Copper-Metallothionein Metabolism in the Kidney of Brindled Mice

Prins, Hans W.; Hamer, C.J.A. van den

doi:10.1007/978-3-642-68269-8_161

Cited by 1 publication

(2 citation statements)

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“…were done in Scinti Verse II (Fisher) using a TriCarb 46 C scintillation counting system. Results of 14 C analyses, which represents the 3,5-DIP(carboxy-14 C)S ligand are plotted as 14 A computerized pharmacokinetic simulation program, written in Fortran-90 and executed with a desktop computer, was developed for the pharmacokinetic simulation of CuPenicillamine tissue distributions and has been described and validated (Table 1) as reported elsewhere [10,11]. Flow charts are provided in these publications.…”

Section: Methodsmentioning

confidence: 99%

“…Tissue 67 Cu without the 14 concentrations at 0.5 h. Further, the 3,5-DIP(carboxy-14 C)S ligand underwent ligand exchange and excretion and could no longer be measured in blood, kidney, intestine, lung, thymus, spleen, and brain after 24 h. However, 3,5-DIP(carboxy-14 C)S was measured in liver, femur, and muscle throughout the 5-day duration of this study. Plotted data shown in Fig.…”

Section: Simulated Rate Constants K 1 (H -1 ) For 67 Cu Without or mentioning

confidence: 99%

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Pharmacokinetic Distribution of 67Cu(II)2[3,5-Diisopropyl(Carboxy- 14C)Salicylate]4 Among Murine Tissues

Blincoe¹,

Chidambaram²,

Salari³

et al. 2004

CMC

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Non-toxic doses of tetrakis-mu-3,5-diisopropylsalicylatodicopper(II) [Cu(II)2(3,5-DIPS)4] have been found to have anti-inflammatory, analgesic, anti-ulcer, anti-colitis, anti-convulsant, anti-cancer, anti-mutagenic, anti-carcinogenic, and anti-diabetic activities and, in addition, facilitates recovery from lethal irradiation and ischemia-reperfusion injuries. The goal of this research was to determine the time-dependent tissue distribution and persistence of 67Cu and the 14C labeled salicylate ligand, carboxy-14C-3, 5-diisopropylsalicylate [3,5-DIP(carboxy-14C)S], following subcutaneous administration of a 50 micromole per kilogram of body mass dose of double labeled tetrakis-mu-3,5-diisopropyl[carboxy-14C]salicylatodiaquo [67Cu]dicopper(II) 67Cu(II)4[3,5-DIP(carboxy-14C)S]4. This compound was administered to nine groups of six 20 gram female C57BL/6 mice and blood, liver, kidney, intestine, lung, thymus, femur, muscle, spleen, and brain tissues removed and analyzed for 67Cu and 14C at 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after treatment. These data were then analyzed using a pharmacokinetic model simulation program. Both 67Cu and 14C were found in all tissues as well as urine and feces at 0.5 hour after administration. As anticipated, 67Cu entered the liver storage pool; it was conserved by the kidneys, and subsequently underwent release in maintaining 67Cu levels in all other tissues. While the presence of 67Cu correlated with the presence of the salicylate ligand, 3,5-DIP (carboxy-14C)S, early in the course of this experiment, the ligand was lost via ligand exchange and could not be measured in blood, kidney, intestine, lung, thymus, spleen, and brain after 24 hours following administration. However, 3,5-DIP(carboxy-14C)S persisted in liver, femur, and muscle throughout the 5-day period of study. It is suggested that marked lipophilicity accounts for its very rapid distribution to all tissues wherein it undergoes ligand exchange as 67Cu is incorporated into Cu-dependent enzymes and proteins and persists in tissues based upon physiological demand for Cu in meeting normal biochemical requirements.

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Section: Methodsmentioning

confidence: 99%

Section: Simulated Rate Constants K 1 (H -1 ) For 67 Cu Without or mentioning

confidence: 99%