A comparison of the anti-inflammatory effects of copper aspirinate and other copper salts in the rat and guinea pig

Abstract

A comparison of the anti-inflammatory (AI) activity of copper compounds in models of kaolin-induced paw oedema and u.v. erythema in the rat and guinea pig is described. The results demonstrated considerable species variation, the guinea pig being more sensitive to the AI and irritant effects of copper aspirinate and the other copper compounds. The route of administration of these compounds was also an important factor in interpreting AI activity obtained. Indeed, the counter-irritation effects of the copper compounds may be largely responsible for the AI activity obtained after subcutaneous administration. The comparison between copper aspirinate and aspirin, performed in order to determine whether a copper complex of an AI drug was more active than the parent AI compound, failed to produce a clear difference in activity although copper aspirinate was more effective than aspirin in certain cases. It is concluded that this study highlights the complexities of copper therapy against inflammatory processes and furthermore indicates the importance of species, the model of inflammation and route of drug administration in interpreting data obtained with copper containing compounds.

Copper and ceruloplasmin (Cp) concentrations during the acute inflammatory process in the rat

“…The exogenous administration of copper salts or complexes has proved to be beneficial in the treatment of both experimental inflammation [1][2][3][4][5] and rheumatoid arthritis [6][7][8]. Our present knowledge also indicates that endogenous copper plays a relevant role in the modulation of the inflammatory process.…”

The pharmacologic activity of complexes and mixtures with copper and salicylates or aminopyrine following oral dosing in rats

“…In guinea pigs copper aspirinate produced a much stronger antiinflammatory response than the parent ligand. This effect correlated with higher levels in serum copper measured concomitantly [12]. Copper aspirinate was also orally effective in the treatment of rheumatoid disorders in man [13].…”

“…In this case copper is very likely to be available only in the ionic form and it therefore undergoes the highly efficient homeostatic control of the organism that tends to prevent much of the metal from being assimilated. There is some evidence for copper activity after oral administration [5,6,[12][13][14]. In guinea pigs copper aspirinate produced a much stronger antiinflammatory response than the parent ligand.…”

Paw Inflammation Model in Dogs for Preclinical Pharmacokinetic/Pharmacodynamic Investigations of Nonsteroidal Anti-Inflammatory Drugs

“…Kaolin was selected as a phlogistic agent because it acts mainly as an inert foreign body. In rats, kaolin does not activate the complement cascade (Noordhoek et al, 1977) but rather triggers the release of kinins and prostaglandins (Lewis, 1978). When administered outside an articulation, it is eliminable through sterile abscess formation, an inflammation resolution that guarantees a lack of delayed side effects.…”