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HERO ID
3859964
Reference Type
Journal Article
Title
Esterification prevents induction of the mitochondrial permeability transition by N-acetyl perfluorooctane sulfonamides
Author(s)
O'Brien, TM; Carlson, RM; Oliveira, PJ; Wallace, KB
Year
2006
Is Peer Reviewed?
Yes
Journal
Chemical Research in Toxicology
ISSN:
0893-228X
EISSN:
1520-5010
Publisher
AMER CHEMICAL SOC
Location
WASHINGTON
Volume
19
Issue
10
Page Numbers
1305-1312
Language
English
PMID
17040099
DOI
10.1021/tx060132r
Web of Science Id
WOS:000241232900006
URL
https://search.proquest.com/docview/68958270?accountid=171501
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Abstract
N-Alkyl perfluorooctane sulfonamides have been widely used as surfactants on fabrics and papers, fire retardants, and anticorrosion agents, among many other commercial applications. The broad use, global distribution, and environmental persistence of these compounds has generated considerable interest regarding potentially toxic effects. We have previously reported that perfluorooctanesulfonamidoacetate (FOSAA) and N-ethylperfluorooctanesulfonamidoacetate (N-EtFOSAA) induce the mitochondrial permeability transition (MPT) in vitro, resulting in cytochrome c release, inhibition of respiration, and generation of reactive oxygen species. By synthesizing the corresponding methyl esters of FOSAA and N-EtFOSAA (methyl perlfuorinated sulfonamide acetates), we tested the hypothesis that the N-acetate moiety of FOSAA and N-EtFOSAA is the functional group responsible for induction of the MPT. Swelling of freshly isolated liver mitochondria from Sprague-Dawley rats was monitored spectrophotometrically and membrane potential (DeltaPsi) was measured using a tetraphenylphosphonium-selective (TPP(+)) electrode. In the presence of calcium, 40 microM FOSAA and 7 microM N-EtFOSAA each induced mitochondrial swelling and a biphasic depolarization of membrane potential. Mitochondrial swelling and the second-phase depolarization were inhibited by cyclosporin-A or the catalyst of K(+)/H(+) exchange nigericin, whereas the first-phase depolarization was not affected by either. In contrast, the methyl esters of FOSAA and N-EtFOSAA exhibited no depolarizing or MPT inducing activity. Results of this investigation demonstrate that the carboxylic acid moiety of the N-acetates is the active functional group, which triggers the MPT by perfluorinated sulfonamides.
Keywords
Fluorocarbons; Sulfonamides; Calcium; SY7Q814VUP; Index Medicus; Permeability -- drug effects; Calcium -- chemistry; Rats, Sprague-Dawley; Esterification; Calcium -- pharmacology; Membrane Potential, Mitochondrial -- drug effects; Animals; Titrimetry; Mitochondrial Swelling -- drug effects; Molecular Structure; Sulfonamides -- chemistry; Sulfonamides -- pharmacology; Mitochondrial Membranes -- drug effects; Fluorocarbons -- chemistry
Tags
PFAS
•
Additional PFAS (formerly XAgency)
Literature Search November 2019
Other Sources
TEDX
Screened Studies
Supplemental
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
PubMed
Web of Science
Other Sources
PFAS TOX Database
Screened Studies
Excluded
Exclude (TIAB)
Not prioritized for screening
Perfluorooctane
2-(N-Ethyl-perfluorooctanesulfonamido)acetate
2-(N-Ethylperfluorooctanesulfonamido)acetic acid
•
NEtFOSAA
Literature Search
Pubmed
WOS
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In vitro/ex vivo/in silico
Other mechanistic studies
•
^Per- and Polyfluoroalkyl Substances (PFAS)
NEtFOSAA (2991-50-6)
Literature Search
Pubmed
WOS
•
PFAS 150
Literature Search Update December 2020
PubMed
WOS
Literature Search August 2019
PubMed
Web of Science
Other sources
PFAS TOX Database
Not prioritized for screening
Perfluorooctane
•
Yale PFAS Liver study
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