performed either one (B1), four (B4), or eight (B8) 10-s sprints on a cycle ergometer, 1 wk apart, in a randomized order. Forearm venous plasma inosine, hypoxanthine (Hx), and uric acid concentrations were measured at rest and during 120 min of recovery. Urinary inosine, Hx, and uric acid excretion were also measured before and 24 h after exercise. During the first 120 min of recovery, plasma inosine and Hx concentrations, and urinary Hx excretion rate, were progressively higher (P < 0.05) with an increasing number of sprint bouts. Plasma uric acid concentration was higher (P < 0.05) in B8 compared with B1 and B4 after 45, 60, and 120 min of recovery. Total urinary excretion of purines (inosine + Hx + uric acid) was higher (P < 0. 05) at 2 h of recovery after B8 (537 +/- 59 micromol) compared with the other trials (B1: 270 +/- 76; B4: 327 +/- 59 micromol). These results indicate that the loss of purine from the body was enhanced by increasing the number of intermittent 10-s sprint bouts.