Aminothiol receptors for decorporation of intravenously administered (60)Co in the rat.
This report provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic (60)Co to that observed following intravenous administration of GSH and Cys in F344 rats. Aminoacid L-histidine (His) containing no thiol functionality was tested intravenously to compare in vivo efficacy of the aminothiol (GSH, Cys) chelators with that of the aminoimidazole (His) chelator. In these studies, (60)Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24-h intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for (60)Co in the rat model, although the efficacy of treatment depends largely on the systemic availability of the chelator. The intravenous route of administration of GSH or Cys was most effective in reducing tissue (60)Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. The oral administration of liposomal GSH reduced (60)Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.
Levitskaia
Tatiana G
TG
Pacific Northwest National Laboratory, PO Box 999, MSIN P7-25, Richland, WA 99352, USA. tatiana.levitskaia@pnl.gov
Morris
James E
JE
Creim
Jeffrey A
JA
Woodstock
Angela D
AD
Luders
Teresa
T
Curry
Terry L
TL
Thrall
Karla D
KD
D000284:Administration, Oral; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage; D002614:Chelating Agents / Q000008:administration & dosage / Q000378:metabolism; D003037:Cobalt Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D003545:Cysteine / Q000008:administration & dosage* / Q000378:metabolism; D005978:Glutathione / Q000008:administration & dosage* / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism; D023481:Terrorism; D014018:Tissue Distribution
D000931:Antidotes; D002614:Chelating Agents; D003037:Cobalt Radioisotopes; D008081:Liposomes; D011956:Receptors, Cell Surface; D006639:Histidine; D005978:Glutathione; D003545:Cysteine