Several
gold salts were compared in
kaolin-induced rat paw oedema, u.v.
erythema in guinea pigs, delayed type
hypersensitivity and humoral immunity in mice, and adjuvant-induced
arthritis in the rat. In the latter the additional parameters of serum
gold and
copper levels and lysosomal
enzyme activity were determined. In addition, the in vitro inhibition of several lysosomal
enzymes derived from mouse macrophages was studied. The
gold compounds examined were
aurothiomalate,
aurothioglucose,
triethylphosphine gold chloride (
SK & F 36914) and its glucopyranoside derivative (
SK & F D-39162),
triphenylphosphine gold chloride and
sodium gold chloride dihydrate.
SK & F 36914 and SK & F D-39162 has significant activity after oral dosage upon paw
kaolin and u.v.
erythema in rats and guinea pigs, respectively. Gastric swelling also occurred. In Wistar rats,
adjuvant arthritis was little affected by the
gold salts but in the Lewis rats there was suppression. In both strains there was less elevation in serum
copper levels with treatment by
SK & F 36914 and SK & F D-39162, but not by
aurothiomalate. None of the compounds had any measurable effect on
delayed hypersensitivity or humoral antibody levels in mice. The in vitro activities of
cathepsin B1 and
cathepsin D were inhibited by all the
gold compounds. Reactivity of
gold compounds with
glutathione and
cysteine in vitro was dependent on compound solubility and the nature of the
gold ligand. Considerable differences exist between the profiles of activity for the different
gold salts evaluated. These observations indicate that some
gold salts do possess anti-inflammatory activity with a potency similar to that of
indomethacin.