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PubMed1976

Phencyclidine: tissue distribution in the rat.

This study was performed to provide knowledge of the tissue distribution of phencyclidine and has demonstrated the lipophilic nature of the drug. The distribution of phencyclidine in blood, brain, and adipose tissue of rats has been determined at various time intervals during a 48-hr period. The affinity of phencyclidine for adipose tissue and the demonstration of the presence of this drug in brain tissue long after it is no longer detectable in blood provides some correlation between the tissue distribution of phencyclidine and its clinical manifestations occuring 24-48 hr after administration.

Adipose Tissue↗

PubMed1982

Manipulation of toxicity and tissue distribution of tubercidin in mice by nitrobenzylthioinosine 5'-monophosphate.

The i.v. administration of tubercidin, an analog of adenosine, in a single dose of 45 mg/kg caused death in about 90% of B10D2F1 mice so treated. Serum and urine analysis, as well as histological examination of tissues, related the lethality of tubercidin to hepatic injury, which was markedly reduced when mice were treated with the inhibitor of nucleoside transport, nitrobenzylthioinosine 5'-monophosphate (NBMPR-P), at i.p. doses higher than 10 mg/kg 30 min prior to tubercidin injection. With high NBMPR-P doses (100 mg/kg, i.p.) followed by tubercidin injection (45 mg/kg, i.v.), kidney damage and high mortality occurred. The tissue distribution of 3H following (( G-3H]tubercidin administration paralleled hepatic or renal injury: NBMPR-P treatment decreased the content of tubercidin-derived 3H in liver and increased that in kidney. Furthermore, the half-life of the decline in tubercidin levels in serum during the first minute after[3H]tubercidin administration was longer in NBMPR-P-treated mice (26 sec) than in untreated mice (10 sec), with the result that 3H levels in serum were more than ten times higher in the former than in the latter at an early stage during the distribution of tubercidin. Within 15 min after i.p. administration, the tissue distribution of (( 3H]tubercidin was complete. The i.p. administration of tubercidin caused ascites and the appearance of amylase in the peritoneal fluid evidently because of peritonitis and pancreatic injury. Administration of NBMPR-P by the i.p. route, but not by the i.v. route, prevented these injuries and shifted the LD50 of i.p. injected tubercidin (5 mg/kg) to markedly higher values (a 4-fold increase with NBMPR-P at 100 mg/kg). The protection of mice by NBMPR-P against lethal injuries caused by i.p. injected tubercidin was consistent with the inhibition by NBMPR-P of tubercidin accumulation in mesentery and pancreas. The tissue specificity of the NBMPR-P influence on the tissue distribution of tubercidin may reflect differences in NBMPR-P pharmacokinetics and/or in properties of the nucleoside permeation mechanism among various tissues.

Animals↗

PubMed1984

Tissue distribution of prednisolone in the rabbit.

The tissue distribution and kinetics of prednisolone disposition were examined in the rabbit under steady-state conditions. The steroid was infused to attain a range of plasma (362-4528 ng/ml) and tissue concentrations of pharmacologic interest. Blood components and various tissues were analyzed for prednisolone and its major metabolite, prednisone, by high-performance liquid chromatography. Unbound prednisolone was measured in plasma (percentage of binding = 72-82%) by equilibrium dialysis and tissue binding was calculated from tissue/unbound plasma distribution ratios (Kp) and fractional water content. The small intestine (Kp = 6.65), heart (2.92), kidney (2.91), lung (2.86), skeletal muscle (1.54) and spleen (1.16) exhibited linear Kp values and percentage of tissue binding. Red cell content reflected unbound prednisolone in plasma. Liver uptake (Kp = 0.38-4.47) was nonlinear with apparent tissue binding ranging from less than 59 to 84%. Slight nonlinearity occurred in prednisolone-prednisone interconversion with the liver, kidney and spleen accounting for prednisone formation. Renal clearance of prednisolone was small (6-9% of total clearance), but appreciable steroid concentrations in the bile and small intestine indicate probable enterohepatic cycling. The steady-state total and unbound plasma clearances of prednisolone were similar to those from single-dose studies. Prednisolone-prednisone interconversion and enterohepatic cycling affect the steady-state volume of distribution generated from single-dose studies as the body content/plasma concentration measure of steady-state volume of distribution is about one-half of that estimated conventionally from plasma disposition curves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1982

Whole-body retention and tissue distribution of 60Co in rats after oral administration of freshwater fish contaminated with 60Co.

The purpose of this report is to compare the whole-body retention and tissue distribution in rats of 60Co administered by gavage as inorganic 60CoCl2 or in a form incorporated into freshwater fish. Orizias latipes were placed in vessels containing 21. of tap water with radioactive cobalt. Periodically thereafter the fish were sacrificed, homogenized, and administered to rats via a stomach tube. Control groups of rats were given the radionuclide alone or together with a homogenate of nonradioactive fish. The whole-body retention and tissue distribution of the radionuclide were determined with an Armac counter. The results revealed that rats gavaged with 60Co incorporated into the fish retained much more 60Co than control rats. This trend was notable in rats given fish kept in radioactive solution for longer periods. Marked differences in tissue distribution of 60Co were also observed between rats given 60Co incorporated into fish and control rats.

Animals↗

PubMed1980

Tissue distribution and elimination of 2,8-dihydromirex in the rat.

The tissue distribution and elimination kinetics of 14C-labeled dihydromirex were investigated in the rat. Dihydromirex was distributed in all tissues examined after iv or oral administration; the highest concentrations were found in the fat, liver, and skin. The pattern of distribution was similar to that of photomirex and mirex. Elimination of dihydromirex from the blood after an iv dose was expressed by a four-compartment model, whereas fecal excretion was represented by a biphasic curve. Excretion of dihydromirex occurred predominantly in the feces; only minute amounts were found in the urine and bile. Dihydromirex constituted 90-100% of the total radioactivity in tissues and feces. No metabolite was detected.

Adipose Tissue↗

PubMed1995

Tissue distribution and deposition of clofazimine in rat following subchronic treatment with or without rifampicin.

Tissue distribution and deposition characteristics of clofazimine (CAS 2030-63-9), an antileprotic drug in rats have been investigated following controlled sub-chronic administration (p.o.) for a period of 1-2 months. The drug was administered alone at a dose of 20 mg/kg body weight and in combination with rifampicin (CAS 13292-46-1) (20 mg/kg p.o.). Various tissues (liver, lung, spleen, small intestine, brain, heart, kidney, skin, stomach and subcutaneous fat) were analyzed for clofazimine in all the treated groups. High levels (range 0.9-3.6 mg/g of wet tissue) were observed in tissues having reticuloendothelial components. In other tissues the levels were relatively lower (range 3-114 micrograms/g of wet tissue). Histopathological studies revealed that clofazimine is deposited in many tissues in the form of reddish-orange crystals. Concomitant treatment with rifampicin did not significantly alter tissue distribution or deposition profile of clofazimine nor did it influence the histopathology.

Animals↗

PubMed1986

The use of monoclonal antibodies for the species and tissues distribution of phospholamban.

Monoclonal antibodies have been raised against canine phospholamban. Two antibodies have been used in the study of phospholamban distribution in tissues, and in different animal species. The antibodies recognized the three different forms of phospholamban: non-phosphorylated, phosphorylated, and dissociated forms. A survey of nine rabbit tissues revealed that phospholamban is a cardiac muscle specific protein. Phospholamban from different mammalian hearts were found to be identical with respect to molecular weight and antigenicity.

Animals↗

PubMed1991

Use of 111In-labelling to follow tissue distribution of Candida albicans in mice.

Two strains of Candida albicans, a wild type and a derived mutant, were labelled with 111Inoxine. Labelled cells were injected into mice and tissue distribution patterns were determined from 0.5 to 48 h. During the first 4-h post-injection phase, remarkable differences in tissue distribution were observed between the two strains. Radiolabelling of C. albicans with 111Inoxine is shown to be a much more reliable method for determining early tissue distribution patterns in infected animal models than culturing the infected tissue.

Animals↗

PubMed1977

Canrenoate disposition in dogs. Tissue distribution and elimination.

The metabolism and tissue distribution of intravenously administered C14-canrenoate-potassium (CR-K) was studied at various time intervals in 10 dogs. After a rapid decline of total radioactivity immediately after injection, the elimination in plasma occurred in two distinct phases with half-lives of 6.8 and 23.6 h. Canrenoate was rapidly converted to lipid- and water-soluble metabolites which were separated by thin-layer chromatography. Most tissues showed similar concentrations of total radioactivity as plasma. An accumulation of radioactivity per g wet weight was detected in the adrenal glands and fat tissue as well as in the metabolic and excretory organs but not in the heart. Taking into consideration that skeletal muscle, fat tissue and liver constitute about 64% of the body weight, it is obvious that the main part of total radioactivity was present in these tissues. In contrast to plasma, urine and feces, where various metabolites could be analysed, the bulk of radioactivity in tissues is represented by canrenone. Thus, the estimation of the parent compound and its metabolites in plasma, urine and feces does not allow final conclusions about the active substance in various tissues. Within 72 h 47% of the dose was recovered in urine and 49% in feces.

Animals↗

PubMed1990

Comparative tissue distribution and excretion of orally administered [3H]diacetoxyscirpenol (anguidine) in rats and mice.

A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels (1.5-3.5% of dose) over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content (carcass, skin) or the absorption (stomach, small intestine), metabolism (liver), or excretion (kidney) of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific radioactivity (dpm/g tissue) instead, the carcass and skin dropped from the top rank tissues at 90 min and were replaced by the spleen and cecum. At 24 hr and 7 days the top-ranked order of tissues shifted to include organs associated with trichothecene-induced toxicity such as the lymphohematopoietic system (spleen, thymus, and femur bone marrow), heart, and testis (in mouse) as well as the cecum and large intestine. In addition, the rate of loss of radioactivity with time generally did not decrease as rapidly in these target organs as observed in liver, kidney, skin, and carcass. Brain radioactivity, though very low, also diminished relatively slowly. Significant differences in specific radioactivity which did occur between the rat and mouse tended to occur in target organs and with the higher levels present in the mouse. These data were discussed in terms of interspecies differences in lethality and target organ toxicity.

Administration, Oral↗

PubMed1986

Pharmacokinetics, renal clearance, tissue distribution, and residue aspects of sulphadimidine and its N4-acetyl metabolite in pigs.

Pharmacokinetics and tissue distribution experiments were conducted in pigs to which sulphadimidine (SDM) was administered intravenously, orally, and intramuscularly at a dosage of 20 mg SDM/kg. SDM was acetylated extensively, but neither hydroxy metabolites nor their derivatives could be detected in plasma, edible tissues or urine. Following i.v. and two oral routes of administration, the N4-acetylsulphadimidine (N4-SDM) concentration-time curve runs parallel to that of SDM. The percentage of N4-SDM in plasma was in the range between 7 and 13.5% of the total sulphonamide concentration. The bioavailability of SDM administered in a drench was 88.9 +/- 5.4% and administered mixed with pelleted feed for 3 consecutive days it was 48.0 +/- 11.5%. The renal clearance of unbound SDM, which was urine flow related, was 1/7 of that of creatinine, indicating reabsorption of the parent drug. The unbound N4-SDM was eliminated three times faster than creatinine, indicating that tubular secretion was the predominant mechanism of excretion. After i.v. administration, 51.9% of the administered dose was recovered in urine within 72 h p.i., one quarter of which as SDM and three quarters as N4-SDM. Tissue distribution data obtained at 26, 74, 168, and 218 h after i.m. injection revealed that the highest SDM concentration was found in plasma. The SDM concentration in muscle, liver, and kidney ranged from one third to one fifth of that in plasma. The N4-SDM formed a minor part of the sulphonamide content in edible tissues, in which the SDM as well as the N4-SDM concentration parallelled the plasma concentrations. Negative results obtained with a semi-quantitative bioassay method, based on monitoring of urine or plasma, revealed that the SDM concentration levels in edible tissues were in that case below 0.1 mu/g tissue.

Administration, Oral↗

PubMed1992

Endopeptidase 24-16 in murines: tissue distribution, cerebral regionalization, and ontogeny.

The tissue distribution, cerebral regionalization, and ontogeny of endopeptidase 24-16 were established in murines by means of its quenched fluorimetric substrate, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp, and its selective dipeptide blocker, Pro-Ile. Endopeptidase 24-16 was particularly abundant in the liver and kidney, and the lowest specific activity was detected in the heart. In the brain, a 16-fold difference in specific activity was observed between the poorest and the richest cerebral areas. Endopeptidase 24-16 appeared in high concentrations in the olfactory bulb and tubercule, cingulate cortex, medial striatum, and globus pallidus, and was particularly weak in the CA1, CA2, and CA3 parts of the hippocampal formation and in the cerebellum. Endopeptidase 24-16 content in thirteen thalamic nuclei indicated a rather homogeneous distribution. This homogeneity was not observed in the hypothalamus, where pronounced variations occurred between enriched zones such as suprachiasmatic and arcuate nuclei and relatively poor areas such as periventricular and supraoptic nuclei. Endopeptidase 24-16 appeared to be developmentally regulated in the mouse brain; it was already detected at the fetal stage, increased transiently after birth, then regularly declined until adulthood.

Amino Acid Sequence↗

PubMedDate not supplied

The influence of manganese on the distribution of essential trace elements. II. The tissue distribution of manganese, magnesium, zinc, iron, and copper in rats after chronic manganese exposure.

Two groups of male Sprague-Dawley rats were treated ip for 30 d with either 3.0 mg Mn/kg or an equal volume of 0.9% NaCl. Liver, kidney, pancreas, duodenum, spleen, testes, lungs, brain, skeletal muscle, bone, and blood were analyzed by atomic absorption spectrophotometry for the elements Mn, Mg, Zn, Fe, and Cu. Mn increased in all tissues except liver due to treatment. Bone and pancreas revealed the largest increases. In blood, increased Mn levels were almost totally accounted for by increases in the erythrocyte fraction. Subcellularly, all fractions (crude nuclear, crude mitochondrial, lysosomal, microsomal, and supernatant) revealed elevations in Mn content due to treatment. Mn did not concentrate selectively in any one subcellular fraction. Mn exposure was accompanied by decreased Zn levels in plasma and bone, decreased Mg levels in heart and bone, increased pancreatic Fe concentration, and increased Cu concentrations in plasma and several tissues.

Animals↗

PubMed1995

Role of the kidney in the plasma clearance of angiotensinogen in the rat: plasma clearance and tissue distribution of 125I-angiotensinogen.

We studied the tissue distribution and plasma clearance of angiotensinogen (AGN) in rats following an i.v. injection of 125I-labeled AGN. The plasma clearance rate of [125I]AGN fits a two-compartment model with half-lives of 10.2 +/- 1.5 min and 4.1 +/- 0.5 h in non-treated rats, and the half-life of slower phase significantly increased to 10.2 +/- 1.1 h following bilateral nephrectomy. Radioactivity was predominantly distributed in the kidneys (4.9%), and to a lesser extent in the liver (1.8%), testis (1.2%), spleen (0.61%), heart (0.35%), lung (0.18%), thymus (0.03%) and brain (0.03%). The subcellular distribution of radioactivity in the kidney was 64% in the soluble fraction and 33% in the crude mitochondrial-lysosomal fraction. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed that the radioactivity in the soluble fraction consisted of proteins corresponding to intact [125I]AGN, whereas the mitochondrial-lysosomal fraction contained additional radioactive proteins with molecular weights between 18,000 and 29,000. When isolated kidney cells were incubated with [125I]AGN at 0 degree C, the radioactive binding was saturable and specific with a Kd value of 4.8 x 10(-11)M, whereas incubation at 37 degrees C resulted in the appearance of degraded products of [125I]AGN in the medium. These results suggested that circulating AGN is cleared mainly by the kidneys via receptor-mediated endocytosis, which may play an important role in regulating plasma level of AGN.

Angiotensinogen↗

PubMed1991

Adipose tissue distribution changes during rapid weight loss in obese adults.

Changes in adipose tissue distribution as defined by the waist-to-hip ratio (WHR), were evaluated in 16 android, obese subjects (seven male and nine female) given a very low energy ketogenic diet of 1.72 MJ (411 kcal) for 4 weeks. Total weight loss was significantly greater for the males (11.2 +/- 2.5 kg) compared to females (8.3 +/- 0.8 kg); the relative weight loss however, was similar (9.9 vs 9.3 percent). Female and male losses in percent body fat and lean body mass were not significantly different. For both groups, significant (P less than 0.01) changes in waist and hip circumferences were observed; however, no significant changes were observed in WHR. These results indicate that in obese android male and female subjects, adipose tissue distribution as measured by WHR, does not change in response to rapid weight loss.

Adipose Tissue↗

PubMed1978

Cell and tissue distribution of 14C-labeled pyran copolymer.

The tissue distribution of pyran (maleic anhydride-divinyl ether) copolymer was studied after a single ip injection of 14C-labeled pyran (25 mg/kg) to mice. The pyran showed a reticuloendothelial distribution with the liver and spleen containing the highest concentrations which persisted for at least 21 days after drug treatment. Blood levels of 14C-pyran reached a peak 2 hours after injection and were cleared within 6 hours. Attempts to measure uptake of 14C-pyran by peritoneal macrophages were unsuccessful due to an inability to recover macrophages between 3 and 24 hours after ip pyran administration. Since activated macrophages appear to be the primary mechanism by which pyran enhances host resistance to microbial infection and neoplasia, the uptake of 14C-pyran by isolated peritoneal macrophages in vitro was studied. Purified macrophages showed a gradually increasing uptake of 14C-pyran, and a large amount of cell-associated radioactivity was bound to trichloroacetic acid-precipitable material. Several polyanions, including unlabeled pyran, dextran sulfate, and poly(I)-poly(C), competed for acid-precipitable receptor molecules. The superior antitumor effects of pyran as compared to other polyanions may result from the continuous presence of the synthetic polymer in the host. Possible mechanisms of immunopotentiation by pyran are discussed.

Animals↗

PubMed1984

Glucose dehydrogenase in teleosts: tissue distribution and proposed function.

Tissue extracts of skeletal muscle, heart, eye, brain, liver, kidney, gill and stomach were electrophoretically examined for glucose dehydrogenase (EC 1.1.1.47) activity in 21 species of marine teleost fishes. Glucose dehydrogenase expression was detected only in liver extracts. Considerable interordinal variation was found in levels of enzymatic activity. Available data support the hypothesis that glucose dehydrogenase provides NADPH for the mixed-function oxidase system in teleosts.

Animals↗

PubMed1986

Alcohol dehydrogenase isozymes in baboons: tissue distribution, catalytic properties, and variant phenotypes in liver, kidney, stomach, and testis.

Isoelectric focusing and cellulose acetate electrophoresis were used to examine the multiplicity, tissue distribution, and variability of alcohol dehydrogenase (ADH) among baboons, a primate species used as a model for research on alcohol metabolism and alcohol-induced liver pathology. Five major ADH isozymes were resolved and distinguished on the basis of their isoelectric points, tissue distributions, relative activities with alcohol substrates, and sensitivities to inhibition with 4-methyl pyrazole. ADH-1 and ADH-2 exhibited class I kinetic properties and were observed in high activity in kidney and liver extracts, respectively. ADH-3 showed class II kinetic properties, exhibiting high activity in stomach extracts, and was widely distributed in extracts of other baboon tissues, including kidney, esophagus, heart, testis, brain, and male sex accessory tissues. ADH-4 also showed class II ADH properties but was found only in liver (similar to human "pi-ADH"). ADH-5 exhibited class III ADH kinetic properties, being inactive with ethanol up to 0.5 M (similar to human "chi-ADH") and was distributed widely in baboon tissue extracts. Major activity variation was observed for liver ADH-4 between different animals. An electrophoretic variant for ADH-3 was observed for the enzyme in stomach, kidney, and testis extracts, and activity variation existed for this isozyme in kidney extracts. It is apparent that baboon ADH shares a number of features with the human ADH phenotype; however, several species-specific differences were observed, particularly for the liver and kidney class I isozymes and for stomach ADH.

Alcohol Dehydrogenase↗