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Uncoupling of oxidative phosphorylation in rat liver mitochondria by chloroethanols.

Authors
Bhat-HK; Ansari-GK
Source
Toxicol Lett 1991 Dec; 59(1-3):203-211
NIOSHTIC No.
00204741
Abstract
The effects of 2-chloroethanol (107073) (CE), 2,2-dichloroethanol (598389) (DCE) and 2,2,2-trichloroethanol (115208) (TCE) on the stimulation of mitochondrial respiration were compared, and a structure activity relationship was explored. Rat liver mitochondria were prepared from 2 month old male Sprague-Dawley- rats. With succinate as the respiratory substrate and using chloroethanols at 150 nanomolar, CE stimulated respiration by 28.2% and DCE by 202% while TCE inhibited mitochondrial respiration by more than 95%. The effect of change in the concentration of chloroethanols on mitochondrial respiration was also examined. CE showed maximum stimulation at 600 millimolar (mM), DCE at 150mM, and TCE at 30mM, 313%. Respiratory stimulation was not dependent upon mitochondrial protein concentration. Chloroethanols inhibited mitochondrial respiration when glutamate/malate was used as the respiratory substrate. Estimation of ATP showed that chloroethanols inhibited the synthesis of ATP. These findings indicated that chloroethanols stimulate mitochondrial respiration by uncoupling oxidative phosphorylation and that the uncoupling potency is proportional to the extent of chlorination at the beta position of haloethanol.
Keywords
NIOSH-Publication; NIOSH-Grant; Grants-other; Chlorinated-hydrocarbons; Alcohols; Cytotoxic-effects; Laboratory-animals; In-vitro-studies; Liver-microsomes; Author Keywords: Chloroethanols; Uncoupling of oxidative phosphorylation; Liver mitochondria
Contact
Human Biol Chem and Genetics University of Texas Med BR Dept of Human Biol Chem&gene Galveston, Tex 77550-2774
CODEN
TOLED5
CAS No.
107-07-3; 598-38-9; 115-20-8
Publication Date
19911201
Document Type
Journal Article
Funding Amount
721590.00
Funding Type
Grant
Fiscal Year
1992
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-02149
Issue of Publication
1-3
ISSN
0378-4274
Priority Area
Other Occupational Concerns; Grants-other
Source Name
Toxicology Letters
State
TX
Performing Organization
University of Texas Medical Branch, Galveston, Texas
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