Investigation of chitosan for decorporation of 60Co in the rat.
With the increased threat of terrorist release of radioactive materials, there is a need for non-toxic decorporation agents to treat internal contamination with radionuclides. In this study, low molecular weight chitosan was evaluated for decorporation of radioactive cobalt (60Co). The affinity of chitosan for Co(II) was tested in vitro using spectrophotometric and potentiometric titration techniques. For in vivo studies, the effect of chitosan on ingested 60Co was evaluated using F344 rats administered a single dose followed by oral chitosan. Chitosan was also evaluated for systemic decorporation of 60Co following intravenous injection with repeated chitosan administration over 5 d. Control animals received 60Co without chelation treatment. Excreta and tissues were collected for analysis using gamma-counting techniques. Results from in vitro experiments confirmed the binding of Co(II) to chitosan, with the postulated formation of a mixed cobalt-chitosan-hydroxide complex species; a stability constant was calculated for this complex. For in vivo studies, oral administration of chitosan significantly reduced systemic absorption of orally administered 60Co as evidenced by an increase in fecal elimination and decrease in urinary elimination. However, oral administration of chitosan lactate slightly decreased fecal excretion of 60Co. Further, oral administration of chitosan significantly reduced 60Co levels in kidney, liver, and skeleton compared to control animals receiving 60Co alone. By the i.v. route, chitosan slightly reduced levels of 60Co in tissues compared to controls, although statistically significant reductions were only observed for blood and kidney. Overall, this commercially available chitosan oligosaccharide exhibited promising potential; further studies are warranted to evaluate the optimal dosing regimen and chemical modifications to increase effectiveness.
Levitskaia
Tatiana G
TG
Pacific Northwest National Laboratory, PO Box 999, MSIN P7-22, Richland, WA 99352, USA. tatiana.levitskaia@pnl.gov
Creim
Jeffrey A
JA
Curry
Terry L
TL
Luders
Teresa
T
Morris
James E
JE
Sinkov
Sergei I
SI
Woodstock
Angela D
AD
Thrall
Karla D
KD
D000284:Administration, Oral; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002614:Chelating Agents / Q000008:administration & dosage*; D048271:Chitosan / Q000008:administration & dosage*; D003037:Cobalt Radioisotopes / Q000493:pharmacokinetics*; D005243:Feces; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002614:Chelating Agents; D003037:Cobalt Radioisotopes; D048271:Chitosan