抗炎症剤の赤血球膜安定化作用(第1報) : H₂O₂によるイヌ赤血球の溶血現象とLipid Peroxidationにおよぼす影響

抄録

A simple in vitro method for screening of anti-inflammatory drugs is proposed on the basis of biochemical changes which would occur uniquely in inflamed tissues. Hemolysis and lipid peroxidation were induced in 5% canine erythrocyte (RBC) suspension when incubated with 0.3% hydrogen peroxide at 37°. Lipid peroxides were formed more rapidly after the incubation, and inhibited at lower concentration of drugs than did hemolysis. Inhibitory effect of both flufenamic acid and phenylbutazone on lipid peroxide formation was not changed by preincubation with either RBC or H₂O₂, but a complete loss of the drug activity was observed when the preincubated RBC was washed before the addition of H₂O₂. Flufenamic and mefenamic acids inhibited peroxide formation in proportion to their increasing concentrations while on hemolysis the drugs, especially the latter, showed an enhancing effect at high concentrations. Potency of various anti-inflammatory drugs was compared at a fixed concentration (final, 3.75×10^-4 M). Flufenamic and mefenamic acids, aminopyrine, and betamethasone disodium phosphate caused a marked inhibitory effect on both hemolysis and lipid peroxidation. The inhibition with phenylbutazone, oxyphenbutazone, and chloroquine was found to be relatively large in peroxidation but weak in hemolysis. Aspirin showed a marked protection of hemolysis but did not modify the production of lipid peroxides. Salicylate and prednisolone sodium hemisuccinate were inactive in both instances. A possible mechanism of drug action against hemolysis and lipid peroxidation induced by hydrogen peroxide is discussed.