Efficacy and toxicity of N,N',N",N"'-tetra(2,3,4-trihydroxybenzoyl)-spermine for decorporation of 239Pu from mice.
Male SAS/4 mice were injected i.v. with 6.6 kBq 239Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 mumol kg-1 or repeated (three or four) daily injections of 30 mumol kg-1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DTPA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 mumol kg-1 or at 2-13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 mumol kg-1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 mumol kg-1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.
Szot
Z
Z
Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
Rochalska
M
M
Chomiczewski
K
K
Chimiak
A
A
Przychodzeń
W
W
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D004369:Pentetic Acid / Q000494:pharmacology; D011005:Plutonium / Q000493:pharmacokinetics*; D013095:Spermidine / Q000031:analogs & derivatives / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D002614:Chelating Agents; C058259:N,N',N'',N'''-tetra(2,3,4-trihydroxybenzoyl)spermine; D013096:Spermine; D011005:Plutonium; C034834:LICAM-C; D004369:Pentetic Acid; D013095:Spermidine