Distribution of the acetyl compared with the salicyl moiety of acetylsalicylic acid. Acetylation of macromolecules in organs wherein side-effects are manifest.

The distribution in rats of the acetyl group of aspirin has been compared with that of the salicyl moiety with the objective of establishing if: (1) there are differences in their biodisposition which might be important in the development of side- or therapeutic effects of aspirin, and (2) the range of organs and biomolecules therein which are acetylated by aspirin. Using whole-body autoradiography and liquid scintillation counting techniques it was found that the acetyl group of 3H- or 14C-acetyl-labelled aspirin became bound to a wide variety of proteins, glycoproteins and lipids of the glandular and non-glandular region of the stomach, kidney, liver and to a lesser extent bone marrow, i.e. organs in which side-effects are frequently encountered. It is suggested that: (1) the acetylation of biomolecules may be a major factor in the development of side-effects in these organs, and (2) in addition to acetylation of prostaglandin synthetase, the acetylation of enzymes and other biomolecules may have a much wider bearing on the biochemical changes underlying the development of these side-effects. Acetylation of the protein/macromolecular components was especially pronounced in inflamed (c.f. control) hindpaws of carrageenan-injected rats. This could be a result of acetylation of the drug-carrier protein, albumin, and other proteins carried into inflamed tissues and this acetylation could have marked consequences for the functions of these proteins.