Copper: Toxicological relevance and mechanisms. Original paper

What was studied?

This study examined the toxicological relevance of copper (Cu) and the mechanisms by which excess Cu leads to cellular damage. It explored how Cu imbalance affects various biological systems, contributing to diseases like liver disorders, neurodegeneration, and oxidative stress. The authors reviewed how Cu toxicity induces cellular damage via its redox activity, leading to the generation of reactive oxygen species (ROS), which cause DNA damage, lipid peroxidation, and protein dysfunction. The paper also discussed the regulatory systems in place to control Cu homeostasis, the molecular transport mechanisms involved, and the role of Cu-related diseases like Wilson’s and Menkes disease.

Who was studied?

The study primarily focused on research conducted on humans, animal models, and cell cultures to examine the effects of copper overload and deficiency. It emphasized conditions like Wilson’s disease, a genetic disorder causing Cu accumulation in tissues, particularly the liver, brain, and corneas. The authors also referenced studies on liver dysfunction, neurodegenerative diseases, and other Cu-related disorders to illustrate the broad implications of Cu imbalance. Through the analysis of Cu transport and homeostasis, the study connected Cu’s impact on health to a range of physiological and biochemical processes.

Most important findings

The study highlighted Cu-induced oxidative stress as the most significant factor in Cu toxicity. Copper’s ability to cycle between Cu(II) and Cu(I) states enables it to generate ROS, including hydroxyl radicals, which cause damage to lipids, proteins, and DNA. The authors also identified key Cu-binding proteins and chaperones, like ceruloplasmin and metallothionein, that help manage Cu transport and storage to prevent toxicity. However, when Cu homeostasis is disrupted, as in Wilson’s disease, Cu accumulates in tissues, leading to liver damage, neurodegeneration, and other serious complications. The study also linked lipid metabolism and gene expression alterations to Cu toxicity, suggesting that these may be early markers of Cu-induced cellular damage. Furthermore, oxidative damage was strongly implicated in the pathogenesis of diseases like Alzheimer’s, Parkinson’s, and Huntington’s diseases due to Cu’s ability to generate harmful ROS in the brain.

Key implications

This study underscores the critical role of Cu homeostasis in maintaining health. Disruptions in Cu balance can lead to severe toxic effects, highlighting the importance of regulating Cu levels in both clinical and environmental settings. For microbiome signatures, clinicians could consider Cu-induced oxidative stress as a potential factor contributing to microbial dysbiosis, especially in individuals with Cu overload or deficiency. Targeting the Cu transport system or Cu-binding proteins may provide therapeutic avenues for treating Cu-related diseases. Moreover, measuring serum ceruloplasmin levels and using genetic markers for Cu transport could serve as valuable biomarkers for diagnosing Cu toxicity early, especially in patients at risk for conditions like Wilson’s disease or neurodegenerative disorders.