Effects of antirheumatic gold compounds on the conversion of xanthine dehydrogenase to oxidase in rabbit liver cytosol in vitro

Life Sciences
Satoru SakumaYohko Fujimoto

Abstract

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.

References

Apr 1, 1986·Journal of Clinical Gastroenterology·D GeltnerM Kori
Aug 1, 1973·Journal of Clinical Pharmacology·A LorberR Hollcraft
Jan 1, 1983·Scandinavian Journal of Rheumatology. Supplement·N L Gottlieb
Jan 13, 1997·Biochemical and Biophysical Research Communications·S SakumaT Fujita
Aug 1, 1997·Biochemical Society Transactions·D R BlakeZ Zhang

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Citations

Jul 3, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Satoru SakumaYohko Fujimoto
Feb 5, 2008·European Journal of Pharmacology·Maria Pia RigobelloAlberto Bindoli
Jul 19, 2011·Chemistry & Biodiversity·Katarína ValachováLadislav Soltés

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