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Metal Toxicity in Animals: Recent Insights on Physiological and Molecular Aspects

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 2006

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Department of Biology, University of Naples, Federico II, 80126 Naples, Italy
Interests: cytotoxicology; environmental toxicology; metals toxicity; oviparous vertebrates development; reproductive toxicology
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Special Issue Information

Dear Colleagues,

Heavy metals are one of the oldest known toxicants. Despite this, their presence in the environment is still increasing, as is the presence and bioaccumulation of other metals, which show multiple industrial, domestic, agricultural, medical, and technological applications. Among them, the toxic action of rare earth elements (or lanthanides) is of particular concern. Metals that have no biological functions share pathways through which essential elements are transported into an organism, thus disrupting key cellular functions. Exposure to these heterogenous class of metals is associated with an increased risk of cancer, metabolic disorders, neurodevelopmental effects, genotoxicity, and immunotoxicity, in humans and animals. In addition, scientific studies are highlighting the adverse effects of exposure to a mixture of different environmental contaminants. The risk assessment of a single metal may generate data that underestimate the toxic potential of the substance in the environment.

This Special Issue welcomes original research and reviews on the physiological and molecular pathways modified by metals. Articles focusing on the combined effects of mixtures of different metals, or mixtures of metals and other pollutants, aimed at understanding how they can cause toxicity or disease, the molecular interactions that can occur, the potentiating and synergistic effects that can cause an unexpected toxicological response or an attack on another target organ, are particularly welcome.

Prof. Dr. Rosaria Scudiero
Guest Editor

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Keywords

  • heavy metals
  • lanthanides
  • physiological and molecular pathways of cellular toxicology
  • environmental pollution
  • risk assessments
  • risk of mixing contaminants

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Published Papers (2 papers)

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17 pages, 4396 KiB  
Article
Investigation of the Neurotoxicity Mechanisms of Ni2+ in Rat Neocortical Neurons Through Transcriptome Analysis
by Chen Meng, Yang Lu, Yan Huang and Xiaoying Lü
Int. J. Mol. Sci. 2025, 26(9), 4014; https://doi.org/10.3390/ijms26094014 - 24 Apr 2025
Abstract
The cytotoxic effects of Ni2+ released from nickel-based alloy implants on tissues have been a longstanding research focus in biocompatibility studies. However, investigations into the neurotoxicity of Ni2+ remain relatively limited. Building on our previous findings that Ni2+ can rapidly [...] Read more.
The cytotoxic effects of Ni2+ released from nickel-based alloy implants on tissues have been a longstanding research focus in biocompatibility studies. However, investigations into the neurotoxicity of Ni2+ remain relatively limited. Building on our previous findings that Ni2+ can rapidly affect the excitability of neuronal networks, this study further investigated the neurotoxic effects of prolonged Ni2+ exposure. First, the cytotoxicity effects of Ni2+ on rat neocortical neurons in vitro were evaluated by MTT cell viability assay, and changes in the length of the axon initial segment of neurons caused by Ni2+ exposure were quantified. Next, transcriptome sequencing was employed to identify differentially expressed genes (DEGs) induced by Ni2+ treatment, and four DEGs—Hk2, Ldha, Cd9, and Nfasc—were selected for qRT-PCR validation. The ATP content of neurons was measured to assess cellular energy metabolism under Ni2+ influence. Finally, by comparing these experimental results with our previous findings, this study explored the neurotoxicity mechanisms of Ni2+ and analyzed the correlation between its neurotoxicity and cytotoxicity. This study revealed that the neurotoxicity mechanisms of Ni2+ are associated with the concentration of Ni2+ and the duration of its action. When at low concentrations or with short exposure times, Ni2+ suppresses the excitability of the neuronal networks by rapidly blocking Ca2+ channels, whereas at high concentrations or with prolonged exposure, it further inhibits the network’s excitability by activating the HIF-1α pathway and inducing obvious cytotoxicity. Full article
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15 pages, 1758 KiB  
Article
Metalloproteomic Investigation of Hg-Binding Proteins in Renal Tissue of Rats Exposed to Mercury Chloride
by Emerson Carlos de Almeida, Victor Diego Faria, Felipe Dalmazzo Cirinêu, Maria G. A. Santiago, Beatriz Miotto, José C. S. Vieira, Camila Pereira Braga, Jiri Adamec, Ana A. H. Fernandes, Marília A. R. Buzalaf and Pedro de Magalhães Padilha
Int. J. Mol. Sci. 2024, 25(1), 164; https://doi.org/10.3390/ijms25010164 - 21 Dec 2023
Cited by 3 | Viewed by 1438
Abstract
Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to [...] Read more.
Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg−1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 “upregulated” proteins (p > 0.95) and 47 “downregulated” proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg−1, which qualifies these proteins as potential mercury-exposure biomarkers. Full article
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