Auranofin treatment of rats: adaptation to intestinal adverse effects and observations on the cytosolic distribution of gold in the intestines, liver and kidneys.
The possibility of development of adaptation to intestinal adverse effects of auranofin (AF), a gold-containing anti-arthritic drug, was investigated in rats. Groups of 6 rats received orally 0.0, 2.5 or 10.0 mg AF/kg daily for one week, and 20.0 mg AF/kg daily the next week. During the first week all animals had normal stools. During the second week, those on 0.0 or 2.5 mg AF/kg the preceding week developed persistent loose stools, whereas those on 10.0 mg AF/kg the preceding week did not. At the end of the second week, no differences in the intestinal cytosolic gold concentrations were detected, which could be related to the dose regimen or the loose stools. Gel filtration profiles of gold from intestinal, liver and kidney cytosols following AF treatment, were compared with gold profiles following in vitro incubation of AF with cytosols obtained from non-treated rats. In the in vivo situation, but not in vitro, gold peaked with proteins of mol. wt. about 10,000 in the small intestine and kidneys. Up to 20% of the cytosolic gold was recovered in these fractions in the small intestine. These proteins eluted slightly different from metallothionein on gel filtration. The cellular mechanisms involved in the demonstrated adaptation to intestinal adverse effects from AF, are not clear, judged from the present study.
D000818:Animals; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D003600:Cytosol / Q000378:metabolism*; D003967:Diarrhea / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006046:Gold / Q000031:analogs & derivatives*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold