Influence of pyrethroids and piperonyl butoxide on histamine release from isolated rat mast cells

Abstract

Pyrethroids are insecticides with low acute toxicity in mammals but their world-wide use for domestic and occupational purposes has caused concern about the risks of long-term exposure. The mammalian toxicity of pyrethroids is related to disturbances of membrane function in neuronal tissues whereas their influence on nonneuronal tissues is poorly understood. Recently, selected pyrethroids were shown to affect the function of rat synaptosomal and leukocyte membranes similarly. The present investigation explores to what extent their influence on the function of intact cells, i. e. isolated rat mast cells, correlates with these membrane interactions. Permethrin and the more water soluble esbiol (S-bioallethrin), both type I pyrethroids, and cyfluthrin, type II, used alone and together with the enhancing substance piperonyl butoxide (PBO) at concentration ratios of 1:5 and 1:10, were tested for influence on histamine release induced by compound 48/80 without and with calcium. Permethrin (5-10 microM) caused a 10-25 % inhibition of the histamine release in the absence of calcium but did not affect the response with calcium present and had no interaction with PBO. Esbiol (10 microM) was an effective inhibitor on its own, with 70 and 45% inhibition in the absence and presence of calcium, respectively, and caused virtually complete inhibition in a synergistic interaction with PBO. The effect of esbiol could partly be ascribed to inhibition of oxidative energy production. Cyfluthrin was inactive at concentrations up to 10 microM. PBO alone (50 microM) caused some inhibition, in particular in the absence of calcium (ca. 25 %). The results relating to mast cell histamine release reveal both similarities and differences with the influence of the pyrethroids on cell membrane activities. They indicate that not solely membrane interactions but also additional or alternative targets are involved in the effects of pyrethroids on mammalian tissues. Moreover, the pronounced effects of a brief cell exposure suggest that long-term exposure can be hazardous.