Excretion Of 51Cr Research Articles

Study on the metabolism of physiological amounts of Cr(III) intragastrical administration in normal rats using activable enriched stable isotope Cr-50 compound as a tracer

In order to study the metabolism of physiological amounts of51Cr (10 μg/100 g of body wt.) intragastrically administered in rats, the activable enriched stable isotope Cr-50 compound Cr2O3 was used as a tracer. The absorption and distribution of51Cr(III) in rats with time were studied. Significant51Cr contents were found in all the organs and tissues of interest. The kidney, liver and bone contain higher amounts of51Cr than others. The fact that specific activities of51Cr are notably high in kidney, bone, spleen and pancreas and decrease gradually with time suggests that there are tighter binding of chromium in these organs. The excretion of51Cr at various time intervals was also studied. Almost totally intragastrically administered dose was excreted in the feces. The increased urinary excretion of51Cr with time indicates that the urine-chromium is the metabolic derivative of organism. In view of the tissues distribution and excretion, it can be concluded that no more that 1% of the dose was absorbed from the gastrointestinal tract.

Use of the enriched stable isotope Cr-50 as a tracer to study the metabolism of chromium (III) in normal and diabetic rats.

The activable enriched stable isotope Cr-50 compound Cr2O3 was used as a tracer to study the metabolism of chromium(III) [CR(III)] intragastrically administered in normal and diabetic rats. The comparison of absorption, distribution, and excretion in organs and tissues of the two groups do not show much alteration, but some differences exist indeed. The contents of 51Cr radioactivity of the diabetic rats appear to be of higher retention than in most studied organisms. The urinary 51Cr excretion of diabetics is significantly higher than that of normal rats. Therefore, a conclusion can be drawn that the insulin-dependent rats generally absorb and excrete more chromium (Cr) than the normal rats.

Absorption, Retention and Urinary Excretion of Chromium-51 in Rats Pretreated with Indomethacin and Dosed with Dimethylprostaglandin E2, Misoprostol or Prostacyclin

Drug-nutrient interactions affecting chromium were investigated in this study. Rats were injected with indomethacin to reduce endogenous prostaglandin synthesis and dosed with prostaglandin analogues or prostacyclin. Effects on absorption, tissue distribution and urinary excretion of 51Cr from 51CrCl3 were evaluated using a 2 x 4 factorial experimental design. Forty-eight adult male rats were food deprived for 12 h and then injected intraperitoneally with indomethacin (5 mg/kg body wt) or placebo. Thirty minutes later, rats were intubated and dosed with one of four treatments: a prostaglandin E1 analogue (misoprostol) at 50 microg/kg body wt; a prostaglandin E2 analogue (16,16-dimethylprostaglandin E2) at 7.5 microg/kg body wt; prostacyclin at 20 microg/kg body wt; or control (7.64 mmol/L Tween-80 suspended in 0.15 mol/L NaCl containing 0.48 mol/L ethanol). Immediately after intubation, rats were dosed with 3.7 mBq of 51CrCl3 by micropipette. Blood was collected from the tail at intervals after 51Cr dosing. Six hours after dosing, 51Cr rats were exsanguinated by cardiac puncture. Indomethacin, an inhibitor of prostaglandin synthesis, significantly increased (P < 0.05) 51Cr in blood at all time periods tested except at 15 min. In tissues, indomethacin significantly increased 51Cr retention. Urinary 51Cr excretion at 6 h was higher (P < 0.05) in indomethacin-pretreated rats than in control rats. Administration of indomethacin, which blocks prostaglandin synthesis, enhanced 51Cr absorption, whereas dosing with 16,16-dimethylprostaglandin E2 decreased 51Cr absorption.

Gastrointestinal transit, absorption and tissue retention of 51chromium in control and streptozotocin-induced diabetic rats

Gastrointestinal transit, absorption, tissue retention and urinary excretion of 51Cr from 51CrCl 3 were investigated in control and streptozotocin (STZ)-induced diabetic rats. Animals were held a minimum of six weeks after STZ injection before the experiment. After an overnight fast, animals were dosed orally with 10 μCi of 51CrCl 3 and sacrificed 2 hr thereafter. Radioactive chromium was counted in selected organs, blood, urine, segmented small intestine, and digested stomach, colon, and cecum. Results indicated that the absorption of 51Cr from 51CrCl 3 was low in both treatment groups. The gastroinestinal transit of 51Cr was slower in diabetic than control rats, but blood concentrations, tissue retention and urinary excretion of 51Cr were not significantly influenced by the diabetes.

Uptake and retention in suckling rats of 51chromium fed with human milk or infant formulas.

Optimum concentration of Cr for infant formulas has not been established. Such components as soy protein or supplemental Fe could influence absorption and retention. Suckling rat pups were used to evaluate the influence of three commercial formulas and human milk, all of which had been incubated with 51CrCl3 for 1 h, on the uptake and retention of the added 51Cr. After fasting 3 h, the pups were intubated with a single dose of 25 microCi 51CrCl3 in either a cow's milk-based formula, an Fe-supplemented cow's milk-based formula, a soy-based formula, or human milk. Six hours later, 51Cr was counted in five organs, thymus, blood, and total urine. Absorption of 51Cr was low. At 6 h, percent 51Cr in blood was < 0.2% of the dose, and total 51Cr excretion in urine was < 1.8%. The uptake and retention of 51Cr and its concentration in any of the organs, thymus, blood, and urine were not influenced by different types of formula or by human milk.

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Fecal Excretion of Radiolabeled (51CrCl3) Proteins in Patients with Crohn's Disease

Intestinal leakage of plasma proteins was studied in 69 patients with Crohn's disease. In vivo labeling of plasma proteins was performed by intravenous injection of trace amounts of 51CrCl3. Complete fecal collection was done for 5 days, carefully avoiding contamination with urine. The daily fecal radioactivity was measured in a whole-body counter and expressed as a percentage of given dose. In patients with a classic localization of the disease the mean fecal excretion of radiolabeled proteins was 2.8% (range, 0.8-5.5%). The excretion was significantly higher in patients with extensive ileojejunal involvement (8.8%; 4.3-14.0%) and in patients with a total colitis (5.5%; 2.0-8.2%) but not different from that in patients with prestomal recurrent ileal disease (3.5%; 1.6-5.3%). A close correlation was found between fecal excretion of 51Cr and extent of the small-intestinal disease as measured at laparotomy (r = 0.86, p less than 0.001). A highly significant inverse relationship was also demonstrated between fecal protein excretion and serum albumin concentration in patients without septic complications of the disease (r = -0.57, p less than 0.001). A pre-existing septic complication made the patients hypoalbuminemic despite limited intestinal loss of protein. It is concluded that estimation of intestinal protein loss is a sensitive and simple test for assessment of the extent of the small-intestinal involvement in patients with Crohn's disease. The test may be of value in patients with unclear radiologic findings and in patients with hypoalbuminemia of unknown cause.

Radionucleide tests for the assessment of intestinal permeability

14C labelled-D-mannitol and aquo (ethylene-diaminetriacetoacetic acid) 51chromium (III) (51Cr EDTA) have been evaluated as markers of intestinal permeability in twenty-four healthy control subjects, sixteen patients with recently diagnosed coeliac disease and twenty subjects with coeliac disease in remission on a gluten-free diet. The percentage excretion of 14C mannitol in urine collected for 6 h was significantly less in patients with coeliac disease (mean 6.7%) than controls (mean 13.5%). Conversely the excretion of 51Cr EDTA was significantly greater in patients with coeliac disease (mean 1.23%) compared with controls (mean 0.28%). The mean ratio of the percentage excretion of 51Cr to the percentage excretion of 14C was 0.29 in patients with untreated coeliac disease compared with 0.023 for healthy control subjects (P less than 0.001). Patients with untreated coeliac disease were clearly separated from control subjects by use of the 51Cr EDTA: 14C mannitol ratio but not by the excretion of independent markers.

Radiochromium distribution during saline diuresis.

Free water diuresis in vasopressin-deficient Brattleboro rats does not influence body conservation of chromium (Cr+3), suggesting a proximal tubular site for renal Cr reabsorption. Other data suggest that Cr conservation is accomplished primarily by lack of glomerular filtration or by tissue binding to a specific Cr-binding substance. To provide further data, radiochromium (51Cr) retention and tissue distribution were studied in SHR and WKY rats undergoing saline diuresis. Despite high urine flows, body retention and urinary excretion of 51Cr were unchanged. Tissue content of 51Cr was minimally and not consistently influenced by saline diuresis in either rat strain. Compared to WKY rats, the SHR rats had a trend to lower serum and tissue 51Cr content but higher tissue/serum 51Cr ratios. These data fail to incriminate collecting duct reabsorption in Cr conservation but are compatible with proximal Cr reabsorption or either of the two hypotheses mentioned above. The decreased serum 51Cr content of SHR rats may be due to the mechanical effect of increased plasma and extracellular volumes. One possible explanation for the increased tissue/serum 51Cr ratios may be the presence of a factor in SHR rats promoting cellular Cr transport. However, there is no present evidence to suggest that any of the hormones believed capable of increasing Cr transport (insulin, growth hormone, thyroxine, ADH) are increased in the SHR rat.

The effect of chronic ingestion of lead on gastrointestinal transit in rats

GI symptoms such as constipation and abdominal colic are signs of lead poisoning in man, but mechanisms of these effects have not been elucidated. To evaluate GI transit, male Wistar rats were dosed with 1% lead or 0.7% sodium acetate in their diet (AIN-76A). After 7 weeks, lead-treated animals exhibited decreased hematocrit, increased 24-hr urinary excretion of δ-ALA, increased kidney/body weight ratio, and decreased body weight. Blood-lead concentrations were elevated to 196 ± 57 μg/dl. Lead treatment, however, did not result in change in GI transit of a nonabsorbable marker, 51Cr, 15 min or 6 hr after po administration. These was also no change in fecal percentage water content. Since in control animals the semipurified diet AIN-76A markedly decreased fecal excretion rate of 51Cr compared to a cereal-based diet, NIH-07, the latter was used in subsequent experiments. Rats fed 2 or 4% lead acetate in NIH-07 for 8 weeks exhibited renal and hematologic toxicity as in the initial experiment. Weight gain was impaired in the 4% group compared to pair-fed controls. No significant differences were observed in the 1-hr gastric emptying or the fecal excretion of 51Cr in the 2 or 4% lead-treated animals, although there was a trend for slower transit in rats receiving the higher dose. These observations indicate that concentrations of lead sufficient to induce renal and hematologic toxicity in rats do not substantially affect GI transit.

Difference in the metabolic patterns of Cr III and Cr VI ions in the rat

Different aspects of the biochemistry of chromium in laboratory animals have been investigated using 51Cr radiotracer methods. 51Cr-labelled chromium compounds such as cationic trivalent 51Cr 3+ and anionic hexavalent 51Cr 6− were prepared and administered I.V. to rats in doses ranging from 0.1 to 100 μg/rat. The results show remarkably different metabolic patterns in the two chemical species. They refer (1) to the distribution in the blood. More than 95% of the 51Cr in the blood of rats administered with the trivalent form was present in the plasma while the corresponding value in the case of the hexavalent species was of about 25%. Gel permeation chromatography on sephadex G-150 and ion exchange chromatography in DEAE show that the 51Cr plasma of rats treated with 51Cr 3+ is associated with β-globulin transferrin. Dialysis experiments indicate the strong nature of the binding of chromium to transferrin. They also refer (2) to the biliary excretion patterns. The biliary excretion of 51Cr has been studied in the bile duct-cannulated rats 120 min after the intravenous administration of 0.1 μg Cr/rat to 100 μg Cr/rat as trivalent or hexavalent chromium. The biliary levels of 51Cr-derived radioactivity reached their peak 30 min after injection of both Cr III and Cr VI and decreased slowly thereafter. The 2 hour biliary concentrations of Cr in the animals treated with Cr VI were up to 60 times higher than those found in the rats given the same amount of the trivalent Cr form 2.6 per cent of the dose was recovered in the bile of rats injected with Cr VI within 2 hours while the 2 hours cumulative excretion of 51Cr in the bile of Cr III treated animals was approximately 50 times lower. In the first 120 min period after treatment of the bile-fistula rats the urinary excretion of 51Cr ranged from 7 to 15% of the administered dose without any obvious relation to the chemical form and the dosage level. Chromium had no effect on the rate of biliary flow. The plasma levels of 51Cr-radioactivity of the animals treated with Cr VI were significantly lower than those detected after injection of the same doses of Cr in the trivalent form. No valency-related differences were found with respect to the liver concentrations of 51Cr labelled chromium. These findings indicate that the distinctive pattern of Cr biliary excretion observed in the rat after treatment with Cr III and Cr VI are independent of the plasma-to-bile and liver-to-bile concentration gradients of this chemical species. In this study, evidence has also been obtained for a direct excretion of Cr across the intestinal wall as indicated by the presence of appreciable levels of 51Cr activity in feces in the gastrointestinal segments of rats with ligated bile duct after intravenous injection of 100 μg of 51Cr-labelled chromium. Average values of 4% and 1.5% of the injected Cr dose were measured in the gut(stomach and intestine plus contents) 24 hrs after the injection of Cr VI and Cr III, respectively. This findings provided further support for the concept that the trivalent and hexavalent forms of Cr exhibit different behaviour in their elimination patterns by the digestive tract.

Gastrointestinal protein loss in the nephrotic syndrome studied with 51Cr-albumin.

Gastrointestinal protein loss was studied by intravenous application of 51Cr-albumin and the measurement of fecal excretion of 51Cr. As compared to controls, fecal excretion of 51Cr was largely increased in 28 patients with nephrotic syndrome due to glomerular disease and in 11 patients with hypoproteinemia in the course of different gastrointestinal disorders. It was not increased in nephrotic patients without primary glomerular disease and in renal insufficiency without nephrotic syndrome. Controversial data of the literature are discussed with regard to different methods and patient groups.

Albumin metabolism and gastrointestinal loss of protein in chronic renal failure.

The catabolism of albumin labelled with 125I has been studied in 10 patients with advanced renal failure and in 5 with nephrotic syndrome. In 10 patients the gastrointestinal protein loss was studied simultaneously by determing the faecal excretion during 7 days of 51Cr after i.v. administration of 51Cr-labelled chromic chloride. The results were related to a control group in which 12 subjects were studied with respect to albumin catabolism and 17 with respect to the gastrointestinal protein losses. The results showed that: 1) In the two patient groups the means for serum albumin concnetration and the intravascular albumin pool, expressed as g or g/kg b.wt., were significantly decreased compared with those of the control group. 2) The two patient groups had an increased extravascular albumin pool as well as an elevated ration between extra- and intravascular pools. 3) The mean albumin catabolic rate was not increased in the renal insufficiency group, expressed as a percentage of the intravascular pool/24 h or as g/24 h. In the patients with nephrotic syndrome, however, it was significantly increased. 4) The renal insufficiency group had a mean cumulative 51Cr excretion during 7 days of 1.6+/- 0.80% of the given dose, the control group 0.63+/- 0.30%. This difference is highly significant. The patients with nephrotic syndrome did not differ from the control group.

Patho-physiology of ovine schistosomiasis: VI. Onset and development of anaemia in sheep experimentally infected with Schistosoma mattheei— Ferrokinetic studies

The erythropoietic response of sheep to infection with Schistosoma mattheei was monitored by serial measurements of plasma iron turnover and red cell 59Fe utilization rates in 8 animals over a period of 16 weeks following exposure of each to 10 000 cercariae; 4 worm-free sheep were similarly studied. Strong evidence that dyshaemopoiesis acts as an important contributory factor in the development of ovine schistosomal anaemia was provided by the fall in plasma iron turnover and the slower rate of incorporation of 59Fe into red cells recorded for infected sheep between the 4th and 8th weeks after exposure to cercariae. Subsequent measurements of these parameters of red cell production revealed no significant differences between infected and worm-free animals despite the considerable depletion of haemoglobin and red cell mass suffered by the infected group following the onset of intestinal haemorhage; these findings suggest that impairment of marrow reserve capacity increases the severity of the haematological disturbances associated with ovine schistosomiasis. The ability of sheep to re-utilize iron passed into the gut was estimated from the faecal excretion of 51Cr and 59Fe after simultaneously tagging the erythrocytes with these isotopes. It was found that both normal and infected animals were generally unable to re-utilize significant amounts of such iron, suggesting that in severe or long-standing infections iron could become a limiting factor in erythropoiesis.

Urinary Excretion of 51Cr From Labeled Erythrocytes

The urinary excretion of radioactive chromium ( 51 Cr) can be used as an index of erythrocyte survival, using washed erythrocytes labeled with 51 Cr, in a study period of four days. This method also appears to be a better index of erythrocyte destruction than the conventional erythrocyte survival measurement because the 51 Cr activity in the urine is a function only of the rate of in vivo destruction and elution of labeled erythrocytes, and data obtained from excretion of 51 Cr show virtually no dispersion from a simple exponential curve. The dose can be decreased to 10 microcuries or less and the amount of labeled blood injected can be as little as 1 ml. This method has a potential for use in in vivo compatibility testing of donor blood.

The kinetics of urinary excretion of 51Cr from labeled erythrocytes in hemolytic anemia and the anemia of blood loss.

The urinary excretion of 51Cr was studied in conjunction with studies of erythrocyte survival, fecal blood loss, and erythrocyte volume in 54 patients with various hematologic disorders. It was confirmed that excretion of 51Cr is predominantly urinary, and the rate approximates a simple exponential function. In anemias unaccompanied by hemolysis or blood loss, the halftime for urinary excretion of erythrocyte-bound 51Cr (Tu½) ranged from 43 to 63 days. Tu½ was shortened in patients with hemolytic disease but prolonged in patients with severe blood loss; these deviations were proportional to the severity of hemolysis or blood loss, respectively. Determination of the rate of urinary 51Cr excretion may prove to be useful in differentiating various causes of anemia, especially because (1) it distinguishes severe or chronic blood loss from hemolysis, which is not possible with conventional erythrocyte survival studies; (2) the need for multiple venipunctures may be obviated; (3) fluctuations in blood volume or erythrocyte volume do not appear to affect the rate of urinary 51Cr excretion; (4) only a very small dose of radiochromium is needed.

Ferrokinetic studies on normal and fluke-infected rabbits

The disappearance of radioiron from the plasma and its subsequent incorporation into red cells was studied in normal and fluke-infected rabbits. The results of these experiments show that erythropoiesis, as measured by the rate of removal of radioiron from the plasma and its subsequent incorporation into red cells, is greatly increased in fluke-infected relative to normal animals. As with 51Cr-labelled red cells, a considerably shortened half-life of red cells labelled with 59Fe occurs in infected animals, this being associated with an increased faecal excretion of the isotope, and hence of haemoglobin iron. The ability of the rabbit to re-utilise iron passed into the gut was estimated from the faecal excretion of 51Cr and 59Fe after simultaneously tagging the erythrocytes with these isotopes. It was found that both normal and infected animals were unable to re-utilise such iron. This was confirmed by following the faecal excretion of an oral dose of lysed red cells labelled with 51Cr and 59Fe.

The site of abnormal erythrocyte destruction during experimental fever.

Measurement of the 51Cr activity in the whole body, blood, and reticulo‐endothelium system organs in rabbits, exposed to a period of fever by injection of bacterial pyrogen after labelling of the erythrocytes, showed:(1) 51 Cr, liberated by normal or abnormal erythroclasis, is temporarily deposited in an extravascular site. Under normal conditions the spleen and bone marrow are the main organs where the deposition occurs.(2) The abnormal erythrocyte breakdown during fever immediately gives rise to an increased excretion of 51Cr in the urine. Simultaneously, there is a significant increase in the activity in the spleen. Five days after a 5‐day period of fever, about 40 per cent of the abnormal 51Cr loss from the blood was recovered in the spleen. There were no signs of intravascular haemolysis.(3) The presence of increased haemoglobin in the splenic tissue of the fever‐exposed rabbits and the absence of abnormal erythrocyte loss during pyrexia in splen‐ectomized rabbits indicate that the spleen plays a direct role in the abnormal loss. The pathogenesis of the cell loss is discussed.

Use of 125-I- and 51-Cr-labeled albumin for the measurement of gastrointestinal and total albumin catabolism.

A method for the simultaneous measurement of gastrointestinal protein loss and total albumin turnover entailing the use of a combination of (125)iodine- and (51)chromium-labeled albumin is described. Albumin turnover was calculated by the measurement of albumin-(125)I plasma decay and cumulative urinary excretion, and the results obtained agreed closely with previous studies utilizing albumin-(131)I. Gastrointestinal catabolism was calculated from the rate of fecal excretion of (51)Cr and the specific activity of plasma albumin-(51)Cr, and these data were related to the calculated albumin turnover results. During the period of 6-14 days after administration, the ratio of specific activties of albumin-(125)I and -(51)Cr in plasma and in extravascular spaces or gastric and biliary secretions remained almost identical. Fecal excretion of (51)Cr was also quite stable at this time. In six normal subjects gastrointestinal catabolism accounted for less than 10% of total albumin catabolism. Excessive gastrointestinal protein losses did not contribute to the low serum albumin in three patients with cirrhosis or in two adults with the nephrotic syndrome. Multiple mechanisms leading to hypoalbuminemia were demonstrated in other subjects with a variety of gastrointestinal disorders.