DDT‐membrane interactions studied with two fluorescent probes

Abstract

The effects of DDT (0‐100 μM) in pure phospholipid and phospholipid/cholesterol bilayers were investigated by fluorescence polarization of 1,6‐diphenyl‐1,3,5‐hexatriene (DPH), a probe located in the bilayer interior, and by excimer to monomer fluorescence intensity ratio (I′/I) of 1,3‐di(l‐pyrenyl)propane (Py(3)Py), a probe sitting closer to the polar region. In the gel phase of dimyristoylphosphatidylcholine (DMPC) bilayers, DDT induces concentration‐dependent fluidizing effects into the hydrophobic membrane regions, but no effects are observed in the outer regions of the membrane, as evaluated by DPH and Py(3)Py, respectively. Furthermore, in the fluid phase of DMPC and for DDT concentrations higher than 10 μM, I′/I of Py(3)Py decreases, reflecting an order increase of the probe environment and DPH fails to detect any apparent effect. Similar effects were observed in other pure lipid bilayers, namely dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC). Unlike DPH, Py(3)Py is very sensitive to DPPC and DSPC pre‐transitions which are not abolished by 50 μM DDT. This DDT concentration inhibits to some extent the cholesterol‐induced ordering in DMPC bilayers and high cholesterol concentrations (⩾ 30 mol%) do not prevent insecticide interaction, as evaluated by DPH. On the other hand, the effects of DDT reported by Py(3)Py depend on temperature and cholesterol content of DMPC bilayers. Thus, for cholesterol levels ranging from 10 to 50 mol% and for temperatures below the phase transition temperature of DMPC, Py(3)Py fails to detect any significant effect. Nevertheless, above the phase transition temperature of DMPC, Py(3)Py detects either ordering effects of DDT at low cholesterol contents (< 20 mol%) or fluidizing DDT effects at high cholesterol levels (> 20 mol%).

Membrane-Water Partitioning of Polychlorinated Biphenyls in Small Unilamellar Vesicles of Four Saturated Phosphatidylcholines

“…At the experimental temperature of 37 "C, DPPC is in the ripple phase (see Table 1) and shows the highest membrane-water partition coefficients in our experiments, probably due to larger holes that are present in the bilayer. In the work of Antunes et al, it can also be seen that the partitioning of DDT into DMPC vesicles is the highest at 24 "C where DMPC is in the ripple phase (11). At any definite temperature, phospholipids have a particular fluidity dependent on their phase main transition temperature.…”

“…It is believed that general anesthetic toxicological effects of hydrophobic compounds are the result of compound-membrane interactions (9,10). The biochemical aspects of these interactions are poorly understood, but it is suggested that hydrophobics inserted in the membrane can alter the membrane fluidity and so interfere with biological functions of the membrane (11,12).…”

Kinetics and conductivity parameters of uptake and transport of polychlorinated biphenyls in the Caco‐2 intestinal cell line model

“…Chem. 17,1998 W.J. Dulfer et al The conductivity of the Caco-2 cell monolayer to PCB transport from the apical membrane to the basolateral compartment can be calculated following Equation 4, D trans ϭ N trans / (f ap Ϫ f baso ), where (f ap Ϫ f baso ) denotes the difference in fugacity between the apical and the basolateral compartment.…”

“…Rahman and Barrowman [15] showed that for the uptake of PAHs with very low aqueous solubilities, the unstirred water layer forms the major resistance, and the bioavailability of these chemicals was enhanced significantly by incorporation in bile salt micelles. High affinities of various chlorinated hydrocarbons and the hydrophobic pesticide dichlorodiphenyltrichloroethane (DDT) to membrane vesicles were observed by Omann and Lackowicz and by Antunes‐Madeira et al, respectively [16,17]. The high solubilization capacity of lipoproteins for hydrophobic contaminants is supported by the observation that lipoproteins form the major binding site in hepatic cytosol and transport vehicle in the plasma for hydrophobic xenobiotics [18–20].…”

“…ities of various chlorinated hydrocarbons and the hydrophobic pesticide dichlorodiphenyltrichloroethane (DDT) to membrane vesicles were observed by Omann and Lackowicz and by Antunes-Madeira et al, respectively [16,17]. The high solubilization capacity of lipoproteins for hydrophobic contaminants is supported by the observation that lipoproteins form the major binding site in hepatic cytosol and transport vehicle in the plasma for hydrophobic xenobiotics [18][19][20].…”