Biochemistry active substances from microorganisms. IV. Establishment of several in vitro anti-inflammatory probes applicable to microbial broths the effects of non-steroidal anti-inflammatory drugs and antibiotics on them.

Abstract

Four assay systems, i. e. membrane stabilization, inhibition of protein denaturation, and inhibition of collagen- and ADP-induced platelet aggregation, were examined for possible use as in vitro anti-inflammatory screening probes applicable to microbial metabolites. All these systems were simple and reasonably selective for known platelet anti-aggregants or non-steroidal anti-inflammatory agents. As regards sensitivity, detection should be possible at levels of several to several hundred μg/ml for an indomethacin class substance existing in the broth ; such concentrations are attainable in the broth in the case of useful antibiotic production. Each system was hardly disturbed by medium components in the broth and the procedures were successfully applied to actinomycetes cultures. Upon examination of typical non-steroidal anti-inflammatory drugs to determine their effects on these systems, it was found that they could be classified into four distinct types in terms of their mode of action. The correlation of these effects with results in several in vivo models is discussed. Furthermore, the effects of various antibiotics including several types of ionophores on these probes were thoroughly studied.