Urine Excretion In Rats Research Articles

Diuretic Activities of Root Bark Aqueous and Ethanolic Extracts of Parquetina nigrescens: I-Effects on Urinary Excretion in Wistar Rat

Background and objective: The root bark of Parquetina nigrescens is used in traditional medicine in the treatment of hypertension and edema for its diuretic properties. This study was conducted to examine the effects of this medicinal plant on the excreted urinary volume and contribute to scientific knowledge on its diuretic action. Methods: Water-overloaded rats were treated separately with increasing doses (5-70 mg/kg) of Parquetina nigrescens root bark aqueous and ethanolic 70 % extracts of and furosemide (FURO) at 5 mg/kg. Excreted urine was collected and measured. Results: Plant extracts caused increased urine excretion in rats. PNea 15 mg/kg and PNee 25 mg/kg were the most active doses. They caused an increase of volume of urine comparable to that induced by FURO 5 mg/kg. A very significant elimination of water overload at p < 0.001 was observed. And the recorded values were 42.73 ± 0.26% (PNea 15 mg/kg), 45.39 ± 0.190% (PNee 25 mg/kg) and 73.6 ± 0.24% (FURO 5 mg/kg) against 29.73 ± 0.24% (Saline solution NaCl 0.9%). Conclusion and perspectives: Increase of urine volume excreted induced by the extracts partly confirms the diuretic virtue of Parquetina nigrescens justifying its empirical use to treat hypertension and edema. However, these results, on their own, do not make it possible to elucidate the mechanism underlying diuretic activity of this plant. Additional studies should be carried out for this purpose.
 Keywords: Diuretic activity, urinary excretion volume, Parquetina nigrescens, Furosemide

The effect of saponins from Ampelozizyphus amazonicus Ducke on the renal Na+ pumps’ activities and urinary excretion of natriuretic peptides

BackgroundIn a previous study, we showed that a saponin mixture isolated from the roots of Ampelozizyphus amazonicus Ducke (SAPAaD) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAPAaD- induced antidiuresis in rats.MethodsTo evaluate the effect of SAPAaD on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAPAaD (SAPAaD + Furo) or 0.5 ml of 0.9 % NaCl (NaCl + Furo). In the SAPAaD + NaCl group, rats were pretreated with SAPAaD and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na+ pumps on antidiuretic effects promoted by SAPAaD, rats were given the physiological solution (as above) containing SAPAaD (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na+- and (Na+,K+)-ATPases were calculated from the difference between the [32P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively.ResultsIt was observed that SAPAaD inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, NaCl + Furo group, n = 5, to 5.9 ± 1.0 mL, SAPAaD + Furo group n = 5, p < 0.05), increased both Na+-ATPase (from 25.0 ± 5.9 nmol Pi.mg-1.min-1, control, to 52.7 ± 8.9 nmol Pi.mg-1.min-1, p < 0.05) and (Na+,K+)-ATPase (from 47.8 ± 13.3 nmol Pi.mg-1.min-1, control, to 79.8 ± 6.9 nmol Pi .mg-1.min-1, p < 0.05) activities in the renal cortex. SAPAaD also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP.ConclusionWe concluded that the SAPAaD antidiuretic effect may be due to an increase in the renal activities of Na+- and (Na+,K+)-ATPases and/or a decrease in the renal ANP.

General pharmacological properties of YJA20379-8, a new H+/K(+)-ATPase inhibitor with anti-ulcer activities.

The general pharmacological properties of YJA20379-8 (3-butyryl-4-[(R)-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, CAS 187654-40-6), a new H+/K(+)-ATPase inhibitor with anti-ulcer activities, were investigated in mice, rats and guinea pigs. YJA20379-8 at oral doses of 25, 50 and 100 mg/kg did not affect the locomotor activity, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic action and anticonvulsant action at the doses of 100 mg/kg p.o. The respiration and blood pressure were not affected at 10 mg/kg i.v. in rats. YJA20379-8 at 2 x 10(-4) g/ml did neither produce any contraction nor relaxation of isolated organs, such as guinea pig ileum, rat fundus, rat uterus and guinea pig vas deferens, and the drug antagonized the contractile responses to several spasmogens, such as acetylcholine, histamine, serotonin, L-phenylephrine, oxytocin and BaCl2. The drug up to 100 mg/kg p.o. did not affect pupil size and the intestinal propulsion of mice. And it did not show an anticarrageenan action at 100 mg/kg. In this general pharmacology study, hypothermic effect in mice, retardation in gastric emptying in rats, decreases in urine excretion in rats at oral doses of 50 and 100 mg/kg of YJA20379-8 and the spasmolytic activity could be found. However, no other effects were exhibited at a high oral dose of 100 mg/kg in animals in this study.

Aclidinium bromide, a novel long-acting muscarinic antagonist for COPD with improved preclinical renal and urinary safety profile

AimsAclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist currently in registration phase for the treatment of chronic obstructive pulmonary disease. Since urinary difficulty and retention have been reported for anticholinergic agents such as tiotropium and ipratropium, it is important to examine the preclinical urinary and renal safety profile of aclidinium. Main methodsThe effect of aclidinium on urine and electrolyte excretion, renal function and voiding cystometry was analysed in conscious water-loaded Wistar rats (10–1000μg/kg, s.c.), anaesthetised Beagle dogs (1000μg/kg, i.v.) and anaesthetised guinea pigs (3–100μg/kg, intratracheally), respectively. Aclidinium plasma levels were determined in an independent study. Active comparators were tiotropium (all studies) and ipratropium (cystometry only). Key findingsAclidinium 1000μg/kg had no effect on urine excretion in rats, in contrast to tiotropium 100μg/kg which significantly decreased this parameter (p<0.05). Aclidinium 1000μg/kg also had no effect on renal function in Beagle dogs. In guinea pigs, aclidinium 3–100μg/kg had no effect on urinary bladder function, whereas tiotropium and ipratropium 100μg/kg decreased the peak micturition pressure (p<0.05), increased the volume of urine retained in the bladder (p<0.01) and showed a trend to decrease the volume of urine excreted. SignificanceAclidinium had no significant effect on urinary and renal function in the animal models studied. These results, together with the rapid plasma clearance of aclidinium reported previously, suggest a lower propensity to induce urinary retention in humans than tiotropium and ipratropium.

Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume. Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration. Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed. Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Zolpidem increases bladder capacity and decreases urine excretion in rats

To clarify the effects of zolpidem, a gamma-aminobutyric acid (GABA)(A) receptor agonist, on bladder function, and urine production, we investigated the effects of zolpidem administration on bladder overactivity induced by cerebral infarction (CI) and on urine excretion increased by water overloading in Wistar rats. CI was induced by left middle cerebral artery occlusion. The effects on bladder function of zolpidem alone or in combination with the GABA(A) receptor antagonist bicuculline, were then examined in the CI rats using cystometry. The antidiuretic effect of zolpidem was investigated in water-loaded and Brattleboro rats (genetically vasopressin-deficient). Blood samples were collected from water-loaded rats to determine the aldosterone level 1 and 6 hr after zolpidem administration. Zolpidem increased bladder capacity dose-dependently, but had no significant effect on bladder contraction pressure in CI rats. Bicuculline dose-dependently inhibited zolpidem-induced increases in bladder capacity without affecting bladder contraction pressure. Zolpidem dose-dependently decreased the volume of urine excreted in water-loaded and Brattleboro rats. Compared with the control group, zolpidem significantly increased the aldosterone concentration in the plasma of water-loaded rats 1 hr after administration. Zolpidem increased bladder capacity via a GABAergic mechanism in CI rats, and suppressed urine excretion via a pathway that was not through activation of vasopressin V(2) receptors in water-loaded and Brattleboro rats. These results suggest that zolpidem may improve nocturia via an increase in bladder capacity and a decrease in urine excretion.

Formate excretion in urine of rats fed dimethylaminoazobenzene-rich diets: the possibility of formate formation from D-lactate.

This experiment was carried out to evaluate the possibility of degradation of d-lactate into formate and acetaldehyde. In order to induce hyperproduction of d-lactate in rats. Donryu male albino rats were fed diets containing 0.064% 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB), 4'-methyl-4-dimethylaminoazobenzene (4'-MDAB) or 2-methyl-4-dimethylaminoazobenzene (2-MDAB) for 10 weeks. During the experiment, body mass, food and water intake and volume of urine were documented. Methylglyoxal, D-lactate and formate in the urine samples were determined. On the first day of the eleventh week, methylglyoxal, D-lactate, glutathione and enzymatic activities of demethylation and glyoxalase I and II in liver were measured. Methylglyoxal, D-lactate and clinical chemistry parameters of blood plasma were also measured. The levels of methylglyoxal and D-lactate in livers of rats fed 3'-MDAB were very high, while those of 2-MDAB fed-rats and the control group were the same. The fact that glyoxalase I activity and the level of glutathione, a cofactor of glyoxalase I, were high in the livers of the 3'-MDAB-fed rats can explain the elevated levels of methylglyoxal and D-lactate in the liver. The most striking results were the elevated formate levels in the urine of rats fed 3'- and 4'-MDAB in a precancerous state. The degradation of D-lactate, an end product of the methylglyoxal bypass, into acetaldehyde and formate was suggested as a possible way to explain the results.

Gas chromatography–mass spectrometry profile of urinary organic acids of Wistar rats orally treated with ozonized unsaturated triglycerides and ozonized sunflower oil

The main products in the ozonolysis of unsaturated triglycerides or vegetable oils are peroxides, aldehydes, Criegee ozonides and carboxylic acids. Some of these compounds are present in different concentrations in the biological fluids. The aim of this work is to study, using gas chromatography–mass spectrometry (GC–MS), the organic acid excretion in urine of rats orally treated with ozonized sunflower oil (OSO), ozonized triolein or ozonized trilinolein. Oral administration of OSO to Wistar rats has produced changes in the urinary content of dicarboxylic organic acids. Among others heptanedioic (pimelic acid) and nonanedioic acids (azelaic acid) were the major increased dicarboxylic acids found. The urinary dicarboxylic acid profiles of rats which received ozonized triolein only showed an increase in heptanedioic and nonanedioic acids. However, when ozonized trilinolein is applied, the profile is similar to that obtained when OSO is administered. A biochemical mechanism is proposed to explain the formation of dicarboxylic acids from ozonated unsaturated triglycerides.

Strain difference in free p-cresol excretion in urine of rats exposed to toluene at sub-narcotic concentrations.

Since the observation on strain difference in toluene metabolism in rats, evidence has been accumulating in this laboratory to suggest that possibly there is an ethnic-related difference in organic solvent metabolism in humans. A significant difference in o-cresol/hippuric acid ratio after exposure to toluene was first observed among the four strains of rats, and its presence was further confirmed also in workers of various ethnic backgrounds. In this report, analyses were made for additional evidence on strain difference in animals to consolidate the observation in workers, and it was found that free p-cresol excretion varied in rats of various strains exposed to toluene. The observation on total p-cresol which has been previously reported, will be discussed also in this report.

The metabolism and kinetics of 125I-labeled human intravenous IgG preparation (C-425) in rats and rabbits. I. Blood clearance, excretion into urine and feces, and brain uptake.

The metabolism of intravenous human IgG preparation (C-425) was studied by the use of 125I-C-425 in rats and rabbits after intravenous injection of the compound particularly with regard to changes in the levels of radioactive compound or metabolites in the blood as a function of time as well as levels excreted in urine and feces. Brain uptake index of 125I-C-425 was estimated by a slightly modified Oldendorf's method. 125I-Polyglobin was used as the control compound. The half-life of blood clearance of 125I-C-425 radioactivity after the 2nd day was about 8 days in rats and about 5 days in rabbits, respectively. Within a relatively short period of 1 hour, a rapid decrease of blood concentration of radioactivity was recorded. This was due to the transfer of labelled compound from blood into the extravascular compartment. A high concentration of radioactivity in the blood was maintained for one week after intravenous injection of the labelled compound in both rats and in rabbits. Most of the radioactive compound or metabolites were excreted in the urine and relatively little in feces. Excretion in urine of rats reached about 22% for 125I-C-425 and about 17% for 125I-Polyglobin. The excretion rate slowed down over 24 hours. The total recovery rates in rats were about 40% for 125I-C-425 and 125I-Polyglobin and about 55% in rabbits for both drugs. The permeability through the blood-brain barrier was found to be negligible for both drugs.

Effect of Dietary Protein Levels on the Plasma Amino Acid Ratio and Hydroxyproline Excretion in Urine of Rats

The relationship between the plasma amino acid ratio recommended by Whitehead and the weight gain or protein level in the diet was studied using male rats weighing about 90g. The animals were given diets containing graded amounts of casein for 9-41 days. The amino acid ratio, estimated by a modification of Whitehead's method, was found to be closely correlated with the weight gain and also the dietary protein level.When the animals were given either a rice or wheat flour diet supplemented with lysine and threonine, a close relationship between the amino acid ratio and weight gain was also observed.In our animal experiments, the hydroxyproline index which could be related to the incidence of the clinical signs of Kwashiorkor was also found to correlate well with the amino acid ratio and weight gain.

Influence of the Protein Content in the Diet on Urocanic Acid Excretion in Urine of Rats

Male Wistar rats (80-130g) were fed diets containing 0, 5, 25 or 60% casein. Experimental diets were consumed during a 2-week dietary adjustment period followed by a 2-week metabolic-period. During the metabolic period the rats were given L-histidine solution dosed orally, and samples of urine were collected at 4 day-intervals.By increasing the amount of histidine dosed, excretion of free histidine and urocanic acid in urine was increased in rats fed any diet. Ratios of urocanic acid to histidine and urocanic acid to creatinine were higher in the non-protein group than that of the other groups, while these ratios were not so different among the groups of rats fed 5, 25 or 60% casein diets.

Early effects of carbon tetrachloride on ascorbic acid concentration in liver and ascorbic acid excretion in urine of rats

Die Wirkung von CCl4 auf die Ascorbinsaure-Konzentration in der Leber und die Ascorbinsaure-Ausscheidung mit dem Harn wurde bei erwachsenen Ratten innerhalb der ersten 22 Std nach der Applikation untersucht. In der Fruhphase der CCl4-Wirkung kommt es zum Anstieg der Konzentration in der Leber. Der fruheste signifikante Anstieg wurde 30 min nach der Applikation beobachtet. Das Maximum wurde dosisabhangig zwischen 90 und 180 min erreicht.

Dose Dependency of Radiation-Induced Creatine Excretion in Rat Urine

Creatine excretion in urine of rats after whole-body exposure to various doses of x rays (25 to 1000 r) and after sham-irradiation was determined. Although creatinuria was observed at all levels of exposure, the degree was dependent on the dose. Creatinuria lasted from 3 to 16 days after exposure. In the intermediate dose range a second rise in the excretion of creatine was observed during the second week after exposure. The average creatine excretion during the initial 4 days after exposure varied linearly with the dose up to 650 r.