THE PYRETHROIDS PERMETHRIN AND CYHALOTHRIN ARE POTENT INHIBITORS OF THE MITOCHONDRIAL COMPLEX-I

The synthetic pyrethroid derivatives permethrin and cyhalothrin are wi dely used insecticides that are considered to be relatively nontoxic t o higher animals. However, a variety of toxic effects on mammals have been reported. We investigated the effect of these drugs on energy cou pling by mitochondria and on the activity of the individual respirator y complexes. Using isolated rat liver mitochondria, a concentration-de pendent inhibition of glutamate and succinate sustained state 3 respir ation was found for both compounds in the micromolar range. The effect of pyrethroids on the activities of the complexes I to V were assesse d individually in submitochondrial particles (complex I) and in freeze -thawed mitochondria (complexes Il-V). Complex I (EC 1.6.5.3) was foun d to be the most sensitive link within the electron transport chain. H alf-maximal inhibition was observed at 0.73 mu M permethrin and 0.57 m u M cyhalothrin, respectively, and exhibited sigmoidal inhibition kine tics. Complexes II, III, IV and V (EC 1.3.5.1, 1.10.2.2, 1.9.3.1, 3.6. 1.34) were not significantly inhibited by up to 50 mu M of these drugs . Thus, our results reveal a mode of action of synthetic pyrethroid in secticides not previously reported.