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PubMed1987

Comparative effects of ten dithiocarbamate and thiuram compounds on tissue distribution and excretion of lead in rats.

Combined treatment of rats with lead and disulfiram is known to cause increased levels of lead in brain and potentiation of the neurotoxicity of lead. Ten dithiocarbamate and thiuram compounds, including disulfiram, were compared for their efficacies in influencing tissue distribution of a trace dose of intravenously injected lead plus 203Pb in rats. The tested compounds were sodium diethyldithiocarbamate (DEDTC), sodium dimethyldithiocarbamate (DMDTC), tetraethylthiuram disulfide (disulfiram), a complex of zinc and manganese ethylenebisdithiocarbamate (mancozeb), manganese ethylenebisdithiocarbamate (maneb), sodium monomethyldithiocarbamate (metham), zinc propylene bisdithiocarbamate (propineb), tetramethylthiuram disulfide (thiram), zinc ethylenebisdithiocarbamate (zineb), and zinc dimethyldithiocarbamate (ziram). Pronounced effects on tissue distribution of lead were seen after peroral and subcutaneous administration of DEDTC, DMDTC, disulfiram, metham, thiram, and ziram. After peroral administration there was an increased uptake of lead in brain, liver, lung, and spleen and a decreased uptake in femur compared to control rats receiving only lead. Thiram was the most effective compound in enhancing lead uptake in brain, causing a 100-fold increase in 203Pb concentration at 72 hr survival. After subcutaneous administration, metham caused the highest increase in brain concentration of 203Pb. Fecal excretion of lead, which is the main excretory pathway, was decreased after peroral administration of disulfiram, ziram, and thiram to about 20% of the excretion in control rats at 48 hr. Urinary excretion of lead was significantly decreased in all the treated groups except the group treated with zineb. The effects on tissue distribution and excretion can be explained by in vivo formation of lipophilic complexes between lead and these compounds or their metabolites facilitating the transport of lead through cell membranes and the blood-brain barrier. Zineb, maneb, propineb, and mancozeb did not cause similar effects on the tissue distribution of lead. The results of this study show that interactions can occur between lead and DEDTC, DMDTC, disulfiram, metham, thiram, and ziram, resulting in increased levels of lead in brain and probably potentiation of the neurotoxic effects of lead.

Animals↗

PubMed1991

Effect of reticuloendothelial blockade on tissue distribution of 99mTc-labeled synthetic liposomes in Ehrlich solid tumor-bearing mice.

The effect of a reticuloendothelial blockade was examined on the tissue distribution of 99mTc-labeled synthetic liposomes prepared from N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) in Ehrlich solid tumor-bearing mice. While a pre-dose of unlabeled phosphatidyl choline liposomes (natural liposomes) hardly influenced the tissue distribution of N+C5Ala2C12 liposomes, the pretreatment of dextran sulfate depressed the uptake in liver accompanied by increasing that in tumor and other tissues except the stomach. However, the extent of liver depression of N+C5Ala2C12 liposomes by dextran sulfate was lower than that of natural liposomes and the pre-dose of unlabeled natural liposomes had a minor effect on the tissue distribution of N+C5Ala2C12 liposomes compared with that of natural liposomes. In the liver uptake of N+C5Ala2C12 liposomes, it was suggested that Kupffer cell phagocytosis was not the main mechanism.

Animals↗

PubMed1990

Tissue distribution of dextromoramide in the rat.

The tissue distribution of dextromoramide was studied in rats after the intraperitoneal injection of 0.2 mg/kg of the drug. The pattern of distribution was similar at 15, 30, 60 and 90 min, with the highest concentrations being found in the liver and the myocardium, while other organs were not able to concentrate dextromoramide.

Animals↗

PubMed1989

A large proportion of bovine T cells express the gamma delta T cell receptor and show a distinct tissue distribution and surface phenotype.

The numbers, phenotype, and tissue distribution of gamma delta T cells in cattle were studied using two monoclonal antibodies (mAbs) which react with the bovine gamma delta T cell receptor (TCR). Both mAbs stained 20-40% of T cells in peripheral blood, and immunoprecipitated molecules of 44 and 36 kd (reduced) and 70-80 kd (non-reduced). In cattle the majority of circulating gamma delta T cells showed a distinct surface phenotype; they expressed T19, a 215 kd molecule described in sheep and cattle which marks only gamma delta T cells. Bovine gamma delta T cells were also CD2-, CD4-, and mostly CD8-, and failed to express CD6, a molecule possibly involved in T cell activation. The distribution of gamma delta T cells in cattle lymphoid tissues differed markedly from that in humans, in that bovine gamma delta T cells were concentrated around lymph node trabeculae and were usually sparse or absent from the B cell and T cell domains of lymph nodes. Like most other species studied, gamma delta T cells in cattle were localized to epithelial surfaces, particularly within the skin and intestine, indicating that it was at these sites where gamma delta T cells functioned. Our results provide further evidence for the unusual localization, recirculation pattern, and phenotype of gamma delta T cells, and also show that some features of gamma delta T cells can differ quite markedly from species to species.

Animals↗

PubMed1979

Tissue distribution and excretion of 14c-styrene in male and female rats.

The tissue distribution and excretion of an oral dose of 20 mg/kg of 14C-styrene was studied in both male and female rats at various time intervals after administration. Peak tissue levels were attained at or before 4 hours post administration. The organ with the highest concentration of radioactivity per unit weight was the kidney, followed, in order of decreasing concentration, by the liver and the pancreas. The data suggest a relationship between tissue distribution and kidney and liver toxicity. The high levels also found in the pancreas may bear some relationship to the reported increase in glucose tolerance in workers exposed to styrene. The principal route of excretion was via the kidneys, with 90% of the dose appearing in the urine within 24 hours of administration. Less than 2% of the dose was recovered from the feces.

Animals↗

PubMed1977

Nocardicin A, a new monocyclic beta-lactam antibiotic VI. Absorption, excretion and tissue distribution in animals.

The absorption, excretion and tissue distribution of nocardicin A, a new monocyclic beta-lactam antibiotic, were studied in various animals. When nocardicin A was given intramuscularly in single doses of 20 mg/kg to rats, rabbits, and dogs, the peak serum levels of nocardicin A were about 1.6 similar to 2.8 times higher than those of carbenicillin in all animals though the levels varied among the species tested. The serum half-life of nocardicin A in these animals was about twice that of carbenicillin. The 24-hour urinary recovery rate of nocardicin A after intramuscular injection was 68.5 percent in rabbits and 77.0 percent in dogs, but was low in rats; i.e., 0.7 percent. When nocardicin A was given intravenously in single doses of 20 mg/kg to these animals, the peak serum levels varied widely among the test species; i.e. about 3 times higher than those of carbenicillin in rabbits and dogs, similar to those in rats. The peak serum and tissue levels of nocardicin A after intramuscular to intravenous injection were the highest in the kidneys, followed by the liver, serum, lungs, heart and spleen. The levels in the liver were prolonged. Nocardicin A, and traces of unknown substances less active than nocardicin A were observed as active substances in the urine recovered after injection of nocardicin A.

Administration, Oral↗

PubMed1990

Effect of cholesterol in various liposomal compositions on the in vivo toxicity, therapeutic efficacy, and tissue distribution of amphotericin B.

The effect of cholesterol in neutral, positively and negatively charged liposomes on the toxicity, therapeutic efficacy, and alteration in the tissue distribution pattern of amphotericin B (Amp-B) in normal and infected mice was studied. It was observed that inclusion of cholesterol (CHOL) into egg phosphatidylcholine (EPC) liposomes increased the LD50 of Amp-B from 5.3 to 8.5 mg/kg body weight. In the case of phosphatidylserine (PS) liposomes as well as stearylamine (SA) liposomes, cholesterol incorporation had no effect in altering the toxicity of the drug. The survival pattern of animals with all types of liposomal formulation of Amp-B was similar. The tissue distribution studies indicated that in the case of normal mice, cholesterol inclusion in all types of liposomes increased the organ concentration of the drug in various tissues. In infected animals, the concentration of Amp-B in all organs was increased when cholesterol was included in EPC and EPC/PS liposomes. The organ concentration of Amp-B in lung and liver after 1 h of injection was the same in the case of EPC/SA and EPC/SA/CHOL liposomes. Considering the observations on toxicity, therapeutic efficacy, and tissue distribution, it was suggested that cholesterol had a beneficial therapeutic effect on neutral EPC liposomes.

Amphotericin B↗

PubMed1990

Plasma clearance and tissue distribution of recombinant human platelet-derived growth factor (B-chain homodimer) in rats.

125I-labeled human recombinant platelet-derived growth factor (B-chain homodimer; rHuPDGF-BB) was intravenously injected into male rats, and plasma clearance and tissue distribution of total and acid-insoluble radioactivity were determined. Insoluble radioactivity was rapidly cleared from plasma in a biphasic manner with estimated distribution and elimination half-lives of 5.2 and 68 min, respectively. Less than 10% of the injected radioactivity remained in plasma at 1 hr after injection. rHuPDGF-BB was widely distributed throughout body tissues. However, acid-insoluble radioactive concentrations greater than those in plasma were only observed in liver, kidneys, and spleen. The radioactive concentration of most tissues declined rapidly between 1 and 4 hr but increased in the intestinal contents. Radioactive concentrations decreased in all tissues and intestinal contents at 8 and 24 hr. Urine samples collected at the latter interval showed that 39% of the dose was excreted by the kidneys in an acid-soluble form. These results suggest that the rapid clearance of rHuPDGF-BB from plasma is the result of widespread tissue distribution, metabolism by the liver, and excretion by the kidneys. In this respect, the pharmacokinetic behavior of rHuPDGF-BB resembles that of other lymphokines and growth factors that have recently been studied.

Animals↗

PubMed1986

Quantitative analysis of tissue distribution of Ly10-like murine alloantigen(s) with antisera and monoclonal antibodies.

Tissue distribution of non-Lyt1.1 ("Ly10-like") antigen or antigens encoded by short chromosomal segment differentiating B6-Ly-1a congenic strain from B6 strain of mice was studied by quantitative absorption of (BALB/c X B6)F1 anti B6-Ly-1a antiserum and by direct cytotoxicity of Ly-10-132-12-26 monoclonal antibody on lymphoid cell populations. Identical strain but not tissue distribution pattern does not allow to conclude whether antiserum and monoclonal antibody detect the same or closely linked antigens. Absorption experiments revealed the highest antigen content in the brain tissue, lower in testis and kidney, still lower in lymphoid organs and the lowest in liver and lung. Among lymphoid cells, bone marrow cells had highest absorbing capacity, followed by thymus, spleen and lymph nodes. Monoclonal antibody lysed almost 100% of thymocytes, 30% bone marrow cells and 10-20% of spleen and lymph node cells (both T-cell and B-cell enriched populations contained the same proportion of positive cells). Cortisone resistant thymocytes showed the same sensitivity as cortical thymocytes to Ly-10-132-12-26 antibody which is distinguishable characteristics of medullary thymocytes from peripheral T cells. Mitogen activated lymphocytes exhibited significantly higher expression of Ly10-like antigen than resting peripheral lymphocytes.

Animals↗

PubMed1986

Clearance and tissue distribution of fibronectin in septic rats: relationship to synthetic rate.

Fibronectin is a glycoprotein found in a soluble form in plasma and in an insoluble form in many tissues. We evaluated the influence of postoperative intraperitoneal sepsis on the clearance, tissue distribution, and synthesis of plasma fibronectin in rats (300-400 g). Experimental sepsis was induced by cecal ligation following laparotomy, whereas control animals underwent laparotomy (5 cm) alone. At 24 and 48 h after laparotomy, plasma fibronectin levels were normal. After laparotomy plus cecal ligation, plasma fibronectin increased by 47% at 24 h and remained elevated (52% above 0 time) at 48 h. At 24 h postsurgery the disappearance and tissue distribution of 75Se-plasma fibronectin and 75Se-plasma albumin was evaluated. Tissue distribution was quantified at 2 and 24 h after intravenous injection of both tracer proteins in separate groups. Both fibronectin and albumin demonstrated an initial distribution between vascular and extravascular sites and then a progressive decrease in plasma. In control (laparotomy) rats the half-life (t1/2) for plasma clearance of 75Se-plasma fibronectin was 25.33 +/- 2.53 h compared with 13.21 +/- 0.78 h in the septic rats. Septic rats manifested decreased sequestration of 75Se-fibronectin at the area of surgical incision (laparotomy), increased sequestration at the focus of intraperitoneal infection, and increased uptake in the nonviable portion of the cecum. The synthetic rate for plasma fibronectin in laparotomized control rats was 3.03 +/- 0.29 mg X 100 g-1 X 24 h-1, whereas after laparotomy plus cecal ligation the synthetic rate increased to 4.58 +/- 0.35 mg X 100 g-1 X 24 h-1. In contrast the synthetic rate for albumin decreased from 84.70 +/- 1.66 mg X 100 g-1 X 24 h-1 in controls to 52.38 +/- 1.77 mg X 100 g-1 X 24 h-1 in the septic animals. Thus intraperitoneal sepsis in the rat will enhance the vascular clearance, alter the distribution, and increase the synthetic rate for plasma fibronectin.

Animals↗

PubMedDate not supplied

The pharmacokinetics and tissue distribution of gomphoside in Wistar rats.

The excretion and tissue distribution of [3H]-gomphoside was studied after i.p. and i.v. administration of the cardiac glycoside (1 micrograms/g) to male Wistar rats. Following an intraperitoneal dosage of [3H]-gomphoside, most of the radioactivity (greater than 80%) had been excreted from the body by the end of 48 hours. Biliary excretion played a major role in elimination of [3H]-gomphoside with 90 +/- 15% of radioactivity being collected in 24 hours. Renal excretion formed a minor route of elimination of the cardiac glycoside; only 6 +/- 2% being excreted over 6 days. The distribution of radioactivity to tissues after an intravenous dose was rapid; most of the dose was located in the liver (32%), and the skeletal muscle (31%) 3 minutes after injection. The pharmacokinetics of [3H]-gomphoside could be described by a two-compartment open model with an average elimination half-life of 3.7 hours, and a large volume of distribution (2.3 +/- 0.3 ml/g body weight) characteristic of the commonly used cardiac glycosides (1).

Animals↗

PubMed1989

A minipig model of body adipose tissue distribution.

A relatively increased central (truncal) distribution of body adipose tissue has been associated with increased risk for the development of coronary heart disease in human beings. Animal models available to study this phenomenon have been limited. Validity and reliability studies of B-mode ultrasound for the measurement of subcutaneous adipose tissue thickness in miniature swine were conducted. The results showed that ultrasound measurements of subcutaneous adipose tissue thickness were accurate (+/- 0.1 cm) 95 percent of the time when compared to direct in situ ruler measurements. There was no significant systematic measurement error. Ultrasound measurements were repeatable (+/- 0.2 cm) 95 percent of the time. A computerized tomographic (CT) method to quantitate intra-abdominal adipose tissue was also developed. Serial CT measurement of total cross-sectional, density-contoured adipose tissue area correlated significantly (r = 0.91, P less than 0.01) with total intra-abdominal adipose tissue weight. This model should be useful for comparative study of the association of regional body adipose tissue distribution with the development of atherosclerotic lesions and other coronary heart disease risk factors.

Adipose Tissue↗

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↗

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↗