| Specific dose-dependent damage of Lieberkühn crypts promoted by large doses of type 2 ribosome-inactivating protein nigrin b intravenous injection to mice. | |
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MedLine Citation:
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PMID: 16102565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10(5) and 5 x 10(3) times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days. Analysis of several major tissues by light microscopy did not reveal gross nigrin b-promoted changes, except in the intestines which appeared highly damaged. As a consequence of the injury, the villi and crypt structures of the small intestine disappeared, leading to profuse bleeding and death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal to mice but did trigger reversible toxic effects. In both cases, lethal and sub-lethal doses, the target of nigrin b appeared to be the highly proliferating stem cells of the intestinal crypts, which had undergone apoptotic changes. In contrast to nigrin b, the injection of 3 mug/kg of ricin kills all mice in 5 days but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub-lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320 human colon adenocarcinoma cells with an IC(50) of 3.1 x 10(-8) M and the effect was parallel to the extent of DNA fragmentation of these cells. Accordingly, despite the low general toxicity exerted by nigrin b as compared with ricin, intravenous injection of large amounts of nigrin b is able to kill mouse intestinal stem cells without threatening the lives of the animals, thereby opening a door for its use for the targeting of intestinal stem cells. |
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Authors:
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M J Gayoso; R Muñoz; Y Arias; R Villar; M A Rojo; P Jiménez; J M Ferreras; I Aranguez; T Girbés |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 207 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-16 Completed Date: 2005-09-29 Revised Date: 2008-07-12 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 138-46 Citation Subset: IM |
Affiliation:
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Departamento de Biología Celular, Histología y Farmacología, Universidad de Valladolid, 47005 Valladolid, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Cell Line, Tumor DNA Fragmentation / drug effects Dose-Response Relationship, Drug Humans Injections, Intravenous Intestine, Small / drug effects*, pathology Mice N-Glycosyl Hydrolases / toxicity* Plant Proteins / toxicity* Ribosome Inactivating Proteins, Type 2 Ricin / toxicity Stem Cells / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Plant Proteins; 0/Ribosome Inactivating Proteins, Type 2; 9009-86-3/Ricin; EC 3.2.2.-/N-Glycosyl Hydrolases |
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