Targeting of heme oxygenase inhibitors to the spleen markedly increases their ability to diminish bilirubin production

Incorporation of heme oxygenase inhibitors into phosphatidyl choline liposomes markedly enhanced localization of these agents within the spleen as compared with the localization observed following their administration in aqueous vehicle. The increased concentration of inhibitor within splenic micros...

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Bibliographic Details
Published in:Pediatrics (Evanston) 1989-12, Vol.84 (6), p.1091-1096
Main Authors: LANDAW, S. A, DRUMMOND, G. S, KAPPAS, A
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Animals
Bilirubin - biosynthesis
Biological and medical sciences
Drug Carriers
Enzymes and enzyme inhibitors
Fundamental and applied biological sciences. Psychology
Heme Oxygenase (Decyclizing) - antagonists & inhibitors
Liposomes
Liver - analysis
Liver - enzymology
Male
Metalloporphyrins - administration & dosage
Metalloporphyrins - pharmacokinetics
Mixed Function Oxygenases - antagonists & inhibitors
Oxidoreductases
Porphyrins - administration & dosage
Protoporphyrins - administration & dosage
Protoporphyrins - pharmacokinetics
Rats
Rats, Inbred Strains
Spleen - analysis
Spleen - enzymology
Spleen - metabolism
Tissue Distribution
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Summary:Incorporation of heme oxygenase inhibitors into phosphatidyl choline liposomes markedly enhanced localization of these agents within the spleen as compared with the localization observed following their administration in aqueous vehicle. The increased concentration of inhibitor within splenic microsomes led to a near complete and sustained blockade of heme oxygenase activity and thus to a marked diminution in biliary bilirubin output. These studies suggest that heme oxygenase inhibitors administered within liposomes may so effectively block bilirubin production in the human newborn that ancillary methods for treating this important clinical problem may be reduced to a minimum.
ISSN:0031-4005
1098-4275
DOI:10.1542/peds.84.6.1091