Protective effects of N-acetylcysteine and its amide derivative against toxic metals in vitro: Potential alternatives/adjuncts to traditional chelators

IF 4.6 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-12-01 Epub Date: 2025-09-24 DOI:10.1016/j.etap.2025.104825

Thomas W. Sawyer, Yanfeng Song

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引用次数: 0

Abstract

The protective efficacies of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) against the toxicity of compounds containing arsenic, cadmium, cobalt, chromium and mercury, were compared to those of dimercaprol, dimercaptosuccinic acid, 2,3-dimercaptopropanesulphonate, D-penicillamine, and derivatives of ethylenediamine tetraacetic acid and diethylenetriaminepentaacetic in CHO-K1 cells. Both NAC and NACA were found to confer protection against these metals, with comparable or better efficacy than many of the test chelators. Results from studies using the glutathione synthesis inhibitor buthionine sulphoximine were consistent with NAC/NACA protection being mediated through both GSH up-regulation and chelation. Given NAC’s activity against metal toxicity, widespread clinical use, parenteral or oral routes of administration, high clinical safety, low cost and ease of accessibility, it should be given consideration as a broad-spectrum protectant against toxic metal poisoning as a treatment or adjunct/combination treatment. Its more lipophilic derivative NACA, also warrants attention, especially in those cases where brain toxicity is a concern.

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n -乙酰半胱氨酸及其酰胺衍生物对有毒金属的体外保护作用：传统螯合剂的潜在替代品/辅助剂。

研究了n -乙酰半胱氨酸（NAC）和n -乙酰半胱氨酸酰胺（NACA）对含砷、镉、钴、铬和汞的化合物的保护作用，并与二巯基丙二酸、2,3-二巯基丙磺酸、d -青霉胺以及乙二胺四乙酸和二乙烯三胺五乙酸衍生物对CHO-K1细胞的保护作用进行了比较。NAC和NACA都被发现对这些金属具有保护作用，其效果与许多测试螯合剂相当或更好。使用谷胱甘肽合成抑制剂丁硫氨酸亚砜胺的研究结果与通过谷胱甘肽上调和螯合介导的NAC/NACA保护一致。鉴于NAC抗金属毒性的活性，广泛的临床应用，肠外或口服给药途径，高临床安全性，低成本和易于获取，应考虑将其作为一种广谱保护剂，用于治疗或辅助/联合治疗中毒性金属中毒。其更亲脂的衍生物NACA也值得关注，特别是在那些涉及脑毒性的情况下。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.