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Medical Value of Metal Complexes and Plant-Derived Compounds: Biological Evaluation, Health Effects, Challenges, and Future Opportunities

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

Deadline for manuscript submissions: 20 March 2025 | Viewed by 2898

Special Issue Editors


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Department of Biomedicine and Environmental Research, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland
Interests: mechanisms of toxicity of selected elements; mechanisms of metal interactions; seeking the most sensitive biomarkers to assess organism reactions to some metals; cytotoxicity of metals; bioelements; oxidative stress; antioxidants; in vivo/in vitro studies; experimental toxicology
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Special Issue Information

Dear Colleagues,

Heavy metals may cause both acute and chronic poisoning related to the pollution of the natural environment (water, soil, air) and/or work environments (occupational exposure). The entry into the human body of metals such as lead, mercury, or cadmium (one of the main environmental xenobiotics harmful to animals and humans, exposure to which is constantly increasing, constituting a significant public health problem in industrialized countries), even in small amounts, can pose a serious threat to human health and life. These metals are very toxic. They accumulate in the organism, especially in the liver and kidneys, causing damage. In addition, they may adversely affect the nervous, skeletal, and cardiovascular systems and also lead to the development of cancer.

Some elements, despite their multidirectional biological activity, can be toxic at high concentrations, generate free radicals, and lead to the intensification of lipid peroxidation, i.e., a free radical process that underlies one of the mechanisms of cell damage. One such element is vanadium, which is widely used in many industries, leading to constantly increasing environmental pollution from this metal. It should be emphasized that the results of certain studies into the role of vanadium in, for example, neurodegenerative processes, indicate that this element, contained in PM2.5 particles, may adversely affect the nervous system and contribute to the development of disorders such as Alzheimer and Parkinson diseases.

Biologically active compounds of plant origin constitute a very large group of substances that can have a beneficial effect on the human organism. They occur in leaves, fruits, and seeds, among other plant elements. It has been shown that biologically active compounds can play an important role in the prevention and treatment of some lifestyle diseases. Moreover, their antiviral, antibacterial, antifungal, and anti-inflammatory effects have been demonstrated. Some of them can also scavenge free radicals.

It should be highlighted that, for a long time, there has been high interest in biologically active compounds of plant origin in terms of their potential in preventing the toxic effects of metals. This is a very important and currently relevant trend associated with the search for effective strategies based on substances of natural origin to prevent the toxic effects of xenobiotics or mitigate the effects of their actions. Moreover, metal complexes, due to their pharmacological potential, have also been drawing interest. Their structures and properties make them therapeutically effective.

We invite authors to submit original research papers or review articles on the pharmacological activity of metal-containing complexes and compounds such as polyoxometalates and on links between metal coordination compounds and potential therapies for human pathologies with mechanistic analysis. We also invite authors to submit original research papers or review articles on biologically active compounds of plant origin in the treatment of modern-age diseases and the prevention of health risks related to metal exposure.

Potential topics include, but are not limited to, the following:

  • Plant-derived compounds/plant extracts;
  • Metal complexes (also complexed with plant-derived compounds) and polyoxometalates;
  • Metal toxicity;
  • Therapeutic bioactive molecules;
  • Pharmacological potential of metal complexes (including plant-derived compounds) and polyoxometalates;
  • Lifestyle disorders;
  • Mechanisms.

Dr. Agnieszka Scibior
Prof. Dr. Juan Llopis
Dr. Manuel Aureliano
Guest Editors

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Keywords

  • bioactive compounds
  • metals
  • metal complexes
  • polyoxometalates
  • modern-age diseases
  • toxicity
  • therapeutic importance
  • novel applications

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Published Papers (3 papers)

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Research

18 pages, 2901 KiB  
Article
Protective Action of Cannabidiol on Tiamulin Toxicity in Humans—In Vitro Study
by Eryka Pankowska, Oliwia Kończak, Paula Żakowicz, Tatiana Wojciechowicz, Maciej Gogulski and Lidia Radko
Int. J. Mol. Sci. 2024, 25(24), 13542; https://doi.org/10.3390/ijms252413542 - 18 Dec 2024
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Abstract
The growing awareness and need to protect public health, including food safety, require a thorough study of the mechanism of action of veterinary drugs in consumers to reduce their negative impact on humans. Inappropriate use of veterinary drugs in animal husbandry, such as [...] Read more.
The growing awareness and need to protect public health, including food safety, require a thorough study of the mechanism of action of veterinary drugs in consumers to reduce their negative impact on humans. Inappropriate use of veterinary drugs in animal husbandry, such as tiamulin, leads to the appearance of residues in edible animal tissues. The use of natural substances of plant origin, extracted from hemp (Cannabis sativa L.), such as cannabidiol (CBD), is one of the solutions to minimize the negative effects of tiamulin. This study aimed to determine the effect of CBD on the cytotoxicity of tiamulin in humans. The cytotoxic activity of tiamulin and the effect of its mixtures with CBD were tested after 72 h exposure to three human cell lines: SH-SY5Y, HepG2 and HEK-293. Cytotoxic concentrations (IC50) of the tested drug and in combination with CBD were assessed using five biochemical endpoints: mitochondrial and lysosomal activity, proliferation, cell membrane integrity and effects on DNA synthesis. Oxidative stress, cell death and cellular morphology were also assessed. The nature of the interaction between the veterinary drug and CBD was assessed using the combination index. The long-term effect of tiamulin inhibited lysosomal (SH-SY5SY) and mitochondrial (HepG2) activity and DNA synthesis (HEK-293). IC50 values for tiamulin ranged from 2.1 to >200 µg/mL (SH-SY5SY), 13.9 to 39.5 µg/mL (HepG2) and 8.5 to 76.9 µg/mL (HEK-293). IC50 values for the drug/CBD mixtures were higher. Reduced levels of oxidative stress, apoptosis and changes in cell morphology were demonstrated after exposure to the mixtures. Interactions between the veterinary drug and CBD showed a concentration-dependent nature of tiamulin in cell culture, ranging from antagonistic (low concentrations) to synergistic effects at high drug concentrations. The increased risk to human health associated with the presence of the veterinary drug in food products and the protective nature of CBD use underline the importance of these studies in food toxicology and require further investigation. Full article
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14 pages, 8177 KiB  
Article
The Protective Role of Intermedin in Contrast-Induced Acute Kidney Injury: Enhancing Peritubular Capillary Endothelial Cell Adhesion and Integrity Through the cAMP/Rac1 Pathway
by Tingting Gao, Ruiyuan Gu, Heng Wang, Lizheng Li, Bojin Zhang, Jie Hu, Qinqin Tian, Runze Chang, Ruijing Zhang, Guoping Zheng and Honglin Dong
Int. J. Mol. Sci. 2024, 25(20), 11110; https://doi.org/10.3390/ijms252011110 - 16 Oct 2024
Viewed by 872
Abstract
Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of [...] Read more.
Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of IMD in CIAKI, focusing on its mechanisms, particularly the cAMP/Rac1 signaling pathway. Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were assessed using CCK8 assay, flow cytometry, ELISA, and Western blotting. A CIAKI rat model was utilized to evaluate renal peritubular capillary endothelial cell injury and renal function through histopathology, immunohistochemistry, immunofluorescence, Western blotting, and transmission electron microscopy. In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway, with Rac1 inhibition attenuating these protective effects. In vivo, CIAKI caused severe damage to peritubular capillary endothelial cell junctions, impairing renal function. IMD treatment markedly improved renal function, an effect negated by Rac1 inhibition. IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, preserving peritubular capillary endothelial integrity and alleviating acute renal injury from contrast media. These findings suggest that IMD has therapeutic potential in CIAKI and highlight the cAMP/Rac1 pathway as a promising target for preventing contrast-induced acute kidney injury in at-risk patients, ultimately improving clinical outcomes. Full article
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31 pages, 4974 KiB  
Article
The Protective Effect of the Supplementation with an Extract from Aronia melanocarpa L. Berries against Cadmium-Induced Changes of Chosen Biomarkers of Neurotoxicity in the Brain—A Study in a Rat Model of Current Lifetime Human Exposure to This Toxic Heavy Metal
by Agnieszka Ruczaj, Joanna Rogalska, Małgorzata Gałażyn-Sidorczuk and Małgorzata M. Brzóska
Int. J. Mol. Sci. 2024, 25(20), 10887; https://doi.org/10.3390/ijms252010887 - 10 Oct 2024
Viewed by 824
Abstract
Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find [...] Read more.
Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3–24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy. Full article
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