Anti-oxidant and pro-oxidant behaviour of bucillamine.

Bucillamine (BUC) is used clinically for the treatment of rheumatoid arthritis. Some of the pharmacological action of BUC has been reported as being dependent on the production of reactive oxygen species (ROS). In this paper the reactivity of BUC with superoxide anion radical (O₂^•−) generated from potassium superoxide/18-crown-6 ether dissolved in DMSO, hydroxyl radical (HO^•) produced in the Cu²⁺-H₂O₂ reaction, peroxyl radical (ROO^•) from 2,2′-azobis (2-amidino-propane) dichloride decomposition, and singlet oxygen (¹O₂) from a mixture of alkaline aqueous H₂O₂ and acetonitrile, have been investigated. Chemiluminescence, fluorescence, electron paramagnetic resonance (EPR) spin-trapping techniques and the deoxyribose and oxygen radical absorbance capacity towards ROO^• (ORAC_ROO) assays were used to elucidate the anti- and pro-oxidative behaviours of BUC towards ROS. The results indicated that BUC efficiently inhibited chemiluminescence from the O₂^•−-generating system at relatively high concentrations (0.5-2 mmol/L); however, at lower concentrations (<0.5 mmol/L) the drug enhanced light emission. The behaviour of BUC was correlated with a capacity to decrease the chemiluminescence signal from the Cu²⁺-H₂O₂ system; scavenging HO^• was effective only at high concentrations (1-2 mmol/L) of the drug. Bucillamine also prevented deoxyribose degradation induced by HO^• in a dose-dependent manner, reaching maximal inhibition (24.5%) at a relative high concentration (1.54 mmol/L). Moreover, BUC reacts with ROO^•; the relative ORAC_ROO was found to be 0.34 µmol/L Trolox equivalents/µmol sample. The drug showed quenching of ¹O₂-dependent 2,2,6,6-tetramethylpiperidine-N-oxide radical formation from 2,2,6,6-tetramethyl-piperidine (e.g. 90% inhibition was found at 1 mmol/L concentration). The results showed that BUC may directly scavenge ROS or inhibit reactions generating them. However, the drug may have pro-oxidant activity under some reaction conditions. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]