Immunocytochemical localization of desferrioxamine in the kidney, liver and brain of the developing and adult mouse: implications for drug processing and therapeutic mechanisms.
The iron chelator, desferrioxamine, has been shown to interfere with hydroxyl radical formation, which mediates tissue damage in several disease states. In this study, young and adult mice were given intraperitoneal injections of desferrioxamine and sacrificed after 1, 24 or 72 hr, and adult rats were given intraventricular injections and sacrificed after 24 or 72 hr. Immunohistochemical experiments, that utilized an anti-desferrioxamine antiserum, were performed to localize the cellular distribution of the drug in the kidney, liver and brain. In the kidney, the findings were as follows: 1) at 0 days, there was heterogeneous distribution of desferrioxamine, which suggests that there are functional differences between nephrons in the immature kidney; 2) with increasing age, the degree of staining decreased, which suggests that the efficiency of renal clearance of desferrioxamine increases with maturity; 3) punctate staining was superimposed onto diffuse staining, which suggests that the drug can get taken up in pinocytotic vesicles during tubular reabsorption; and 4) staining was present at 72 hr, which suggests a prolonged clearance period. In the liver, there was an absence of staining at 24 and 72 hr and only diffuse staining at 1 hr, which suggests a rapid processing of the drug by the liver. In the normal mouse brain, the drug was found localized to the choroid plexus and ependymal cells at all ages, and the staining decreased with increasing time following injection. These results indicate that there are differences in the way that desferrioxamine is processed by cells in different tissues and indicate possible therapeutic mechanisms.
Dept. of Physiology, University of Kansas Medical Center, Kansas City 66160.
S
S
Dang
C A
CA
Rasmussen
S M
SM
LeVine
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003676:Deferoxamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007106:Immune Sera; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D051381:Rats; D014018:Tissue Distribution
D007106:Immune Sera; D003676:Deferoxamine