Absorption, excretion and tissue distribution of natural organic and inorganic zinc-65 in the rat.

The absorption and tissue distribution of organic and inorganic forms of 65-Zn were studied in the rat following single tracer oral doses. Rats dosed with 65-Zn grown into young corn and rye plants (organic form) absorbed and retained more 65-Zn in tissues than those given 65-Zn mixed with tissue paper (inorganic forms). A part of the beneficial effect was evident when 65-Zn was mixed with forage. The relatively high absorption values indicate that both forms were readily available, and thus incorporating zinc into young forage protein is not of major practical importance.     

Tissue distribution of L-fucokinase in rodents

L-fucose (fucose) is a monosaccharide normally present in mammals and is unique in being the only levorotatory sugar that can be synthesized and utilized by mammals. The metabolism of fucose is incompletely understood, but fucose can be synthesized de novo or salvaged. The utilization of fucose in the salvage pathway begins with phosphorylation by fucokinase. As part of an investigation of fucose metabolism in normal and disease states, we began an investigation of this enzyme. In this report, we present the tissue distribution of the enzyme in rat and mouse. The highest amount of activity was present in brain of both species. Some activity was found in all tissues examined (liver, kidney, heart, lung, spleen, brain, muscle, thymus, white adipose, testes, eye, aorta, small intestine, and submaxillary gland). Very low levels were found in small intestine. Varying levels in the tissues seems most likely to be the result of varying amounts of fucokinase protein as no difference in the Km values of crude enzyme could be shown. Protein-bound fucose levels were determined using the L-cysteine-phenol-sulfuric acid (CPS) assay. There is not a good correlation between fucokinase activity and protein-bound fucose, suggesting some tissues are more active in synthesis of fucose than others.     

Dose-linear pharmacokinetics, tissue distribution, and excretion of a recombinant fusion protein 125I-GST-TatdMt possessing potent anti-obesity activity

This study first examined the pharmacokinetic disposition of GST-TatdMt, a recombinant Tat protein possessing potent anti-obesity activity, in rats after i.v. injection. GST-TatdMt was over-expressed in E. coli, purified, and radioiodinated using the IODO-GEN method. The radioiodinated 125I-GST-TatdMt was administered to rats at doses of 9 microg (1640 nCi), 18 mug (3388 nCi), and 35 microg (6420 nCi). Upon administration, the total radioactivity in serum declined bi-exponentially, with the average terminal elimination half-life ranging from 13.7 to 15.7 h. There was a linear relationship between dose and AUC(INF) (r2=1.000) and between dose and Co (r2=0.999). The fraction of administered radioactivity excreted in feces was low (mean range 1.5-2.8%), while the majority of the radioactivity was excreted in urine (mean range 54.9-61.4%). The radioactivity found in the liver, lungs, spleen, and kidneys were higher than in serum, but the tissue-to-serum ratios were relatively low (<1.64). The radioactivity in testes, adipose tissue, heart, and brain was lower than in serum (tissue-to-serum ratios 0.046-0.27). The findings of this study indicate dose-linear pharmacokinetics of 125I-GST-TatdMt in rats over the i.v. dose range studied.     

Pharmacokinetic and tissue distribution study of [14C]fluasterone in male Beagle dogs following intravenous,oral and subcutaneous dosing routes

The purpose of this work was to compare the pharmacokinetics (PK) and tissue distribution of [¹⁴C]fluasterone following intravenous (iv), subcutaneous (sc) and oral (po) administration in male Beagle dogs. The main goal of the investigation was to discover if non-oral routes would alter parameters observed in this study following the administration of [¹⁴C]fluasterone. The oral formulation had a lower bioavailability (47%) compared to the sc formulation (84%). Po and sc administration resulted in a similar t_max; however, the observed C_max following sc dosing was less than half of that after oral dosing. The sc route had the greatest overall exposure (AUC_0–∞). Tissue distribution analysis 2 h post-intravenous dosing showed that connective tissue (adipose and bone), liver, and skeletal muscle accumulated relatively high levels of fluasterone. The majority of the dose was retained during the first 24 h. Elimination of [¹⁴C]fluasterone-derived radioactivity following intravenous dosing resulted in urine and feces containing 7.6% and 28%, respectively, of the total dose over the first 24 h. Elimination of [¹⁴C]fluasterone-derived radioactivity following subcutaneous dosing resulted in 4.6% in urine and 7.8% in feces of the total dose over the first 24 h. Following oral dosing, elimination resulted in 3.8% in urine and 36% in feces over the first 24 h. In conclusion, the sc route of administration offers some advantages to po and iv due to the prolonged release and increased retention through 24 h.     

Inhibitory effect of ginsenoside-Rd on carrageenan-induced inflammation in rats

A previous study reported that ginsenoside-Rd reduced the production of tumor necrosis factor-α by inhibiting nuclear factor-κB in lipopolysaccharide-activated N9 microglia in vitro. The aim of the present study was to confirm the anti-inflammatory effects and mechanisms of ginsenoside-Rd in animal experiments involving acute inflammation. The results indicated that ginsenoside-Rd at doses ranging from 12.5 to 50?mg/kg i.m. significantly inhibited the swelling of hind paws in rats for 1-6?h after the carrageenan injection. The levels of proinflammatory cytokines and proinflammatory mediators were markedly reduced by ginsenoside-Rd. Ginsenoside-Rd, when administered intramuscularly at 12.5, 25, and 50?mg/kg doses, showed signicant inhibition of carrageenan-induced production of interleukin-1β (6.91%, 45.75%, and 55.18%, respectively), tumor necrosis factor-α (37.99%, 56.39%, and 47.38%, respectively), prostaglandin E(2) (22.92%, 30.12%, and 36.36%, respectively), and nitric oxide (28.27%, 44.53%, and 53.42%, respectively). In addition, ginsenoside-Rd (12.5, 25, and 50?mg/kg i.m.) effectively decreased the levels of nuclear factor-κB (6.77%, 20.28%, and 41.03%, respectively) and phosphorylation of IκBα (13.23%, 26.92%, and 41.80%, respectively) in the carrageenan-inflamed paw tissues. These results suggest that ginsenoside-Rd has significant anti-inflammatory effects in vivo, which might be due to its blocking of the nuclear factor-κB signaling pathway. Thus, it may be possible to develop ginsenoside-Rd as a useful agent for inflammatory diseases.     

The distribution of plutonium-214 in rodents.

Plutonium-214 citrate solution at pH 6-5 was injected intravenously or intra-peritoneally into hamsters and rats at a dose of 50 MBq kg-1 (1-35 mCi kg-1). The animals were killed 1 day or 1 week later, and tissues were removed for autoradiography and radiochemical analysis. Plutonium-241 was distributed in rats in the same way as plutonium-239, and is a suitable isotope for high-resolution tissue-section autoradiography. Plutonium deposits in cells consisted of a nuclear and a cytoplasmic component. In the hamster kidney cells, the amount associated with the nucleus was about 55 per cent of the total cellular plutonium at 24 hours after injection. Six days later, it was only about 30 per cent. Plutonium deposits were also characterized in hepatocytes, in the interstitial cells of the testes, in the cells of ovarian follicles, in chondrocytes and in bone cells, including osteoblasts and osteocytes. In bone there appeared to be both an extracellular and intracellular deposit. No evidence was found of substantial incorporation of plutonium into the mineral phase of bone.     

Serum half-life, distribution, hepatic uptake and biliary excretion of alpha-tocopherol in rats

The serum clearance of alpha-[3H]tocopherol has been studied after intravenous injection of intestinal lymph labeled in vivo with radioactive alpha-tocopherol. The half-life of the injected alpha-[3H]tocopherol was approx. 12 min. Fractionation of plasma by ultracentrifugation 10 min after injection of lymph showed that 91% of the radioactive alpha-tocopherol remaining in plasma was located in chylomicrons (d less than 1.006 g/ml) and 7.8% in high-density lipoproteins (HDL, 1.05 less than d less than 1.21 g/ml). 2 h after administration of alpha-tocopherol, about 35% of the radioactivity recovered in plasma was associated with chylomicrons and approx. 51% with HDLs. alpha-[3H]Tocopherol was initially taken up by the liver, which contained more than 50% of the injected radioactivity after 45-60 min. Separation of parenchymal and nonparenchymal cells demonstrated a preferential uptake of alpha-[3H]tocopherol by the parenchymal liver cells. After 24 h about 11% of the injected dose was recovered in the liver. Considering whole organs the liver, adipose tissue and skeletal muscle had the highest content of radioactivity after 24 h. Furthermore, about 14% of the administered dose was recovered in bile during 24 h draining.     

The gastrointestinal absorption,tissue distribution,urinary excretion and metabolism of N-(2-aminoethyl)-glycine (AEG) in the rat

Radiolabeled N-(2-aminoethyl)-glycine (AEG) was synthesized and various aspects of its bioavailability were evaluated. AEG was rapidly and completely taken up by the small intestine of the rat. It was quickly absorbed into the portal vein. Most of the absorption took place during the first hour, with a peak at 30 min. Entry of this compound into the intestinal mucosal cell may be by a mechanism not involving active transport. Of many organs examined, only the liver took up significant amounts of AEG. The latter neither crossed the brain barrier nor was metabolized. Total urinary excretion (as intact AEG) averaged 80% of the administered dose within 4 hours and nearly 100% by 10 hours. Excluding the neutral-acidic amino acids and ammonia, AEG represented >99% of the ninhydrin positivity in the urine. AEG is thus an example of a substance which is rapidly and totally absorbed, as well as quickly and completely excreted.