Non-cholinergic toxicity of organophosphates in mammals: interaction of ethaphos with mitochondrial functions.
The effect of the organophosphorus insecticide O-ethyl-S-propyl-2,4-dichlorophenylphosphorothioate (ethaphos) on mitochondrial functions was studied. It was shown that ethaphos interacts with mitchondrial oxidative metabolism and inhibits oxidation of succinate, alpha-glycerophosphate and pyruvate+malate at concentrations of 100, 75 and 50 micrograms mg-1 mitochondrial protein, respectively. Mitochondria treated with ethaphos show no changes in the inner membrane permeability and activity of cytochromes of the respiratory chain. Ethaphos has no inhibitory effect on the activity of mitochondrial ATPase. Addition of the electron donor pair (ascorbic acid + N,N,N',N'-tetramethyl-p-phenylenediamine) to ethaphostreated mitochondria restored the respiration and membrane potential. The membrane potential also can be re-established in poisoned mitochondria by the addition of exogenous ATP. Based on the data obtained we show that mitochondrial dysfunctions induced by ethaphos can be partially eliminated and mitochondrial functions can be restored using artificial electron donors and/or through increasing the cytosolic ATP level.
Holmuhamedov
E L
EL
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.
Kholmoukhamedova
G L
GL
Baimuradov
T B
TB
D000255:Adenosine Triphosphate / Q000627:therapeutic use; D000818:Animals; D001205:Ascorbic Acid / Q000627:therapeutic use; D018680:Cholinergic Antagonists / Q000633:toxicity*; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D013772:Tetramethylphenylenediamine / Q000627:therapeutic use
D018680:Cholinergic Antagonists; D007306:Insecticides; D009946:Organothiophosphorus Compounds; C035962:etafos; D000255:Adenosine Triphosphate; D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid