Effects of antirheumatic gold compounds on the conversion of xanthine dehydrogenase to oxidase in rabbit liver cytosol in vitro.
Effects of auranofin (AUR), aurothioglucose (AuTG) and aurothiomalate (AuTM) on the conversion of xanthine dehydrogenase (XD) to oxidase (XO) in the cytosolic fraction from rabbit liver were examined. AUR had no effect on the conversion of XD to XO at concentrations up to 50 microM, whereas at concentrations ranging from 10 to 25 microM, AuTG and AuTM induced the conversion of XD to XO. The constituents of AuTG and AuTM, aurous ion (Au+), but not mercaptosuccinic acid and 1-thio-beta-D-glucose, converted XD to XO in a similar degree to AuTG and AuTM. This means that Au (I) moiety has an important role in the AuTG- and AuTM-induced conversion of XD to XO. Furthermore, N-acetyl-L-cysteine (NAC) and British anti-Lewisite (BAL) reconverted AuTG and AuTM-induced XO to XD, implying that clinical activity of NAC and BAL against toxic reactions of AuTG and AuTM is partially due to the XO reconversion. These results suggest that AuTG and AuTM have the potential to convert XD to its reactive oxygen species-generating form, XO, and that this effect may be correlated with cytotoxic actions of these drugs.
Sakuma
Satoru
S
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan. sakuma@gly.oups.ac.jp
Gotoh
Kyohko
K
Sadatoku
Namiko
N
Fujita
Tadashi
T
Fujimoto
Yohko
Y
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D006051:Aurothioglucose / Q000494:pharmacology; D002458:Cell Fractionation; D003600:Cytosol / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D018501:Antirheumatic Agents; D017382:Reactive Oxygen Species; D006052:Gold Sodium Thiomalate; D006051:Aurothioglucose; D001310:Auranofin; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase