ArticleFree radical biology & medicine2013
Role of direct reactivity with metals in chemoprotection by N-acetylcysteine against chromium(VI), cadmium(II), and cobalt(II).
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 72 citations in OpenAlex.
- Damage to newly synthesized proteins is a major cause of Cd(II) toxicity counteracted by proteasomes and integrated stress response in human cells.Chemico-biological interactions · 2026Article
- Nuclear SUMOylation and Proteotoxic Stress Responses to Metals with Different Ligand Preferences.Chemical research in toxicology · 2025Article
- Recent advances in the clinical management of intoxication by five heavy metals: Mercury, lead, chromium, cadmium and arsenic.Heliyon · 2025Review
- Heavy metal pollution and ischemic stroke: multimechanistic pathogenesis and countermeasures.Frontiers in public health · 2025Review
- Cobalt ions induce a cellular senescence secretory phenotype in human synovial fibroblast-like cells that may be an early event in the development of adverse local tissue reactions to hip implants.Osteoarthritis and cartilage open · 2024Article
- Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.Biologics : targets & therapy · 2024Review
- Antagonistic effects of N-acetylcysteine on lead-induced apoptosis and oxidative stress in chicken embryo fibroblast cells.Heliyon · 2023Article
- Effects of N-Acetylcysteine Supplementation on Oxidative Stress and Expression of Apoptosis-Related Genes in Testicular Tissue of Rats Exposed to Lead.Biological trace element research · 2023Article
- The association of cobalturia with cobaltism symptoms a prospective blinded study of 229 post-arthroplasty patients.PloS one · 2023Article
- Direct Interaction betweenAntioxidants (Basel, Switzerland) · 2022Review
- Article
- Synthetic Amphoteric Cryogels as an Antidote against Acute Heavy Metal Poisoning.Molecules (Basel, Switzerland) · 2021Article
- N-acetylcysteine restores the cadmium toxicity of Caenorhabditis elegans.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- NADCell cycle (Georgetown, Tex.) · 2021Article
- A case report of cobalt cardiomyopathy leading to electric storm and cardiogenic shock: the importance of the orthopaedic background in patients with heart failure of unknown aetiology.European heart journal. Case reports · 2021Article
- Epalrestat suppresses cadmium-induced cytotoxicity through Nrf2 in endothelial cells.Experimental and therapeutic medicine · 2021Article
- Protonation Equilibria ofACS omega · 2020Article
- N-Acetyl-Cysteine Reduces Blood Chromium and Cobalt Levels in Metal-on-Metal Hip Arthroplasty.Arthroplasty today · 2020Article
- Article
- Toxicological Antagonism among Welding Fume Metals: Inactivation of Soluble Cr(VI) by Iron.Chemical research in toxicology · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The antioxidant N-acetylcysteine (NAC) is widely used for the assessment of the role of reactive oxygen species (ROS) in various biological processes and adverse drug reactions. NAC has been found to effectively inhibit the toxicity of carcinogenic metals, which was attributed to its potent ROS-suppressive properties. However, the absence of redox activity among some metals and findings from genetic models suggested a more diverse, smaller role of oxidative stress in metal toxicity. Here, we examined mechanisms of chemoprotection by NAC against Cd(II), Co(II), and Cr(VI) in human cells. We found that NAC displayed a broad-spectrum chemoprotective activity against all three metals, including suppression of cytotoxicity, apoptosis, p53 activation, and HSP72 and HIF-1α upregulation. Cytoprotection by NAC was independent of cellular glutathione. NAC strongly inhibited the uptake of all three metals in histologically different types of human cells, explaining its high chemoprotective potential. A loss of Cr(VI) accumulation by cells was caused by NAC-mediated extracellular reduction of chromate to membrane-impermeative Cr(III). Suppression of Co(II) uptake resulted from a rapid formation of Co(II)-NAC conjugates that were unable to enter cells. Our results demonstrate that NAC acts through more than one mechanism in preventing metal toxicity and its chemoprotective activity can be completely ROS-independent. Good clinical safety and effectiveness in Co(II) sequestration suggest that NAC could be useful in the prevention of tissue accumulation and toxic effects of Co ions released by cobalt-chromium hip prostheses.
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