Abstract
Effects of ethylenediamine tetraacetic acid (EDTA) on aging-induced changes in activities of drug metabolizing enzymes were investigated. Aging of microsomes at 45° produced a reduction of lipid peroxidation while aging of 9000×g supernatant fraction at 45° resulted in a marked increase in the formation of lipid peroxides. From this finding, it was assumed that there might be heat stable stimulator of lipid peroxidation in addition to the heat labile inhibitor of lipid peroxidation which was found recently by us. EDTA completely prevented the inactivation of aniline hydroxylase and aminopyrine N-demethylase when rat liver 9000×g supernatant fraction was aged at 45°. When rat liver 9000×g supernatant fraction and microsomes were aged at 5° aerobically, activity of ethylmorphine N-demethylase was decreased and, inversely, amount of lipid peroxides formed during aging was increased. EDTA effectively inhibited the lipid peroxidation and decrease in ethylmorphine N-demethylase activity. The close relationship between lipid peroxidation and activity of ethylmorphine N-demethylase was confirmed using NADPH-generating system and ferrous ion as stimulators of lipid peroxidation.
