Effects of auranofin and myochrysine

Auranofin (SKF-D 39162) is an oral gold preparation for the treatment of rheumatoid arthritis. One of its major side effects is diarrhoea. To determine one possible mechanism for this we compared the effects of auranofin and myochrysine on intestinal water and solute transport in the rat. Jejunal perfusion with 2 mM auranofin (n=5) induced fluid and electrolyte secretion and inhibited glucose absorption (p<0-01). Auranofin (0-2 mM) induced fluid secretion in the jejunum (n=5; p<001) and colon (n=6; p<0O01). In contrast, 2 mM myochrysine enhanced jejunal water and electrolyte absorption (n=6; p<0-02). Both compounds enhanced absorption of mannitol (p<0-01). Perfusion of 0.2mM auranofin for two hours had no significant effect on mucosal c-AMP levels (n=4). After perfusion for two hours with 2 mM auranofin the jejunal mucosa showed severe injury by light and scanning electronmicroscopy while myochrysine had no apparent effect. The damage after perfusion with 0-2 mM auranofin for two hours was less severe. Auranofin was more rapidly absorbed than myochrysine (p<0.05). These effects provide an explanation for the diarrhoea associated with auranofin therapy.