In vitro effects of pyrethroids on rat brain and liver ATPase activities

Abstract

In vitro sensitivity of rat brain and liver ATPases to pyrethroid insecticides, belonging to three categories based on the structural configuration, was studied. Rat brain and liver p ₂ fractions were prepared by the conventional centrifugation method, and rat brain synaptosomes were prepared by Ficoll‐sucrose gradient centrifugation method. Na⁺, K⁺‐ATPase and oligomycin‐sensitive and ‐insensitive Mg²⁺‐ ATPases were determined in brain P ₂ fraction, whereas in liver P ₂ fraction only oligomycin‐sensitive and ‐insensitive Mg²⁺‐ATPase activities were determined. [ ³ H]Ouabain binding studies were carried with rat brain synaptosomes. Most of the pyrethroid compounds tested inhibited brain and liver oligomycin‐sensitive Mg ²⁺ ‐ATPases at micromolar concentrations. Type II compounds were more effective as compared to Type I compounds. Oligomycin‐insensitive Mg ²⁺ ‐ATPase was not affected by any of the compounds tested except deltamethrin, which showed significant effect on liver enzyme. Na⁺, K⁺‐ATPase of brain was less sensitive to these pyrethroids as compared to oligomycin‐sensitive Mg²⁺‐ATPase. [ ³ H]Ouabain binding to rat brain synaptosomes was not affected significantly by these pyrethroid insecticides. These results suggest that inhibition of oligomycin‐sensitive Mg ²⁺ ‐ATPase may be involved in the toxicity of pyrethroid compounds.