Penicillamine has been widely-used clinically as a copper-chelating drug for the treatment of copper-overload in Wilson's disease. In this study, we found that penicillamine provided marked protection against cytotoxicity induced by tetrachlorohydroquinone (TCHQ), a major toxic metabolite of the well-known wood preservative pentachlorophenol, while other classic copper-chelating agents do not. We found, unexpectedly, that both TCHQ autooxidation and tetrachlorosemiquinone radical (TCSQ•-) formation were remarkably delayed by penicillamine. Further investigation showed that TCSQ•- was reduced back to TCHQ by penicillamine, with the concurrent formation of its corresponding disulfide. These data demonstrated that the protection by penicillamine against TCHQ-induced toxicity was not due to its classic Cu-chelating property, but rather to its reduction of the reactive TCSQ•- to the much less-reactive TCHQ. This is the first report of an unexpected antioxidant and redox activity for penicillamine, which might prove highly relevant to its biological activities.

中文翻译：

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经典的铜螯合剂青霉素胺具有出乎意料的抗氧化剂和氧化还原活性。

青霉胺在临床上已广泛用作铜螯合药，用于治疗威尔逊氏病中的铜超载。在这项研究中，我们发现青霉胺对由著名的木材防腐剂五氯苯酚的主要有毒代谢产物四氯氢醌（TCHQ）诱导的细胞毒性具有明显的保护作用，而其他经典的铜螯合剂则没有。我们出乎意料地发现，青霉素胺显着延迟了TCHQ自氧化和四氯半醌自由基（TCSQ•-）的形成。进一步的研究表明，青霉素可以将TCSQ•-还原为TCHQ，同时生成相应的二硫键。这些数据表明，青霉素胺对TCHQ诱导的毒性的保护作用并非归因于其经典的Cu螯合特性，而是将其反应性TCSQ•-减少为反应性较差的TCHQ。这是关于青霉素胺具有出乎意料的抗氧化剂和氧化还原活性的第一份报告，这可能与其生物活性高度相关。