Action of gold salts in some inflammatory and immunological models

Abstract

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.

Effect of gold salts,d-penicillamine and benoxaprofen on type II collagen-induced arthritis in rats

“…Interestingly, auranofin, but not GST, also reduced serum copper in rat adjuvant arthritis [25]. The role of copper in inflammation has been the subject of much controversy and a clear explanation for its pharmacologic modulation as demonstrated !n this study still eludes us.…”

Meloxicam: A potent inhibitor of adjuvant arthritis in the Lewis rat

“…The strain we used is very sensitive. However, the relationship of adjuvant arthritis of the rat to human rheumatoid arthritis is limited, since there are conflicting reports on the effectiveness of disease modifying antirheumatic drugs (gold, D-penicillamine, chloroquine, hydroxychloroquine) in adjuvant arthritis [47][48][49][50][51]. Finally, tenidap, although classified among the group of disease modifying agents for rheumatoid arthritis [55], with regard to its influence on CRP, showed only weak effects in our adjuvant arthritis model.…”

Oral Gold Therapy (Auranofin) in Pemphigus vulgaris

“…AF has been shown to have anti-inflam matory activity as evidenced by inhibition of ultraviolet-induced erythema in guinea pigs [11] , decreased phagocytosis of Candida al bicans by human polymorphonuclear cell [12] ; human neutrophil chcmotaxis was also significantly impaired [13]. Polymorpho nuclear cells obtained from patients with RA who responded clinically to AF exhibit ed a 43% decrease in formyl-methionyl-lcucyl-phenylalanine (FMLP) induced lyso zyme release, while cells from nonrespond ing patients showed no change in lyso zyme release [13].…”