| Methotrexate induces cell swelling and necrosis in renal tubular cells. | |
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MedLine Citation:
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PMID: 16025437 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The present study was carried out to investigate if methotrexate (MTX) has a direct lethal effect in renal tubular cells, and if so, to further clarify the mechanisms of cell death. MATERIALS AND METHODS: Renal tubular cells (LLC-PK(1) cells) were incubated with MTX (0.01 microM, 0.1 microM, and 1 microM), either alone or in combination with 0.1 microM amiloride (Na(+)/H(+) antiporter inhibitor) or 1 microM carbachol (M-cholinergic agonist). Cell viability was then determined by means of trypan blue (TB) exclusion tests and MTT assays. RESULTS: After 4 hr incubation with 0.1 microM MTX the number of viable cells was decreased by 18% in comparison with control cells, and the proportion of dead cells was increased by 38%. Cell death induced by MTX was time-dependent and did not show apoptotic features. On the contrary, cell swelling was discovered. This cell death was prevented by co-incubating the cells with amiloride or carbachol. CONCLUSIONS: MTX induces cell swelling and cell death in renal tubular LLC-PK(1) cells. The tubular cell death induced by MTX is time-dependent. Cell death can be prevented by co-incubating with amiloride, thus indicating that the Na(+)/H(+) antiporter and possibly other volume regulatory factors in renal tubular cells are involved in MTX-induced renal failure. |
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Authors:
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Marika Grönroos; Ming Chen; Timo Jahnukainen; Arrigo Capitanio; Roman I Aizman; Gianni Celsi |
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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: Pediatric blood & cancer Volume: 46 ISSN: 1545-5009 ISO Abbreviation: Pediatr Blood Cancer Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-03-13 Completed Date: 2006-05-04 Revised Date: 2009-01-12 |
Medline Journal Info:
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Nlm Unique ID: 101186624 Medline TA: Pediatr Blood Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 624-9 Citation Subset: IM |
Affiliation:
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Department of Paediatrics, Turku University Central Hospital, Turku, Finland. marika.gronroos@utu.fi |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amiloride
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pharmacology Animals Antimetabolites, Antineoplastic / pharmacology* Cell Size / drug effects* Cell Survival / drug effects* Kidney Tubules, Proximal / drug effects*, pathology LLC-PK1 Cells / cytology, drug effects Methotrexate / pharmacology* Necrosis Sodium Channel Blockers / pharmacology Swine |
| Chemical | |
Reg. No./Substance:
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0/Antimetabolites, Antineoplastic; 0/Sodium Channel Blockers; 2609-46-3/Amiloride; 59-05-2/Methotrexate |
| Comments/Corrections | |
Comment In:
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Pediatr Blood Cancer. 2007 Aug;49(2):216;author reply 219
[PMID:
16786587
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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