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PubMed1993

Effect of water immersion on renal natriuretic peptide (urodilatin) excretion in humans.

We examined 1) the effect of thermoneutral (34.5 +/- 0.5 degrees C) water immersion to the neck (WI) in humans on the temporal profile of renal urodilatin [atrial natriuretic peptide- (ANP) (95-126)] excretion and 2) the relationship between urodilatin and urinary fluid (V) and sodium (UNaV) excretion. Eight normal subjects underwent 12 h of WI, and another group of eight were studied during seated control conditions. The subjects ingested 200 ml of tap water hourly. WI induced an increase in renal urodilatin and guanosine 3',5'-cyclic monophosphate (cGMP) excretion, V, and UNaV. After peak values were attained between the 2nd and 5th h of WI, urodilatin and cGMP excretion, V, and UNaV returned toward preimmersion and control levels. At the 12th h of WI, urodilatin and cGMP excretion and V were indistinguishable from preimmersion values but were significantly elevated compared with the control values. UNaV was maintained elevated compared with both preimmersion and control values. During WI, positive and statistically significant linear correlations could be established between V and renal urodilatin excretion in six subjects and between UNaV and urodilatin excretion in four subjects. We conclude that WI induces an increase in the rate of renal urodilatin excretion, attaining a peak value at the 3rd h followed by an attenuation toward preimmersion and control levels. Furthermore, urodilatin might participate as one of several mechanisms of the natriuresis and diuresis of WI in humans.

Adult↗
PubMed2000

Effect of dietary intake on urinary oxalate excretion in calcium oxalate stone formers in their forties.

PURPOSE: To examine the influence of dietary intake on urinary oxalate excretion in calcium oxalate stone formers in their forties. PATIENTS AND METHODS: Dietary intake was recorded by using the dietary-record method in 58 idiopathic stone formers in their forties. The patients collected their urine for 24 h at home and their urinary oxalate excretion was measured. The relationship between the dietary intake of various nutrients and urinary oxalate excretion was examined by mono- and multivariate analysis. RESULTS: The intake of animal fat was correlated with urinary oxalate excretion by monovariate analysis, but that of total protein, animal protein, calcium and carbohydrate were not. By multivariate analysis, the intake of animal fat was correlated with urinary oxalate excretion and the intake of calcium was inversely correlated with urinary oxalate excretion. CONCLUSION: The intake of animal fat was positively and the intake of calcium was negatively correlated with the urinary oxalate excretion in stone formers in their forties. It was shown that animal fat plays an important role in urinary oxalate excretion.

Adult↗
PubMed2003

Increased urinary protein excretion in children from families with balkan endemic nephropathy.

BACKGROUND: Balkan endemic nephropathy (BEN) has not been described in children, however some previous studies of children from families with BEN have revealed abnormalities of the urinary tract including an increased urinary protein excretion. METHODS: In the present study, urinary excretion of total protein was studied in 703 healthy children, aged 9-13, from endemic and non-endemic settlements around the South Morava River. Since BEN is an environmentally induced disease, with possible seasonal variation of toxin(s), children were studied three times a year: in spring, autumn and winter, during a 3-year period. After a water load of 15 ml/kg body weight, a 3-hour urine sample was collected, from 7 to 10 a.m. RESULTS: Protein excretion in urine was highest in children from families with BEN compared with the excretion in children from the city, non-endemic villages, and those from non-endemic families living in the same settlements. This was the case during all three periods investigated in the second year of the study. In the autumn term of all three years of the study, protein excretion was significantly higher in children from families with BEN than in children from the city and from non- endemic families living in the same settlements. If the upper limit of protein excretion is set at 34 mg/mmol creatinine, then increased protein excretion in autumn was found in the first year of study in 9/229 children from endemic settlements and in only 4/474 children from non-endemic areas (p = 0.004); in the second year in 5/229 and 3/474 children (p = 0.069), and in the third year in 10/229 and 4/474 children (p = 0.002), respectively. CONCLUSIONS: We have presented evidence that children from families with BEN and endemic villages consistently excreted significantly more protein in the autumn, and in three seasons (spring, autumn, winter) in 1 year of our study. These results are consistent with seasonal variations in exposure to an environmental toxin(s).

Adolescent↗
PubMedDate not supplied

Effects of ibuprofen and indomethacin on urinary antidiuretic hormone excretion in preterm infants treated for patent ductus arteriosus.

OBJECTIVE: To compare the effects of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on urinary antidiuretic hormone (ADH) excretion, as a cause of oliguria. STUDY DESIGN: Forty-four respiratory distress syndrome prematures (<or=34 weeks' gestation) with PDA received either ibuprofen (n = 22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or three doses at 12-hour intervals of indomethacin (n = 24), 0.2 mg/kg, both infused continuously over a period of 15 min. Urinary ADH excretion, diuresis, serum creatinine, urinary sodium, fractional excretion of sodium, and urinary osmolality were measured before and after treatment. RESULTS: Indomethacin treatment caused a significant decrease in urinary ADH excretion (21.8 +/- 20.8 vs. 13.8 +/- 12.9 pg/ml; p < 0.05), along with a significant reduction in urinary sodium (92.1 +/- 36.1 vs. 64.8 +/- 35.6; p < 0.05), fractional excretion of sodium (68.5 +/- 37.1 vs. 45.6 +/- 37.1; p < 0.05), and urinary osmolality (276.2 +/- 103.9 vs. 226.4 +/- 60.3; p < 0.05). Ibuprofen treatment did not modify urinary ADH excretion and caused a statistically insignificant decrease in urinary sodium and in fractional excretion of sodium. CONCLUSIONS: Compared with ibuprofen, indomethacin caused a significant reduction in urinary ADH excretion and a significant decrease in urinary sodium and osmolality.

Cyclooxygenase Inhibitors↗
PubMed2005

Role of chronic inhibition of dopamine-metabolizing enzymes in the regulation of renal sodium and phosphate excretion in the rat remnant kidney.

BACKGROUND/AIMS: The present study examined the effects of chronic selective or combined inhibition of type A monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) on daily urinary excretion of dopamine and metabolites and on natriuresis and phosphaturia in 3/4 nephrectomized (3/4nx) and Sham rats. METHODS: The 3/4nx and Sham rats were placed in metabolic cages and received the MAO-A-selective inhibitor Ro-411049 (7.5 mg x kg(-1) bid) and/or the COMT-selective inhibitor BIA 3-202 (30 mg x kg(-1) bid) orally for 3 days during high sodium diet. RESULTS: Selective COMT inhibition increased the urinary excretion of the deaminated metabolite (3,4-dihydroxyphenylacetic acid, DOPAC) and decreased the urinary excretion of the methylated (3-methoxytyramine, 3-MT) and deaminated plus methylated metabolite (homovanillic acid, HVA) in both groups. Selective MAO-A inhibition increased the urinary excretion of 3-MT and reduced the urinary excretion of both DOPAC and HVA in either 3/4nx or Sham rats. Combined inhibition of MAO-A and COMT did not significantly change the urinary excretion of DOPAC and markedly decreased the urinary excretion of 3-MT and HVA in both groups. Selective or combined inhibition of MAO-A and COMT did not alter the daily urinary excretion of dopamine, sodium or phosphate in either 3/4nx or Sham rats. CONCLUSIONS: Chronic selective or combined inhibition of MAO-A and COMT is not of major importance in regulating the dopamine-dependent natriuresis and phosphaturia in either 3/4nx or Sham rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Effects of organic anions on biliary glutathione excretion in rats.

The effects of various organic anions (2 mumol/100 g body weight) on biliary glutathione excretion were studied in rats. Bromosulfophthalein markedly inhibited glutathione excretion, whereas dibromosulfophthalein was a less potent inhibitor. Experiments with different bromosulfophthalein doses revealed that the extent of inhibition of glutathione excretion was related to the total bromosulfophthalein excretion. Indocyanine green also inhibited biliary glutathione excretion. Dinitrophenyl glutathione and pravastatin did not inhibit biliary glutathione excretion. These findings indicate the existence of several pathways of biliary excretion of organic anions and suggest that one of them is a pathway for biliary glutathione excretion.

Animals↗
PubMed1987

Effect of high-dose aldosterone infusions on renal electrolyte excretion in patients with renal insufficiency.

We investigated the effect of aldosterone infusion (0.5 mg/h for 6 h) on electrolyte excretion in 11 patients with severe renal insufficiency (creatinine clearance 6-20 ml/min), with normal or elevated serum potassium levels and a wide range of plasma aldosterone levels, and compared the data with those obtained in 7 healthy subjects. The studies were done under conditions of fixed sodium and potassium intake. In the normal subjects, aldosterone infusion caused a significant rise in potassium excretion and a significant fall in sodium and chloride excretion (p less than 0.01). In 1 patient with a high plasma aldosterone, virtually no response occurred to the aldosterone infusion. In the others, the increase in potassium excretion and reduction in chloride excretion were not different from the changes observed in the normals, but the fall in sodium excretion was less due to a higher urinary sodium before infusion in the normals (p less than 0.05). Fractional electrolyte excretions as well as the changes in fractional excretion by aldosterone were larger in the patients (p less than 0.05). Apparently, the renal tubules of patients with chronic renal failure are still responsive to maximal stimulation with aldosterone, in spite of their basically elevated fractional electrolyte output. These findings suggest that, with some exceptions, the hyperkalemia in patients with chronic renal failure is in part due to relative hypoaldosteronism.

Adult↗
PubMed1991

Urinary albumin excretion in normal pregnancy and pregnancy-induced hypertension.

We measured the urinary excretion of albumin in 67 healthy primigravidae, at monthly intervals, from 16 to 36 weeks of gestation and 12 weeks postpartum. Of the 67 primigravidae, 55 completed a normal pregnancy and 12 developed pregnancy-induced hypertension. In the latter group, an additional measurement of urinary albumin excretion was performed at 24 weeks postpartum. The aims of the study were: to look for changes of urinary albumin excretion during the progression of normal pregnancy; to assess if microalbuminuria could be an early feature of pregnancy-induced hypertension; to evaluate the effects of physical activity on the excretion of albumin in normal pregnancy and pregnancy-induced hypertension. In contrast with glomerular hyperfiltration and increased urinary total protein, two recognized characteristics of the pregnant state, we found that normal primigravidae, during the day, excrete significantly less albumin (p between less than 0.01 and less than 0.001) in comparison with the postpartum period and nonpregnant women. Normal primigravidae, as a group, showed parallel changes of urinary albumin excretion and diastolic blood pressure throughout pregnancy and postpartum, suggesting an important physiologic role of hemodynamic factors in regulating glomerular permeability to albumin. The daytime urinary albumin excretion in patients developing pregnancy-induced hypertension was significantly higher (p between less than 0.005 and less than 0.001) than in normal pregnancy from the 28th gestational week onwards. The increased urinary albumin excretion preceded the onset of hypertension and tended to persist long after blood pressure had returned to normal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1996

Urinary excretion of Tamm-Horsfall protein in normotensive, normo-albuminuric type 1 diabetic patients.

The excretion rate of a marker of distal tubular function, Tamm-Horsfall protein (THP), has been measured in urine (micrograms/min) overnight, during orthostasis and during a glycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 41 normotensive, normo-albuminuric type 1 diabetic patients. Eleven healthy subjects who were not clamped served as controls. A further 4 normo-albuminuric type 1 diabetic patients were rendered euglycaemic without a waterload. The excretion rate of THP overnight was similar in type 1 diabetic patients and normal subjects (26.1 vs. 23.5 micrograms/ml, p = NS). During the waterloaded euglycaemic clamp, THP increased significantly both in type 1 diabetic patients and control subjects (p < 0.001), but the increase was slightly greater in type 1 diabetic patients (67.2 vs. 38.4 micrograms/min, p = 0.05). Orthostasis did not increase the excretion rate of THP in either type 1 diabetic patients or in control subjects. In the 4 type 1 diabetic patients who were only clamped, the THP excretion rate increased less compared to the clamp plus waterload experiment (means: overnight 11.3 micrograms/min; clamp 22.5 micrograms/min). In Type 1 diabetes, overnight THP excretion was inversely correlated both with fasting blood glucose, HbA1 and sodium-lithium counter-transport activity (SLC). A direct relationship was present between urinary flow and the excretion rate of THP. In conclusion, this study shows that normotensive, normo-albuminuric type 1 diabetic patients present similar overnight excretion rates of THP compared to healthy controls and that the excretion rate of THP is unaffected by posture and increased during acute euglycaemia and waterload. The association between SLC and THP might suggest some relation between this putative marker of nephropathy and distal tubular function, but this finding needs confirmation and further study.

Adjuvants, Immunologic↗
PubMed1997

Evaluation of urinary glycosaminoglycan excretion in patients with renal cell carcinoma.

OBJECTIVE: To evaluate a possible correlation between the urinary excretion of glycosaminoglycans (GAGs) and tumor stage and size in renal cell cancer (RCC), a prospective controlled study was performed. METHODS: 34 patients (13 females, 21 males) with clinically and histologically proven RCC were included in the study. Following the staging procedures of RCC in each patient nephrectomy was performed; subsequently the size of the tumor (length and width) was calculated using nephrectomy material. Urinary GAG excretion was determined using a previously described method. RESULTS: Urinary GAG excretion was found to be increased in RCC patients, with a strong relation to the size of the tumor. Patients with relatively larger tumor masses seemed to excrete higher amounts of GAGs in urine (r = 0.8235; p < 0.001). In contrast, we were not able to show any significant difference in urinary GAG excretion with respect to tumor stage (f = 5.92; p = 0.0068). Patients with multiple foci of RCC (n = 3) had relatively higher rates of GAG excretion than patients with same-size single-tumor masses. CONCLUSIONS: Although our results revealed GAG excretion in RCC patients as a possibly useful marker with respect to tumor size, no correlation to the stage of RCC was observed. Further investigation using larger series of patients and other definitive parameters is certainly needed in order to provide more reliable data, before considering urinary GAG excretion as a useful marker.

Biomarkers, Tumor↗
PubMed1987

Do hypertensive patients have a different diurnal pattern of electrolyte excretion?

Studies generally indicate that excretion of sodium, potassium, and water is greater during the day than during the night. To determine whether hypertensive patients exhibit this same pattern of excretion, diurnal variations in excretion of sodium, potassium, creatinine, and water were examined in 107 hypertensive men and women from a clinical trial on control of hypertension by nonpharmacological means--the Hypertension Control Program. Each participant provided two carefully timed 24-hour urine collections divided into daytime and overnight specimens. The median ratios of 24-hour to 8-hour overnight excretion were 2.84, 3.95, 2.99, and 2.77 for sodium, potassium, creatinine, and water, respectively. Thus, more than half of this hypertensive group exhibited a greater rate of sodium and water excretion during sleep than during daytime hours, a reversal of the usual pattern. When the group was subdivided based on age, sex, race, trial randomization group, use of diuretics, and hypertension severity, women had significantly lower ratios of 24-hour to overnight excretion for sodium and water than men and blacks had significantly lower 24-hour to overnight ratios for water and potassium than whites. When the 24-hour to overnight ratios for these hypertensive patients were compared with those for a group of 30 men and women with high-normal blood pressure, those with high-normal blood pressure had significantly larger ratios for sodium and water excretion than the hypertensive group. The results of this study suggest that hypertensive patients may have a different diurnal pattern of sodium and water excretion than normotensive subjects and that further research is needed to clarify this issue.

Adult↗
PubMed1993

Renal sodium excretion in sons of hypertensive parents.

The objective of this study was to evaluate whether renal excretion of sodium is impaired and whether tubular reabsorption of sodium is increased in normotensive white men with a familial predisposition to develop essential hypertension. We compared 11 normotensive sons of two hypertensive parents (SOHT) with 11 normotensive sons of two normotensive parents (SONT); renal sodium handling was assessed after 1 week of low-sodium diet (10 mmol/d) and after 1 week of high-sodium diet (200 mmol/d). The SOHT were on average 5.5 years older than the SONT (46.9 +/- 5.2 [SD] vs 41.4 +/- 4.1, P = .012). On the sixth day of each diet, mean urinary sodium excretion did not differ between the two groups (12.9 +/- 6.3 vs 12.7 +/- 6.7 mmol/d on low-sodium diet, P = .930; 197 +/- 25 vs 200 +/- 27 mmol/d on high-sodium diet, P = .817). On the seventh day of each diet, baseline means for filtered load of sodium, absolute excretion of sodium, fractional excretion of sodium (an index of total tubular sodium reabsorption), and fractional excretion of lithium (an inverse index of proximal tubular sodium reabsorption) also did not differ between the groups. To assess renal sodium handling under non-steady-state conditions, we infused 2 L normal saline intravenously over a 2-hour period. The means for absolute excretion of sodium, fractional excretion of sodium, and fractional excretion of lithium increased from baseline, but the increases did not differ in magnitude between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Altered urinary excretion of elastin cross-links in premature infants who develop bronchopulmonary dysplasia.

In order to determine whether elastin degradation is increased in infants whose respiratory insufficiency requires ventilation with high concentrations of O2, we quantitated, by amino acid analysis, the elastin degradation products (desmosines) excreted in the urine of 14 premature male infants during the first 3 wk of life. Eight of these infants, the "low-O2" infants, did not have severe lung disease and did not require more than 40% O2 beyond the first 8 h of life. The other 6 infants, selected retrospectively because they developed bronchopulmonary dysplasia (BPD), were ventilated with more than 60% O2 for at least the first 72 h of life. The pattern of desmosine excretion observed in infants who developed BPD differed significantly (p less than 0.05) from the excretion pattern seen in "low-O2" infants during the first 3 wk of life. At the end of the first week of life, desmosine excretion was significantly greater (p less than 0.05) in the infants who later developed BPD than in the "low-O2" infants without severe lung disease. From Days 7-9 to 20-22, desmosine excretion increased in the "low-O2" infants from 6.9 +/- 1.7 micrograms/kg to 9.0 +/- 3.5 micrograms/kg. In contrast, desmosine excretion did not remain elevated in the BPD infants, decreasing from 10.6 +/- 2.2 micrograms/kg to 6.1 +/- 2.9 micrograms/kg during the same period. In the BPD infants, elevated desmosine excretion through Day 9 is likely to reflect lung injury, whereas decreased desmosine excretion beyond Day 9 suggests that elastin synthesis and turnover is impaired, possibly as a result of nutritional deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1968

Renal excretion of urobilinogen in the dog.

The renal excretion of urobilinogen was studied in dogs by standard clearance techniques. The use of radiochemically pure tritiated mesobilirubinogen as a representative urobilinogen afforded much greater analytical precision than can be obtained with the usual colorimetric and fluorimetric techniques which are only semiquantitative. With constant plasma levels of urobilinogen, raising urinary pH from 5 to 8 increased urobilinogen excretion from about 30% to up to 200% of the filtered load. When urinary pH was kept constant, changes in blood pH had no effect on urobilinogen excretion. Increases in urinary flow had no effect on urobilinogen excretion when the urine was alkaline but increased excretion markedly during aciduria. Probenecid did not influence urobilinogen excretion by the kidney. It is concluded that urobilinogen is excreted by a three-component system of glomerular filtration, active secretion, and pH-dependent nonionic diffusion in the distal nephron. Urobilinogen is a weak acid, and this mode of excretion is similar to that of other weak, organic acids, such as salicylates. These results indicate that urinary pH and flow must be considered in the clinical interpretation of measurements of urinary urobilinogen.

Acidosis↗
PubMed1970

The effects of unsaturated dietary fats on absorption, excretion, synthesis, and distribution of cholesterol in man.

Cholesterol balance studies were carried out in 11 patients with various types of hyperlipoproteinemia to determine the mechanism by which unsaturated fats lower plasma cholesterol. Unsaturated fats produced no increase in fecal endogenous neutral steroids in 10 of 11 patients and no decrease in absorption of exogenous cholesterol in 5 patients who received cholesterol in the diet. In 8 of 11 patients no changes occurred in excretion of bile acids during the period on unsaturated fat when plasma cholesterol was declining. However, in 3 of 11 patients small but significant increases in bile acid excretion were found during this transitional period; in 2 others increases also occurred after plasma cholesterol had become constant at lower levels on unsaturated fat.Since the majority of patients showed no change in cholesterol or bile acid excretions during the transitional period, we propose that when excretion changes did occur they were probably not the cause of the plasma cholesterol change. Furthermore, turnover data and specific activity curves suggested that cholesterol synthesis was not influenced by exchange of dietary fats. Thus, excluding changes in excretion and synthesis, we conclude that it is most likely that unsaturated fats cause plasma cholesterol to be redistributed into tissue pools. We have also examined the possibility that cholesterol which is redistributed into tissues could be secondarily excreted as neutral steroids or bile acids. In at least 5 of 11 patients excretion patterns were consistent with this explanation. However, we cannot rule out that excretion changes may have been due to alterations in transit time, to changes in bacterial flora, or to transitory changes in absorption or synthesis of cholesterol or bile acids. Our conclusion that unsaturated fats cause a redistribution of cholesterol between plasma and tissue pools points to the necessity in future to explore where cholesterol is stored, to what extent stored cholesterol can be mobilized, and to define the factors governing these fluxes.

Adolescent↗
PubMed1982

Studies on the mechanism of sodium excretion during drug-induced vasodilatation in the dog.

The administration of vasodilating agents such as bradykinin and acetylcholine cause an increase in urinary sodium excretion. Yet the mechanisms involved in this natriuretic effect are not clear. Recent studies with another renal vasodilator, secretin have shown this drug also causes a profound increase in renal blood flow but without major changes in sodium excretion. To attempt to delineate the basis of this difference in sodium excretion with these drugs, the renal functional effects of secretin and bradykinin were compared at an equivalent vasodilating dose. Bradykinin increased renal blood flow from 222 to 342 ml/min, urine volume from 0.2 to 1.2 ml/min, and urine sodium excretion from 28 to 115 mueq/min. Urine osmolality fell from 1,230 to 401 mosmol/kg. Secretin caused a comparable increase in renal blood flow (216 to 325 ml/min) while changes in urine flow, sodium excretion, and urine osmolality were significantly less. In further studies papillary plasma flow was estimated using the albumin accumulation technique. Control papillary plasma flow was 29 ml/min per 100 g. Bradykinin increased urinary sodium excretion 108 mueq/min and decreased urinary osmolality from 1,254 to 516 mosmol/kg in association with a rise in papillary plasma flow to 62 ml/min per 100 g. Urine sodium excretion, urinary osmolality, and urine flow rate, as well as papillary plasma flow rate (32 ml/min per 100 g) were unchanged from control when secretin was administered. Studies with acetylcholine were qualitatively similar to those of bradykinin. Renal blood flow increased from 150 to 248 ml/min, urinary sodium excretion increased from 20 to 243 mueq/min, urinary osmolality decreased from 1,237 to 411 mosmol/kg and papillary plasma flow increased from 39 to 52 ml/min per 100 g. It is suggested that the natriuretic effect of some vasodilators is due, at least in part, to alterations in medullary hemodynamics, as evidenced by the increase in papillary plasma flow seen with bradykinin and acetylcholine, but not secretin.

Acetylcholine↗
PubMed1984

Biliary excretion of glutathione and glutathione disulfide in the rat. Regulation and response to oxidative stress.

Regulation of the biliary excretion of reduced glutathione (GSH) and glutathione disulfide (GSSG) and responses to selected model toxins were examined in male Sprague-Dawley rats. In control and phenobarbital-pretreated rats in which the intrahepatic concentration of GSH was modulated by the administration of diethyl maleate or acetaminophen, the biliary concentration of GSH was consistently lower than, but directly proportional to, the intrahepatic concentration of GSH. Furthermore, increments in bile flow produced by the infusion of sulfobromophthalein (BSP)-glutathione were associated with proportional increases in the biliary excretion of GSH, suggesting that GSH passes into bile passively along a concentration gradient. In contrast, GSSG appears to be secreted into bile against a steep concentration gradient. An increased hepatic production and biliary excretion of GSSG resulted from the administration of t-butyl hydroperoxide. Measurement of biliary GSSG and BSP during a constant infusion of the GSH adduct of BSP indicated that GSSG shares a common excretory mechanism with GSH adducts. Diquat, nitrofurantoin, and paraquat also markedly stimulated the biliary excretion of GSSG. On a molar basis, these compounds generated much more GSSG than a direct substrate for glutathione peroxidase such as t-butyl hydroperoxide, indicating that the compounds undergo redox-cycling with concomitant production of hydrogen peroxide. Aminopyrine (0.8 mmol/kg) also significantly increased biliary GSSG. This increase, however, was associated with a proportional increase in bile flow and in the biliary excretion of GSH such that the GSSG/GSH ratio in bile did not change. Acetaminophen and chloroform, two compounds generating electrophilic metabolites that deplete intrahepatic GSH, led to a progressive decrease in the biliary excretion of GSH and GSSG. Furosemide and dimethylnitrosamine, the electrophilic metabolites of which do not deplete hepatic GSH, minimally altered biliary GSH and GSSG. Similarly, carbon tetrachloride and iproniazid, which yield organic radical metabolites that can peroxidize membrane lipids, did not increase the biliary excretion of GSSG. This finding indicates that membrane-bound lipid hydroperoxides may not be good substrates for glutathione peroxidases. The measurement of the biliary excretion of GSSG and of the GSSG/GSH ratio in bile is a sensitive index of oxidative stress in vivo and thus complements other in vivo parameters for the study of reactive intermediates of xenobiotics such as the determination of covalent binding, the formation of lipid hydroxy acids, and the depletion of intracellular GSH.

Acetaminophen↗
PubMed1985

Role of renal metabolism and excretion in 5-nitrofuran-induced uroepithelial cancer in the rat.

5-Nitrofurans have been used in the study of chemical carcinogenesis. There is substantial evidence that N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) is deformylated to 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) in the process of FANFT-induced bladder cancer. Paradoxically, ANFT is less potent as a uroepithelial carcinogen than FANFT when fed to rats. Feeding aspirin with FANFT to rats decreases the incidence of bladder cancer. Isolated kidneys were perfused with 5-nitrofurans to determine renal clearances and whether aspirin acts to decrease urinary excretion of the carcinogen. In FANFT-perfused kidneys, FANFT was deformylated to ANFT and excreted (1.06 +/- 0.22 nmol/min) at a rate eightfold higher than excretion of FANFT. In kidneys perfused with equimolar ANFT, excretion of ANFT was 0.25 +/- 0.05 nmol/min, which suggests a coupling of renal deformylation of FANFT to excretion of ANFT in FANFT-perfused kidneys. Neither aspirin nor probenecid altered the urinary excretion or half-life of FANFT or ANFT. In rats fed 0.2% FANFT as part of their diet, coadministration of aspirin (0.5%) increased urinary excretion of ANFT during a 12-wk feeding study, which suggests decreased tissue binding or metabolism of ANFT. Kidney perfusion with acetylated ANFT (NFTA), a much less potent uroepithelial carcinogen, resulted in no ANFT excretion or accumulation, which indicates the specificity of renal deformylase. Renal deformylase activity was found in broken cell preparations of rat and human kidney. These data describe a unique renal metabolic/excretory coupling for these compounds that appears to explain the differential carcinogenic potential of the 5-nitrofurans tested. These results are consistent with the hypothesis that aspirin decreases activation of ANFT by inhibiting prostaglandin H synthase.

Administration, Oral↗