JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY

Impact of preeclampsia on mineral status in rats
Suliburska J and Cholik R
This study aimed to assess the influence of preeclampsia on mineral homeostasis in a rat model of preeclampsia. Twelve-week-old female pregnant Sprague Dawley rats were divided into two groups: healthy rats (CH, n = 6) and preeclamptic rats (CP, n = 6). The rat model of preeclampsia was induced by NG-nitro-Larginine-methyl-ester (L-NAME). Blood pressure (systolic (SBP) and diastolic (DBP)) was measured at 18 gestational days (GD) using a non-invasive blood pressure system CODA (Kent Scientific). At 19 GD final body mass was measured then rats were euthanised by decapitation and tissues and blood samples were collected. Body mass, relative tissue mass (% of body mass), fetus, and placenta mass were measured. Morphological and biochemical parameters were assayed in blood in the certified diagnostic laboratory. Calcium (Ca), magnesium (Mg, iron (Fe), zinc (Zn) and copper (Cu) content in tissues were determined using flame atomic spectrometry (ZA 3000 Hitachi) after mineralization in a Microwave Digestion system (Mars 2™ System). Statistical analysis was performed using GraphPad Prism. The systolic blood pressure was significantly higher in preeclamptic rats compared to the healthy group. The relative mass of the liver was markedly lower in the CP group than in the CH group. The ratio between platelets and lymphocytes, and neutrophils and lymphocytes were significantly higher in preeclamptic rats than in the control group. L-NAME treatment significantly increased Ca concentration in placenta and kidney and markedly decreased content of Cain liver. Mg content in kidney was significant higher and Cu concentration in fetus was significantly lower in CP than in CH group. The significant positive correlations were found between SBP and Ca content in placenta and kidney (respectively). The reverse correlations between Ca concentration in liver and SBP and between Cu content in fetus and SBP was observed. Correlations were found between the content of elements in tissues and morphological parameters reflecting inflammation and hypoxia. In conclusion, preeclampsia may disturb minerals content in maternal and fetal tissues in rats. Changes in mineral status in preeclampsia may be related to inflammation and hypoxia. It seems that Ca may play a role in regulating systolic blood pressure in preeclamptic rats.
Establishing a baseline for environmental risk assessment: a systematic review of the disposal of mining tailings in the crossborder region Romania - Serbia
Nemeş NS, Kržanović D, Stojanović M, Negrea A, Negrea P and Muntean C
The cross-border region between Romania and Serbia has been deeply affected by decades of mining activities, resulting in significant environmental degradation and public health risks. By consolidating data from peer-reviewed studies, government reports, and environmental monitoring datasets, this systematic review and quantitative synthesis establish a critical basis for the environmental risk assessment from mining activities as a result of tailings storage in the Romania-Serbia cross-border area, with a focus on the Moldova Nouă (Romania) and Bor (Serbia) mining areas. Following PRISMA 2020 methodology, 22 studies were systematically identified and included in the quantitative synthesis. The review identifies the main routes of contamination, quantifies the levels of pollutants such as heavy metals (copper, lead, zinc, arsenic) and assesses the socio-economic impact, providing a framework for setting a baseline for future monitoring and remediation strategies. Statistical re-analysis of aggregated data indicated severe pollution for lead in Moldova Nouă (Geoaccumulation Index, Igeo = 4.32, "strong to extremely polluted") and significant arsenic contamination in Bor (Igeo ≈ 3.5). Copper showed moderate pollution (Igeo ≈ 2.4) in Moldova Nouă. The proposed baseline, adopted from Romanian national standards (Order 756/1997), includes soil metal concentration thresholds (Cu: 20 mg/kg d.w., Pb: 50 mg/kg d.w.), a Water Quality Index (WQI) below 50 (indicating good quality), and an occupational morbidity rate below 5 cases per 1000 workers. The results highlight the urgent need for bilateral cooperation to manage crossborder pollution and reduce occupational morbidity through integrated interventions.
Selenium status and supplementation in thyroid disorders: A narrative review of current evidence
Linn YH, Aziz S and Mok SL
Selenium (Se), an essential trace element, plays a pivotal role in thyroid hormone synthesis and antioxidant defence mechanisms. This narrative review comprehensively examines the current evidence on Se status and supplementation in various thyroid disorders. Numerous studies indicate that Se deficiency may contribute to the development and progression of thyroid diseases, particularly autoimmune conditions such as Graves' disease (GD), Graves' orbitopathy (GO), and autoimmune thyroiditis (AIT), including Hashimoto's thyroiditis (HT). In GD and GO, Se supplementation, especially when combined with methimazole, has been shown to enhance hormone normalization and antioxidant capacity, although results vary across studies. In AIT and HT, consistent reductions in thyroid autoantibodies and inflammatory markers have been observed following Se supplementation, particularly with selenomethionine. However, the evidence remains inconsistent regarding Se's impact on hypothyroidism, pregnancy-related thyroid dysfunction, goitre, and thyroid cancer. Supplementation of Se has been associated with improvements in quality of life in some thyroid disorders such as GD, GO and HT with subclinical hypothyroidism. While some studies suggest a potential protective or modulatory role, findings vary by geographic region, baseline Se status, and study designs. Excessive intake of Se may also carry risks of toxicity (selenosis) and should be approached with caution. In conclusion, Se supplementation offers potential therapeutic benefits, particularly in autoimmune thyroid diseases. However, further well-designed randomized-controlled trials are necessary to define the optimal form, dose, and duration of supplementation and to clarify its role across diverse thyroid conditions.
Alleviating stocking density stress in juvenile rainbow trout (Oncorhynchus mykiss) through dietary nano-selenium: Effects on growth, antioxidant activity, and immune response
Ali M, Akram A, Jan FA, Ahmad A, Hussain A, Khan FU and Arshad M
Trout is a prized fish mostly cultured under high stocking densities (SD), which relates to many physiological challenges. The present study determines the significance of nano selenium (Se-N), while rearing Rainbow trout (Oncorhynchus mykiss) under various SD. Healthy O. mykiss juvenile were randomly distributed in concrete raceways in a 4 × 5 factorial experimental design. Five experimental feeds (NS0, NS1, NS2, NS3, NS4) containing 0, 1, 2, 3, and 4 mg Se-N per Kg were tested in four SDs (SD-L=168, SD-M=300, SD-H=433, SD-V=567 g/m). Inference revealed significant effects of both SD and Se-N on growth (NWG), antioxidant activity and molecular regulation of myogenesis, and immunity. Our results show no significant effect of SD on growth at SD-L and SD-M, however at higher SD (SD-H and SD-V) Se-N role became prominent as significantly high NWG was observed in NS3 followed by NS2, NS4, NS1 and NS0, respectively. Lower cortisol in NS3 at higher SD might be the result of higher antioxidant activity (SOD, CAT, GPx), which seems to counter the chronic stress caused by SD. High SD also induced expression of immunity related genes (Lysozyme and IL-1β) especially in absence/lower inclusion of Se-N, while upregulated hsp70 expression. Finally, the dose dependent (Se-N) high expression of MyoD and gh, and a very slight effect on igf-1 justify the higher growth in NS3 by hyperplasia and not by hypertrophy. Our study suggests supplementation of 3 mg/kg Se-N in the diet of O. mykiss, especially in culture condition of high SD.
Therapeutic effects of a new selenium-sorafenib nanocomplex in liver and tumor in a TAA-induced HCC model
Varlamova EG, Gudkov SV, Rogachev VV and Turovsky EA
The objective of this work was to develop and study the therapeutic properties of a nanocomplex based on selenium nanoparticles, an important microelement, and sorafenib, a known anticancer drug, on a model of hepatocellular carcinoma in mice. This nanocomplex combines the anticancer activity of selenium and sorafenib, which significantly increases its effectiveness in the treatment of HCC METHODS: A nanocomplex of selenium and sorafenib (SeSo) was obtained by laser ablation. To test the physicochemical properties of the nanocomplex, absorption spectrometry, dynamic light scattering, fluorimetry and electron microscopy were used. In the course of the work, real-time PCR was used to screen the mRNA expression levels of more than 40 genes encoding key markers of various signaling cascades associated with HCC, separately in the liver and tumor. Western blotting was used to test the reliability of real-time PCR. To assess the tumor size and the liver size and weight of mice, morphometric and statistical analyses were used.
The therapeutic effect of zinc oxide nanoparticles against lipopolysaccharides on the rats' retina
Emara EM, El-Sayyad HI, Mowafy AM and El-Ghaweet HA
Lipopolysaccharide (LPS), a potent endotoxin, triggers oxidative stress and inflammatory cascades that contribute to retinal degeneration and disruption of the gut-retina axis. Zinc oxide nanoparticles (ZnO NPs) have emerged as promising agents owing to their strong antioxidant and anti-inflammatory activities, yet their role in retinal protection remains underexplored.
Selective impact of zinc on human circulating CD56 NK cells
Bennstein SB, Stöcker R, Heenen L, Jakobs J, Ohl K and Rink L
Natural Killer (NK) cells are essential for recognizing aberrant and virus-infected cells. Adequate levels of the trace element zinc are known to be important for proper immune functionality against infections and tumor growth. So far, not many studies have analyzed the effects of zinc on NK cells. We previously observed higher levels of activated CD69 NK cells in zinc-adequate compared to zinc-deficient donors. We therefore aimed to analyze the influence of zinc on the activation and functionality of NK cell in vitro.
Serum trace element and mineral levels and fecal microbiota in relation to cartilage damage in rheumatoid arthritis patients
Skalny AV, Korobeinikova TV, Morozova G, Menshikova IV, Gritsenko VA, Zhang F, Mak DV, Guo X, Sotnikova TI, Aschner M and Tinkov AA
The objective of the present study was to evaluate serum trace element and mineral levels as well as taxonomic characteristics of gut microbiota and their association with cartilage damage in patients with rheumatoid arthritis (RA).
Impact of hidden hunger on pregnant women from underserved communities and its role in anaemia
Pathak AK, Agarwal D, Singh S, Kulshresthra R, Raj Kulshrestha M and Tiwari V
Micronutrient deficiencies (MiNDs) during pregnancy contribute to anemia, preeclampsia, and poor fetal outcomes. We assessed the prevalence of MiNDs and their association with anemia among pregnant women in northern India.
Azelastine attenuates Cisplatin-induced renal and testicular injury: Involvement of Nrf2/SLC7A11-GPX4 and NCOA4-mediated ferroptosis
El-Ela SRA, El Gayar AM and Zaghloul RA
Renal and testicular toxicities are side effects of the chemotherapeutic agent cisplatin (Cis). The study aims to assess the potential repurpose of Azelastine (Az), an H1-receptor antagonist to alleviate Cis-induced toxicity.
Associations between cadmium and lead exposure and thyroid disorders: A systematic review and meta-analysis
Abdelgawwad El-Sehrawy AAM, Hsu CY, Saleh EAM, Moharam MM, Rekha MM, Kundlas M, Premkumar J, Ray S, Hussein AR and Kadhim MA
Exposure to heavy metals, specifically Cadmium and lead, poses considerable public health risks, as these substances are known endocrine disruptors that can negatively influence the regulation of thyroid hormones. This systematic review and meta-analysis examine the associations between cadmium and lead exposure and thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroid cancer. The study was conducted by searching PubMed, Scopus, Embase, Web of Science, and Google Scholar, identifying 23,333 studies. After removing duplicates, 4980 were excluded for reasons such as being reviews, non-English, or unrelated, and after assessing full-text, 21 studies were included for qualitative and quantitative analysis. A random-effects meta-analysis was conducted to estimate pooled odds ratios (95 % CI) for the association between heavy metal exposure and thyroid disorders, with heterogeneity assessed via the I² statistic. Meta-analysis confirmed significant associations between both metals and thyroid disorders. Lead exposure showed a strong relationship (pooled OR ≈ 2.7), while cadmium also demonstrated a meaningful association (pooled OR ≈ 1.6), though with moderate heterogeneity across studies, suggesting variations due to study design, exposure assessment, or demographic factors. These findings emphasize the public health importance of reducing exposure, as both metals possess endocrine-disrupting potential. Mechanistically, cadmium appears to act through oxidative and hormonal pathways, whereas lead shows stronger associations with thyroid cancer and autoimmunity, particularly in occupational settings. Limited evidence further indicates possible sex-related and gene-environment interactions. The evidence reviewed indicates that cadmium and lead may contribute to the development of thyroid disorders through various biological pathways.
METTL14 promotes ferroptosis during the development of cisplatin-induced kidney injury by stabilizing ERFE through IGF2BP3-dependent mA methylation
Chen Y, Li W, Zhao D, Huang C and Xu C
Cisplatin-induced acute kidney injury (CP-AKI) is a major complication of cisplatin chemotherapy that is mechanistically linked to ferroptosis, an iron-dependent form of cell death. However, the epigenetic and post-transcriptional factors regulating ferroptosis in CP-AKI, particularly those mediated by N6-methyladenosine (mA) RNA methylation, remain insufficiently defined. This study investigated the role of methyltransferase-like 14 (METTL14)-mediated mA RNA methylation and its downstream targets in ferroptosis regulation during CP-AKI.
TCF19 up-regulated in hypoxic lung cancer cells attenuates the anti-tumor effects of sodium selenite
Li S, Tian W, Han K, Zhang Y, Wang Y and Shi K
Hypoxia existing inside tumor tissues stimulates proliferation, metastasis and drug resistance of lung cancer. Selenite, an inorganic form of selenium, has been widely confirmed to induce apoptosis of multiple kinds of tumors. However, its therapeutic effects on hypoxic lung cancer were still unclear.
Anticancer activity of the new manganese(II), iron(II), nickel(II), copper(II), and zinc(II) complexes based on 1,2,4-triazoline-3-thione derivative
Czylkowska A, Lanka S, Rogalewicz B, Raducka A, Fornal E, Iwan M, Kubik J, Korga-Plewko A, Humeniuk E, Świątkowski M, Pitucha M, Gajda A, Lis A, Szymański P, Smoluch M, Żarczyński A, Drabińska A, Camargo BC and Szczytko J
In this study, we report the anticancer evaluation, synthesis, and characterization of a novel organic ligand, 4-butyl-5-((1-methyl-1H-pyrrol-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and its five metal complexes based on Mn(II), Fe(II), Ni(II), Cu(II), and Zn(II) ions. All compounds were analyzed using elemental analysis, NMR and FTIR spectroscopies, magnetic measurements, ESR, and thermogravimetric analysis. Their antioxidant properties were evaluated using the ABTS and DPPH assays, and the anticancer activity was studied in silico via molecular docking and in vitro against a panel of cancer cell lines. Notably, the Fe(II), Ni(II), and Cu(II) complexes exhibited potent anticancer activity, with IC values of 40.66, 45.95, and 26.51 µM against MDA-MB-231 cells. Their mechanism of action was further investigated through gene expression analysis, cell cycle analysis, apoptosis detection, thiol level evaluation, and DNA damage assessment. The results revealed that Ni(II) and Cu(II) complexes are significantly cytotoxic, while the Fe(II) complex acts as a potent cytostatic agent. Importantly, all compounds demonstrated lower activity toward normal cells than the tested cancer cells.
Camel whey protein coated metal-organic frameworks (CWP/MOF) as a sustainable approach to treat environmental stress-induced liver toxicity by cobalt chloride in rats
Hamad D, Dawood AFA, Alharbi HM, Refaie SM, Ali MA, Abu-Sehly AA, Abdel-Tawab HS, Welson NN and Abd El-Aziz FEA
Environmental stressors, such as heavy metal pollution, can have devastating effects on biological organisms, leading to conditions like liver toxicity. This study explored the therapeutic potential of a novel iron-based metal-organic framework (Fe-MOF) in mitigating cobalt chloride-induced liver toxicity in rats.
Environmental trace metals contamination near a copper mining area from central-west region of Romania
Morariu FE, Zoican EC, Horablaga MN, Popa NF, Cristina RT, Dumitrescu E, Grigorescu CC, Horablaga A and Morariu S
The rising global demand for metals has intensified mining operations, resulting in considerable environmental pollution by heavy metals in soils and water bodies, which endangers ecosystems and human health. While heavy metals are naturally present in soils and aquatic environments, human activities such as mining and smelting have significantly disrupted their biogeochemical cycles, causing increased concentrations that pose threats to both the environment and public health. This study focuses on assessing the levels of trace and heavy metals in river water and soils in a Romanian copper mining region, as well as examining their bioaccumulation in soils, aquatic organisms, and plants. The findings aim to provide essential data to support environmental management and remediation efforts.
Genotoxic and oxidative stress assessment of heavy metal contaminated soil and water in human blood and bovine milk samples from the different industrial zones of Punjab, Pakistan
Ali MM, Awan F, Jamil MU, Ijaz M, Ullah A and Shehzad W
This study investigates the genotoxic effects and oxidative stress of heavy metal contaminated soil and water on human and bovine blood, as well as bovine milk samples, from industrial zones of Punjab, Pakistan. Samples were collected from Multan, Lahore, Gujranwala, Bahawalpur and Faisalabad and analyzed through Atomic Absorption Spectrophotometry (AAS) for heavy metal analysis. Heavy metals such as lead (Pb), chromium (Cr), arsenic (As), zinc (Zn), cadmium (Cd), copper (Cu), molybdenum (Mo), iron (Fe), mercury (Hg), and nickel (Ni) were identified. The highest levels were found in district Faisalabad across water, soil, bovine, and human samples whereas, Gujranwala showed the lowest concentrations except for Pb and Cr in water and Hg in human plasma samples (P < 0.05). Additionally, Principal Component Analysis (PCA) highlighted that Faisalabad had the highest burden of Ni, Cu and Zn followed by Lahore with significantly higher levels of Pb and Cr. Among all districts, human and bovine blood and bovine milk samples displayed the highest amount of DNA damage via comet assay, while lowest levels were seen in these samples belonging to Bahawalpur (P < 0.05). Human and bovine blood samples from Faisalabad showed elevated Total Oxidant Status (TOS) along with reduced Total Antioxidant Status (TAS) (P < 0.05), whereas blood samples from Bahawalpur exhibited the lowest TOS and TAS levels (P < 0.05). Moreover, human and bovine blood samples from Faisalabad exhibited a significant upregulation of caspase-3 compared to other districts (P < 0.05). The study concluded that industrialization in Punjab results in significant heavy metal contamination, causing genotoxicity and oxidative stress in livestock and humans.
Gallic acid mitigates cadmium-induced reproductive damage: Effects on sperm, antioxidants, and apoptosis in mice
Alaee S, Derakhshan Z, Koohpeyma F, Shokri S, Talaie A and Kamyab H
Cadmium is a well-known reproductive toxicant found in many industrial wastes. The gallic acid impact on the recovery of reproductive ability of mice exposed to cadmium was investigated. The experiment involved six groups of male mice, designated as Groups 1 through 6, each receiving specific treatments: Group 1 received distilled water, Group 2 received water containing gallic acid with a concentration of 50 mg/kg, Group 3 received water containing gallic acid with a concentration 100 mg/kg, Group 4 was treated with water containing cadmium with a concentration of 1.2 mg/kg, Group 5 received water containing cadmium and gallic acid with concentrations of 1.2 mg/kg and 50 mg/kg, respectively, and finally Group 6 received water containing 1.2 and 100 mg/kg of cadmium and gallic acid, respectively. The mice's blood samples were collected after finishing the treatment stage to evaluate testosterone levels, and the testes were excised for stereological analysis and assessment of antioxidant and apoptotic marker expression. Sperm samples extracted from the epididymis were analyzed for quantity, morphology, motility, viability, maturation, and DNA fragmentation. Results indicated significant declines in all measured parameters in mice exposed to cadmium. Additionally, high doses of gallic acid adversely affected some fertility parameters in normal mice. In cadmium-exposed mice, mRNA expression of antioxidants (Gpx1, Cat, and Sod1) and anti-apoptotic (Bcl2l1) genes was significantly reduced, while the expression of proapoptotic (Caspase3 and Bax) genes increased. Notably, 50 mg/kg of gallic acid improved all fertility parameters in these mice. It is suggested that the high concentration of antioxidants can control oxidative stress, thereby disrupting the normal physiological level of reactive oxygen species in the mice's cells. Therefore, gallic acid at the appropriate dose improves fertility parameters in mice exposed to cadmium. The results showed that the dose of 50 mg/kg of gallic acid can effectively mitigate the cadmium detrimental impacts on the health of the vital organs of the male mice reproductive system. These findings suggest the potential therapeutic application of gallic acid in combating reproductive toxicity induced by cadmium, highlighting the importance of dosage in achieving beneficial outcomes.
Response to Letter to the editor: Sex difference in the association between dietary iron intake and bone mineral density in adolescents aged 12-19: A cross-sectional study
Li K, Han J, Zhu J, Zhu X, Zhong Y and Zhu Z
Molybdenum induces hepatic impairments via dysregulating NLRP3, JAK1/STAT3 and NF-κB pathways: A dose dependent toxicity assessment
El Safadi M, Alkhoshaiban AS, Hayat MF, Zahara SS, Akbar A, Al-Aream MA, Jamil S and Hassan HM
Molybdenum (Mo) is an important trace element that is documented to instigate several toxicities in different organs of the body. Mo demonstrates adverse effects by inducing oxidative stress (OS), inflammatory damage as well as apoptotic responses in key regulatory organs of the body.
Serum copper-zinc and copper-selenium ratios in relation to bone health among U.S. adolescents
Shen Y, Liu H, Shangguan Y, Li Q, Yu X, Tang H and Lin X
Adolescence is a critical window for bone development, during which trace elements like copper, zinc, and selenium play essential roles. While previous studies have focused on individual elements, trace element ratios such as the copper-zinc and copper-selenium ratios may better capture biological interactions relevant to bone health.