Document Detail

Oxalate toxicity in LLC-PK1 cells: role of free radicals.
MedLine Citation:
PMID:  8821825     Owner:  NLM     Status:  MEDLINE    
Oxalate, the most common constituent of kidney stones, is an end product of metabolism that is excreted by the kidney. During excretion, oxalate is transported by a variety of transport systems and accumulates in renal tubular cells. This process has been considered benign; however, recent studies on LLC-PK1 cells suggested that high concentrations of oxalate are toxic, inducing morphological alterations, increases in membrane permeability to vital dyes and loss of cells from the monolayer cultures. The present studies examined the basis for oxalate toxicity, focusing on the possibility that oxalate exposure might increase the production/availability of free radicals in LLC-PK1 cells. Free radical production was monitored in two ways, by monitoring the reduction of nitroblue tetrazolium to a blue reaction product and by following the conversion of dihydrorhodamine 123 (DHR) to its fluorescent derivative, rhodamine 123. Such studies demonstrated that oxalate induces a concentration-dependent increase in dye conversion by a process that is sensitive to free radical scavengers. Specifically, addition of catalase or superoxide dismutase blocked the oxalate-induced changes in dye fluorescence/absorbance. Addition of these free radical scavengers also prevented the oxalate-induced loss of membrane integrity in LLC-PK1 cells. Thus it seems likely that free radicals are responsible for oxalate toxicity. The levels of oxalate that induced toxicity in LLC-PK1 cells (350 microM) was only slightly higher than would be expected to occur in the renal cortex. These considerations suggest that hyperoxaluria may contribute to the progression of renal injury in several forms of renal disease.
C Scheid; H Koul; W A Hill; J Luber-Narod; L Kennington; T Honeyman; J Jonassen; M Menon
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Kidney international     Volume:  49     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-11-15     Completed Date:  1996-11-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  413-9     Citation Subset:  IM    
Department of Physiology, University of Massachusetts Medical School, Worcester, USA.
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MeSH Terms
Free Radicals / metabolism
LLC-PK1 Cells / drug effects*,  metabolism
Nitroblue Tetrazolium
Oxalates / toxicity*
Oxidative Stress
Grant Support
Reg. No./Substance:
0/Free Radicals; 0/Oxalates; 0/Rhodamines; 109244-58-8/dihydrorhodamine 123; 298-83-9/Nitroblue Tetrazolium

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