Document Detail


Methotrexate induces cell swelling and necrosis in renal tubular cells.
MedLine Citation:
PMID:  16025437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marika Grönroos; Ming Chen; Timo Jahnukainen; Arrigo Capitanio; Roman I Aizman; Gianni Celsi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric blood & cancer     Volume:  46     ISSN:  1545-5009     ISO Abbreviation:  Pediatr Blood Cancer     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-03-13     Completed Date:  2006-05-04     Revised Date:  2009-01-12    
Medline Journal Info:
Nlm Unique ID:  101186624     Medline TA:  Pediatr Blood Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  624-9     Citation Subset:  IM    
Affiliation:
Department of Paediatrics, Turku University Central Hospital, Turku, Finland. marika.gronroos@utu.fi
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MeSH Terms
Descriptor/Qualifier:
Amiloride / 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:
0/Antimetabolites, Antineoplastic; 0/Sodium Channel Blockers; 2609-46-3/Amiloride; 59-05-2/Methotrexate
Comments/Corrections
Comment In:
Pediatr Blood Cancer. 2007 Aug;49(2):216;author reply 219   [PMID:  16786587 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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