UNCOUPLING ACTION OF 2,4-DINITROPHENOLS 2-TRIFLUOROMETHYLBENZIMIDAZOLES AND CERTAIN OTHER PESTICIDE CHEMICALS UPON MITOCHONDRIA FROM DIFFERENT SOURCES AND ITS RELATION TO TOXICITY

In order to elucidate the mode of action of representative pesticide chemicals and related substituted 2,4-dinitrophenols, 2-trifluoromethylbenzimidazoles, salicylanilides, carbonyl cyanide phenylhydrazones and certain other compounds, studies were made on their selectivity as uncouplers of respiratory-chain phosphorylation under conditions in vitro, their effects in vivo on mitochondrial enzymes and the relationship between their uncoupling potency and toxicity, using various insects and mammals. Generally, mitochondria from mouse liver are less sensitive to uncouplers than mitochondria from mouse brain or from insect tissues. Some of the uncouplers are nonselective while others are active at a much lower concentration with a particular mitochondrial source. Partial correlations are evident between the potency of the compounds for uncoupling in vitro of mitochondria from housefly thoraces, honey bee heads and thoraces, and mouse brain and liver and the toxicity to these species. Brain mitochondria and, in a few cases, liver mitochondria isolated from mice treated with the above-mentioned substances and with certain inhibitors of the electron transport chain generally are completely uncoupled or inhibited only when the dose used results in severe symptoms of poisoning. Thus, effects on mitochondrial function probably are most important in the mammalian brain from a toxicological standpoint. Five chemicals of high pesticidal activity but of widely varying chemical type did not uncouple or inhibit brain or liver mitochondria in mice with severe symptoms of poisoning and so their mode of action involves other mechanisms. © 1969.