TOXICITY OF ORGANOPHOSPHORUS INSECTICIDES - ALTERATION OF MEMBRANE FLUIDITY

The interaction of malathion, ethylazinphos, methylparathion and parat hion with model and native membranes was investigated by fluorescence anisotropy of DPH (1,6-diphenyl-1,3,5 -hexatriene) probing the bilayer core, and by its propionic acid derivative (DPH-PA) probing the outer region of the bilayer. The insecticides broadened the transition prof ile and shift the phase transition midpoint to lower temperatures. On the other hand, they ordered the fluid phase of the lipid either in th e hydrophobic or in the outer regions of the bilayer, as detected by D PH and DPH-PA, respectively. Cholesterol modulated to a great extent t he ordering effects of the above insecticides, either in model or in n ative membranes. The compounds increased to some extent the ordering p romoted by cholesterol, but high cholesterol concentrations (greater t han or equal to 30 mol%) prevented insecticide interaction. The degree of interactions may be described by the following order of potency: m alathion << ethylazinphos less than or equal to methylparathion < para thion. This sequence correlates reasonably with the toxicity of the co mpounds to mammals. Since the fluidity of the cytoplasmic membrane is a major parameter in the control of cell homeostasis, the described ph ysical perturbations may be partially involved in the physiological ef fects promoted by these xenobiotics-effects not directly related to th eir acute cholinergic actions.