دورية أكاديمية
Tissue distribution of zinc-mesoporphyrin in rats: relationship to inhibition of heme oxygenase.
| العنوان: | Tissue distribution of zinc-mesoporphyrin in rats: relationship to inhibition of heme oxygenase. |
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| المؤلفون: | Russo SM; Center for Study of Disorders of Iron and Porphyrin Metabolism, University of Massachusetts Medical Center, Worcester., Pepe JA, Donohue S, Cable EE, Lambrecht RW, Bonkovsky HL |
| المصدر: | The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 1995 Feb; Vol. 272 (2), pp. 766-74. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0376362 Publication Model: Print Cited Medium: Print ISSN: 0022-3565 (Print) Linking ISSN: 00223565 NLM ISO Abbreviation: J Pharmacol Exp Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Bethesda, MD : American Society for Pharmacology and Experimental Therapeutics Original Publication: Baltimore : Williams & Wilkins |
| مواضيع طبية MeSH: | Heme Oxygenase (Decyclizing)/*antagonists & inhibitors , Metalloporphyrins/*pharmacokinetics, Animals ; Male ; Metalloporphyrins/administration & dosage ; Metalloporphyrins/pharmacology ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution |
| مستخلص: | Metalloporphyrins, including heme and others that inhibit heme oxygenase, are agents with expanding therapeutic potential. Recent results from our laboratory showed that a combination of heme and zinc-mesoporphyrin was remarkably effective in ameliorating biochemical features of acute porphyria. The aim of this study was to assess plasma clearance, tissue distribution and persistence, stability, toxicology and metabolic effects of zinc-mesoporphyrin, after its i.v. administration to rats. After administration of 15 mumol/kg b.wt. of zinc-mesoporphyrin (bound to serum albumin in a 1:1 molar ratio) the metalloporphyrin was rapidly cleared from plasma (half-life 3.6 h) with uptake primarily into liver and spleen, considerably less into the kidney and none detectable into the heart or brain. Hepatic heme oxygenase activity was undetectable for 4 days and less than 50% of control 1 week later. Inhibition of splenic heme oxygenase activity was also substantial but less marked than in the liver. No mortality was observed in any of the treated animals, and there was no detectable effect on gross or microscopic appearance of the liver, spleen, kidneys, heart, lungs or brain. Blood counts and chemistries remained within normal limits. We conclude that single doses of ZnMP-serum albumin are nontoxic, rapidly cleared from the plasma and persist primarily in the liver and spleen where heme oxygenase is inhibited for prolonged periods. |
| معلومات مُعتمدة: | 1P41 RR06009 United States RR NCRR NIH HHS; DK 38825 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Metalloporphyrins) 99LY10G7K9 (zinc mesoporphyrin) EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) |
| تواريخ الأحداث: | Date Created: 19950201 Date Completed: 19950315 Latest Revision: 20171116 |
| رمز التحديث: | 20240628 |
| PMID: | 7853192 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0022-3565 |
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