Salicylate and enzymes

Abstract

Salicylate inhibits the activities of a number of cellular enzymes and in some instances the mechanisms of inhibition have been established (Smith, 1968a). Reported inhibitory actions of the salicylate ion on important enzyme systems in vitro are now reviewed and assessed in relation to the known clinical and toxic effects of the drug.

Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo

“…The compositions of in vitro incubation mixtures vary much more widely than those present in the cells of the body. The relative proportions of enzymes, substrates, cofactors, the pH and ionic constituents of the incubation media may bear little resemblance to physiological requirements [16]. The concentration of a drug in vivo may vary with both tissue and time in the body, whereas in vitro it will remain relatively constant.…”

Aspirin, salicylate and prostaglandins

“…These two activities are not synonymous. Not only are there independent effects of the drug on prostaglandin biosynthesis and leucocyte migration but also the concentrations of salicylate ion which accumulate in inflammatory exudates in the rat are such that they interfere with many enzyme systems other than prostaglandin synthetase [19]. Some of these enzyme systems may play important roles in the development of inflammatory responses.…”

Chairman's introduction Determinants of inflammation test selection:In vitro orin vivo?

“…This largely symptomatic approach led to an array of proposed biochemical bases of the mode(s) of action of nonsteroidal anti-inflammatory drugs (NSAIDs) [1]. With the demonstration that the majority of NSAIDs were inhibitors of cyclooxygenase, a unifying concept for anti-inflammatory action was brought into being, which provided a mechanistic basis for the development of newer, more potent drugs.…”