Comparative iron mobilizing actions of deferoxamine, 1,2-dimethyl-3-hydroxypyrid-4-one, and pyridoxal isonicotinoyl hydrazone in iron hydroxamate-loaded mice.
A comparison was made of the actions of deferoxamine (DFX), 1,2-dimethyl-3-hydroxypyrid-4-one (L1), and pyridoxal isonicotinoyl hydrazone (PINH) in mobilizing and promoting excretion of iron in mice loaded with iron-acetohydroxamic acid complex. DFX was given ip, while L1 and PINH were given po. Each was given daily for four days at 300 mg/kg/day, and total excreta were collected 24 hr after each administration. Total iron excreted over the 4-day period, expressed as micrograms/mouse, were: Controls, 26; PINH-treated, 31; DFX-treated, 162; and L1-treated, 208. Measurements of iron in selected organs 96 hr after the last administration of each compound revealed that treatment with L1 and DFX induced significant reductions of iron concentrations in kidneys (16% and 17%, respectively) and in pancreas (18% and 19%, respectively). In addition, L1 treatment led to a significant reduction in the liver iron burden (11%), an action not seen after treatment with DFX. None of the compounds reduced iron concentrations in heart, the most critical organ for toxicity of transfusional siderosis. The synthetic routes for preparation of L1 and PINH are described in detail.
Gale
G R
GR
Veterans Affairs Medical Center, Charleston, SC 29403.
Litchenberg
W H
WH
Smith
A B
AB
Singh
P K
PK
Campbell
R A
RA
Jones
M M
MM
D000818:Animals; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011728:Pyridones / Q000494:pharmacology*; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000494:pharmacology; D014018:Tissue Distribution
D006877:Hydroxamic Acids; D011728:Pyridones; D000077543:Deferiprone; D011730:Pyridoxal; C006358:acetohydroxamic acid; C021079:pyridoxal isonicotinoyl hydrazone; D007501:Iron; D003676:Deferoxamine; D007538:Isoniazid