Antioxidant properties of bucillamine: Possible mode of action

doi:10.1016/j.bbrc.2006.08.155

Biochemical and Biophysical Research Communications

Volume 349, Issue 3, 27 October 2006, Pages 1171-1175

https://doi.org/10.1016/j.bbrc.2006.08.155 Get rights and content

Abstract

The antioxidant properties of Bucillamine (BUC), a di-thiol compound used for treatment of rheumatoid arthritis (RA) and its possible mode of action, were investigated. BUC exhibits potent antioxidant activity similar to those of trolox and ascorbic acid. It reduces the stable free radical diphenyl-2-picrylhydrazyl (DPPH) with IC₅₀ of 18.5 ± 0.1 μmol, its relative antioxidant activity by the ferric reducing ability (FRAP) is 2.07 ± 0.01 mM and by the trolox equivalent antioxidant capacity (TEAC), 1.46 ± 0.05 mM. However, its superoxide and apparent hydroxyl radical scavenging activities are low (IC₅₀ at millimolar concentrations). We found that BUC is a strong iron (II) and copper (II) chelator. This finding is very important since these metal ions are significantly higher in RA patients and may be involved in oxidative stress-induced damage. Our study suggests that BUC is a potent antioxidant which exerts its beneficial therapeutic activities in RA patients by metal chelation rather than by scavenging free radical species.

Section snippets

Materials and methods

All reagents were of analytical grade, obtained from Sigma Aldrich Chemical Co. (Israel). Bucillamine of high chemical purity was purchased from GreenSyn (Guangzhou) Co., Ltd., China.

Cyclic voltammetric studies were carried out by an EG&G Princeton Applied Research potentiostat galvanostat, model 263 A, using a three-electrode assembly consisting of a glassy carbon working electrode (A = 0.07 cm²), a platinum counter electrode, and a saturated calomel as a reference electrode.

Antioxidant activity

Results

The antioxidant activity of BUC and other antioxidants was evaluated by the TEAC and FRAP assays and the results are shown in Table 1. By both methods BUC had a high relative antioxidant activity, 1.46 ± 0.06 and 2.07 ± 0.01 mM, as compared with trolox 1.00 ± 0.0 and 1.75 ± 0.02, and ascorbic acid, 0.99 ± 0.02 and 1.95 ± 0.02 mM, respectively.

The scavenging activity of the DPPH radical was evaluated. As shown in Table 2, the concentration providing 50% of the radical scavenging (IC₅₀) was determined. A lower

Discussion

The aim of this study was to evaluate the in vitro antioxidant properties and possible mode of action of the thiol-containing drug Bucillamine, the efficacy of which in the treatment of rheumatoid arthritis is well documented [22], [23], [24]. We used a panel of tests to assess its antioxidant activity, using biologically relevant oxygen-derived species to test its scavenging capacity. BUC, a di-thiol, showed effective and potent antioxidant activity albeit poor scavenging capacity against the

Acknowledgment

This study was supported in part by a Grant from the Israel Science Foundation.

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Antioxidant properties of bucillamine: Possible mode of action

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgment

Free. Radic. Biol. Med

Clin. Immunol. Immunopathol.

Food Chem. Toxicol.

Lebensmittel-Wissenschaft Technol.

Analyt. Biochem.

Pharmacol. Res.

Analyt. Biochem.

Biochim. Biophys. Acta

Free Radic. Biol. Med.

Int. J. Immunopharmacol.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Clin. Chim. Acta

Int. J. Immunopharmacol.

Antioxidants in human health and disease

Ann. Rev. Nutr.