| Tin-protoporphyrin prevents experimental superficial siderosis in rabbits. | |
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MedLine Citation:
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PMID: 12152784 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Superficial siderosis of the human central nervous system is caused by small continuous or recurrent subarachnoid hemorrhages that lead to the destructive deposition of hemosiderin. The excessive tissue iron derives from heme that is oxidized in a rate-limiting step by the enzyme heme oxygenase (HO), and especially the inducible form, HO-1. We postulated that competitive inhibition of HO by tin-protoporphyrin IX (SnPP) could prevent experimental superficial siderosis. Since synthetic metalloporphyrins do not cross the blood-brain barrier, SnPP was delivered directly into the cisterna magna. Rabbits received weekly intracisternal injections of washed autologous red blood cells (RBC) over a period of 1 to 16 wk. In companion experiments, SnPP was added to the suspension of RBC, or SnPP was injected without RBC. All injections caused increased HO-1 immunoreactivity in the Bergmann glia of the cerebellar cortex and in superficial astrocytes of the piriform cortex. The injections of RBC or RBC with added SnPP also generated a vigorous microglial response. The metalloporphyrin entered the tissue in inhibitory amounts and greatly reduced the accumulation of histochemically detectable iron. It did not alter the microglial response. The observations allowed the conclusion that SnPP suppressed heme oxidation but did not affect other steps in the pathogenesis of superficial siderosis. |
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Authors:
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Arnulf H Koeppen; Andrew C Dickson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of neuropathology and experimental neurology Volume: 61 ISSN: 0022-3069 ISO Abbreviation: J. Neuropathol. Exp. Neurol. Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-08-02 Completed Date: 2002-08-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985192R Medline TA: J Neuropathol Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 689-701 Citation Subset: IM |
Affiliation:
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Neurology Service, VA Medical Center, Albany, New York 12208, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / metabolism Cerebellar Cortex / enzymology Enzyme Inhibitors / pharmacokinetics, pharmacology* Ferritins / metabolism Heme Oxygenase (Decyclizing) / metabolism Iron / metabolism Male Metalloporphyrins / pharmacokinetics, pharmacology* Protoporphyrins / pharmacokinetics, pharmacology* Rabbits Siderosis / enzymology, prevention & control* Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Metalloporphyrins; 0/Protoporphyrins; 14325-05-4/tin protoporphyrin IX; 7439-89-6/Iron; 9007-73-2/Ferritins; EC 1.14.99.3/Heme Oxygenase (Decyclizing) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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