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Formate, the Toxic Metabolite of Methanol, in Cultured Ocular Cells

Authors :
Michele M. Henry
Janice M. Burke
Janis T. Eells
Christine M. B. Skumatz
Jaime L Treichel
Source :
NeuroToxicology. 24:825-834
Publication Year :
2003
Publisher :
Elsevier BV, 2003.

Abstract

Methanol has neurotoxic actions on the human retina due to its metabolite, formic acid, which is a mitochondrial toxin. In methanol poisoned animals, morphologic changes were seen both in retinal photoreceptors and in cells of the underlying retinal pigment epithelium (RPE). Here the effects of formate exposure on the two retinal cell types were analyzed in more detail in vitro using photoreceptor (661W) and RPE (ARPE-19) cell lines. Cells were exposed for time courses from minutes to days to sodium formate at pH 7.4 or to formic acid at pH 6.8, to simulate the metabolic acidosis that accompanies methanol poisoning. Formate accumulation, cellular ATP, cytotoxicity (lactate dehydrogenase (LDH) release) and cell phenotype were analyzed. Formate accumulated with a similar biphasic pattern in both cell types, and to similar levels whether delivered as sodium formate or as formic acid. ATP changes with sodium formate treatment differed between cell types with only 661W cells showing a rapid (within minutes), transient ATP increase. The subsequent ATP decrease was earlier in 661W cells (6 h) than the ATP decrease in ARPE-19 cells (24 h), and although both cell types showed evidence of cytotoxicity, the effects were greater for 661W cells. Both cell types showed enhanced morphologic and biochemical changes with formic acid treatment including earlier and/or greater effects on ATP depletion and cytotoxicity; again effects were more pronounced in 661W cells. Formate therefore is toxic for both cell lines, with 661W cells exhibiting greater sensitivity. Medium pH also appears to play a significant role in formate toxicity in vitro.

Details

ISSN :
0161813X
Volume :
24
Database :
OpenAIRE
Journal :
NeuroToxicology
Accession number :
edsair.doi.dedup.....379ca8934c3ba32ec717ff591a394ec8
Full Text :
https://doi.org/10.1016/s0161-813x(03)00059-7