Differential effects of in vitro peroxidation on peripheral- and central-type benzodiazepine receptors. Protection by diverse antioxidants.
The influence of various concentrations of ferrous iron and ascorbate on in vitro peroxidation and drug binding of diverse membrane preparations (cerebral cortex and liver) was studied. Peroxidation was not simply dose-related to ascorbate and ferrous iron, but a complex relationship between iron and ascorbate when added in association was established. Under our conditions 0.01 mM Fe2+ and 0.5 mM ascorbate was the most peroxidative combination for cerebral and liver membranes. Under the same conditions, cerebral membranes were more peroxidated than liver membranes. Considering the consequences of drug binding, peripheral-type benzodiazepine receptors (PBRs) of liver were more affected by peroxidative events than central-type benzodiazepine receptors (CBRs) of the cerebral cortex. The degree of binding disturbance was generally inversely correlated to the degree of peroxidation and this was more significant for liver PBRs than for cerebral CBRs. The liver membrane model was retained for testing in vitro protection by diverse putative antioxidants. Under our conditions desferrioxamine, ethylene diamine tetra acetate (EDTA), trolox, and rutin were good protective antioxidants, whereas phenyl-butyl-nitrone (PBN) and tocopherol were not effective.
Courtiere
A
A
Institut de Médecine Navale du Service de Santé des Armées, Toulon Naval, France.
Molard
F
F
Reybaud
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001570:Benzodiazepinones / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008315:Malondialdehyde / Q000032:analysis; D011963:Receptors, GABA-A / Q000378:metabolism*; D012431:Rutin / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001570:Benzodiazepinones; D002839:Chromans; D005296:Ferrous Compounds; D000960:Hypolipidemic Agents; D011963:Receptors, GABA-A; D014810:Vitamin E; C028513:4'-chlorodiazepam; D008315:Malondialdehyde; D012431:Rutin; D005445:Flunitrazepam; D004492:Edetic Acid; D003676:Deferoxamine; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid