Evaluation of antiepileptic drug effect on membrane fluidity.
Many drugs and chemicals have been shown to induce modifications of the physicochemical properties of cellular membranes. In this study we investigated the changes in fluidity of erythrocyte membrane from epileptic patients under different pharmacological treatments, with respect to healthy controls, by using trimethylammonium-1,6-diphenyl-1,3,5-hexatriene (TMA-DPH) fluorescence polarization. The increase in TMA-DPH fluorescence polarization values observed in epileptic patients indicated a decrease in membrane fluidity. Since the analysis of erythrocyte membrane composition did not reveal significant differences between the two groups studied, a correlation with membrane lipoperoxide content was tried, as different drugs and chemicals elicit in vivo alterations resulting in peroxidation of membrane lipids. Therefore the presence of peroxidation products in the blood and the possible correlation with membrane lipoperoxide were studied. Although a direct causal linkage cannot be proved we can hypothesize that exogenous compounds such as antiepileptic drugs could modify membrane fluidity by increasing membrane lipid peroxidation. Moreover the increase of peroxidative products in the blood could indicate that the peroxidative damage might propagate through the formation of new free radical species. The possibility of using erythrocyte membrane as a model system to analyze antiepileptic drug side effects is advanced.
Institute of Biochemistry, Faculty of Medicine, University of Ancona, Italy.
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Tangorra
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Curatola
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Bertoli
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D002648:Child; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism
D000927:Anticonvulsants; D005456:Fluorescent Dyes; D005609:Free Radicals; D008563:Membrane Lipids; D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene