Comparison of uncoupling activities of chlorophenoxy herbicides in rat liver mitochondria.
The effects of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), 4-chloro-2-methylphenoxyacetic acid (MCPA) and 2-(2,4,5-trichlorophenoxy)propionic acid (2,4,5-TP) on respiration and oxidative phosphorylation in rat liver mitochondria were examined in vitro. Respiration rates of glutamate, malate and succinate were investigated in the presence of each herbicide (0.1-4.0 mM). At lower concentrations, all herbicides stimulated state 4 respiration, decreased the respiratory control ratio and the ADP/O ratio. The respiration rate in state 3 and uncoupled state was unaffected. At higher concentrations all bioenergetic parameters, respiration in state 4, 3 and uncoupled state, as well as respiratory control ratio and ADP/O, were inhibited in a concentration-dependent manner. These data indicate that these herbicides alter energy metabolism in rat liver mitochondria by uncoupling of oxidative phosphorylation. 2,4,5-TP possesses the strongest uncoupling properties followed by 2,4,5-T, MCPA and 2,4-D in that order.
Zychlinski
L
L
Toxlab Research Institute, Tampa, FL 33549.
Zolnierowicz
S
S
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015084:2,4-Dichlorophenoxyacetic Acid / Q000494:pharmacology; D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid; D000244:Adenosine Diphosphate; D015085:2,4,5-Trichlorophenoxyacetic Acid; C009264:fenoprop; D008456:2-Methyl-4-chlorophenoxyacetic Acid