Effects of auranofin and myochrysine on intestinal transport and morphology in the rat.
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 less than 0.01). Auranofin (0.2 mM) induced fluid secretion in the jejunum (n = 5; p less than 0.01) and colon (n = 6; p less than 0.01). In contrast, 2 mM myochrysine enhanced jejunal water and electrolyte absorption (n = 6; p less than 0.02). Both compounds enhanced absorption of mannitol (p less than 0.01). Perfusion of 0.2 mM 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 less than 0.05). These effects provide an explanation for the diarrhoea associated with auranofin therapy.
D000818:Animals; D001310:Auranofin / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D005947:Glucose / Q000493:pharmacokinetics; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000648:ultrastructure; D007422:Intestines / Q000187:drug effects*; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011919:Rats, Inbred Strains; D014882:Water-Electrolyte Balance / Q000187:drug effects
D006052:Gold Sodium Thiomalate; D001310:Auranofin; D008353:Mannitol; D005947:Glucose