ijms-logo

Journal Browser

Journal Browser

Relationships between Organ Toxicity and Metals

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: closed (31 December 2021) | Viewed by 9951

Special Issue Editors


E-Mail Website
Guest Editor
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
Interests: organ and tissue structure and ultrastructure

E-Mail Website
Guest Editor

Special Issue Information

Dear Colleagues,

It has been reported that metals such as cobalt, copper, chromium, iron, magnesium, manganese, molybdenum, nickel, selenium and zinc are essential nutrients required for various biochemical and physiological functions in plants and animals. Inadequate supply of these micro-nutrients results in a variety of deficiency diseases or syndromes. Their toxicity depends on several factors including dose, route of exposure, and chemical species, as well as age, gender, genetics, and nutritional status of exposed individuals. Metals, and in particular heavy metals, are considered systemic toxicants that are known to induce multiple-organ damage, even at lower levels of exposure and they are also classified as human carcinogens.

This Special Issue is focused on organ toxicity and it would include original articles and review on aspects related with molecular and pharmacological mechanisms of organ toxicity induced by different metals. Potential topics include, but are not limited to, intracellular targets, reactive oxygen species, apoptosis, and morphological aspects.

Prof. Dr. Antonio Micali
Prof. Dr. Letteria Minutoli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Metals
  • Organ toxicity
  • Oxidative stress
  • Inflammation
  • Apoptosis
  • Carcinogenesis

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

11 pages, 3052 KiB  
Article
Methylmercury Causes Neurodegeneration and Downregulation of Myelin Basic Protein in the Spinal Cord of Offspring Rats after Maternal Exposure
by Diane Cleydes Baía da Silva, Leonardo Oliveira Bittencourt, Daiane Claydes Baia-da-Silva, Victoria Santos Chemelo, Luciana Eiró-Quirino, Priscila Cunha Nascimento, Márcia Cristina Freitas Silva, Marco Aurelio M. Freire, Walace Gomes-Leal, Maria Elena Crespo-Lopez and Rafael Rodrigues Lima
Int. J. Mol. Sci. 2022, 23(7), 3777; https://doi.org/10.3390/ijms23073777 - 29 Mar 2022
Cited by 4 | Viewed by 2159
Abstract
Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects [...] Read more.
Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects of maternal exposure to MeHg during gestation and lactation on the spinal cord of offspring. Pregnant rats received oral doses of MeHg (40 μg/kg/day) over a period of 42 days (21 gestation and 21 lactation). Control animals received the vehicle only. Total mercury concentration was measured in blood samples from offspring collected at the 41st postnatal day. Counting of motor neurons and immunoreactivity for myelin basic protein (MBP) were assessed in the spinal cords in both control and MeHg-intoxicated animals. Our results showed that MeHg promoted an increase in blood Hg levels. In addition, it caused a reduction in the number of spinal cord motor neurons as well as decreased MBP immunoreactivity in the cervical, thoracic and lumbar segments. Our present findings suggest that MeHg intoxication during rat pregnancy and lactation is associated with a pattern of motor neuron degeneration and downregulation of myelin basic protein in different segments of a developing spinal cord. Further studies are needed to establish the effect of MeHg intoxication in both young and adult rats. Full article
(This article belongs to the Special Issue Relationships between Organ Toxicity and Metals)
Show Figures

Figure 1

16 pages, 4638 KiB  
Article
Salivary Glands after Prolonged Aluminum Exposure: Proteomic Approach Underlying Biochemical and Morphological Impairments in Rats
by Deiweson Souza-Monteiro, Márcia Cristina dos Santos Guerra, Leonardo Oliveira Bittencourt, Walessa Alana Bragança Aragão, Aline Dionizio, Felipe Martins Silveira, Marília Afonso Rebelo Buzalaf, Manoela Domingues Martins, Maria Elena Crespo-Lopez and Rafael Rodrigues Lima
Int. J. Mol. Sci. 2022, 23(4), 2251; https://doi.org/10.3390/ijms23042251 - 18 Feb 2022
Cited by 6 | Viewed by 2044
Abstract
Aluminum (Al) is one of the most abundant elements on Earth, and its high extraction rate and industrial use make human exposure very common. As Al may be a human toxicant, it is important to investigate the effects of Al exposure, mainly at [...] Read more.
Aluminum (Al) is one of the most abundant elements on Earth, and its high extraction rate and industrial use make human exposure very common. As Al may be a human toxicant, it is important to investigate the effects of Al exposure, mainly at low doses and for prolonged periods, by simulating human exposure. This work aimed to study the effects of low-dose exposure to chloride aluminum (AlCl3) on the oxidative biochemistry, proteomic profile, and morphology of the major salivary glands. Wistar male rats were exposed to 8.3 mg/kg/day of AlCl3 via intragastric gavage for 60 days. Then, the parotid and submandibular glands were subjected to biochemical assays, proteomic evaluation, and histological analysis. Al caused oxidative imbalance in both salivary glands. Dysregulation of protein expression, mainly of those related to cytoarchitecture, energy metabolism and glandular function, was detected in both salivary glands. Al also promoted histological alterations, such as acinar atrophy and an increase in parenchymal tissue. Prolonged exposure to Al, even at low doses, was able to modulate molecular alterations associated with morphological impairments in the salivary glands of rats. From this perspective, prolonged Al exposure may be a risk to exposed populations and their oral health. Full article
(This article belongs to the Special Issue Relationships between Organ Toxicity and Metals)
Show Figures

Figure 1

20 pages, 6839 KiB  
Article
Is Cadmium Toxicity Tissue-Specific? Toxicogenomics Studies Reveal Common and Specific Pathways in Pulmonary, Hepatic, and Neuronal Cell Models
by Matilde Forcella, Pierre Lau, Marco Fabbri, Paola Fusi, Monica Oldani, Pasquale Melchioretto, Laura Gribaldo and Chiara Urani
Int. J. Mol. Sci. 2022, 23(3), 1768; https://doi.org/10.3390/ijms23031768 - 4 Feb 2022
Cited by 8 | Viewed by 2211
Abstract
Several harmful modifications in different tissues-organs, leading to relevant diseases (e.g., liver and lung diseases, neurodegeneration) are reported after exposure to cadmium (Cd), a wide environmental contaminant. This arises the question whether any common molecular signatures and/or Cd-induced modifications might represent the building [...] Read more.
Several harmful modifications in different tissues-organs, leading to relevant diseases (e.g., liver and lung diseases, neurodegeneration) are reported after exposure to cadmium (Cd), a wide environmental contaminant. This arises the question whether any common molecular signatures and/or Cd-induced modifications might represent the building block in initiating or contributing to address the cells towards different pathological conditions. To unravel possible mechanisms of Cd tissue-specificity, we have analyzed transcriptomics data from cell models representative of three major Cd targets: pulmonary (A549), hepatic (HepG2), and neuronal (SH-SY-5Y) cells. Further, we compared common features to identify any non-specific molecular signatures. The functional analysis of dysregulated genes (gene ontology and KEGG) shows GO terms related to metabolic processes significantly enriched only in HepG2 cells. GO terms in common in the three cell models are related to metal ions stress response and detoxification processes. Results from KEGG analysis show that only one specific pathway is dysregulated in a significant way in all cell models: the mineral absorption pathway. Our data clearly indicate how the molecular mimicry of Cd and its ability to cause a general metal ions dyshomeostasis represent the initial common feature leading to different molecular signatures and alterations, possibly responsible for different pathological conditions. Full article
(This article belongs to the Special Issue Relationships between Organ Toxicity and Metals)
Show Figures

Graphical abstract

20 pages, 6077 KiB  
Article
Increased Endocytosis of Cadmium-Metallothionein through the 24p3 Receptor in an In Vivo Model with Reduced Proximal Tubular Activity
by Itzel Pamela Zavala-Guevara, Manolo Sibael Ortega-Romero, Juana Narváez-Morales, Tania Libertad Jacobo-Estrada, Wing-Kee Lee, Laura Arreola-Mendoza, Frank Thévenod and Olivier Christophe Barbier
Int. J. Mol. Sci. 2021, 22(14), 7262; https://doi.org/10.3390/ijms22147262 - 6 Jul 2021
Cited by 12 | Viewed by 2741
Abstract
Background: The proximal tubule (PT) is the major target of cadmium (Cd2+) nephrotoxicity. Current dogma postulates that Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway [...] Read more.
Background: The proximal tubule (PT) is the major target of cadmium (Cd2+) nephrotoxicity. Current dogma postulates that Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney. Nevertheless, there is evidence that the distal parts of the nephron are also sensitive to damage induced by Cd2+. In rodent kidneys, another receptor for protein endocytosis, the 24p3 receptor (24p3R), is exclusively expressed in the apical membranes of distal tubules (DT) and collecting ducts (CD). Cell culture studies have demonstrated that RME and toxicity of CdMT and other (metal ion)–protein complexes in DT and CD cells is mediated by 24p3R. In this study, we evaluated the uptake of labeled CdMT complex through 24p3R after acute kidney injury (AKI) induced by gentamicin (GM) administration that disrupts PT function. Subcutaneous administration of GM at 10 mg/kg/day for seven days did not alter the structural and functional integrity of the kidney’s filtration barrier. However, because of PT injury, the concentration of the renal biomarker Kim-1 increased. When CdMT complex coupled to FITC was administered intravenously, both uptake of the CdMT complex and 24p3R expression in DT increased and also colocalized after PT injury induced by GM. Although megalin decreased in PT after GM administration, urinary protein excretion was not changed, which suggests that the increased levels of 24p3R in the distal nephron could be acting as a compensatory mechanism for protein uptake. Altogether, these results suggest that PT damage increases the uptake of the CdMT complex through 24p3R in DT (and possibly CD) and compensate for protein losses associated with AKI. Full article
(This article belongs to the Special Issue Relationships between Organ Toxicity and Metals)
Show Figures

Figure 1

Back to TopTop