Perturbation of Rat Heart Plasma Membrane Fluidity Due to Metabolites of Permethrin Insecticide

Abstract

Due to increased global use, acute and chronic exposures to pyrethroid insecticides in humans are of clinical concern. Pyrethroids have a primary mode of action that involves interference with the sodium and calcium channels in excitable cells, which may include cardiac myocytes. Here, we investigated the possible cardiac toxicity of permethrin metabolites (METP), 3-phenoxy-benzyl alcohol (3PBA), 3-phenoxy-benzaldehyde (3PBALD), and 3-phenoxybenzoic acid (3PBACID). Plasma membrane fluidity, polarity, lipid, and protein oxidation were studied in isolated rat heart cells. Laurdan was chosen as probe to detect the lateral mobility and polarity of its environment and thus water penetration into the hydrophobic part of the bilayer, while 1,6-diphenyl-1,3,5-hexatriene permits to measure changes in fluidity in the inner part of the bilayer. Results show that METP can change membrane fluidity at different depths of the bilayer according to their partition coefficient. Consequently, 3PBA, at all concentration used, decreases membrane fluidity and polarity in the hydrophilic-hydrophobic region of the bilayer, and similar effect was observed with 20μM 3PBALD or 10 or 20μM 3 PBACID. Membrane dynamics in the hydrophobic core resulted decreased by 3PBALD, while it was increased by 20μM 3PBACID. All METP increase protein and lipid oxidation, and the peroxidative lipid damage decreases with the type of METP produced during the transformation pathway from parent compound to 3PBACID. Consequently, 3PBA induced the highest lipid peroxidation, while 3PBACID was the stronger inducer of protein damage.