Interaction between nonsteroidal anti-inflammatory drugs and biological membranes—IV: Effects of nonsteroidal anti-inflammatory drugs and of various ions on the availability of sulfhydryl groups on lymphoid cells and mitochondrial membranes

Abstract

A stimulation effect of various nonsteroidal anti-inflammatory drugs (NSAID) on a sulfhyd-ryl-disulfide interchange reaction between serum protein sulfhydryl groups and 5,5'-dithiobis-(2-nitro-benzoic) acid (DTNB) has been described. We now describe a similar reaction between 65 μM DTNB and protein sulfhydryl groups in rat, rabbit and human lymphocyte membranes and rat liver mitochondria. This reaction is greatly accelerated in the presence of ten different NSAID. The stimulation of this sulfhydryl-disulfide interchange reaction appears to be dependent on drug concentration. It is also closely related to the ionic composition of the incubation medium which, by itself, according to specific cationic and anionic sequences, influences the availability of sulfhydryl groups on membranes. The reaction of 0·6 mM carboxypyridine disulfide (CPDS), which is another molecule able to react specifically with sulfhydryl groups on membranes, is affected in a similar way by NSAID. According to the well known involvement of sulfhydryl groups in inflammatory reactions, this peculiar effect of NSAID on the availability of membrane sulfhydryl groups, especially of lymphoid cells, could be related to some of their clinical properties.