Pub Date : 2025-10-01DOI: 10.1016/j.jtemb.2025.127771
Jeongwon Ock , Choong-Hee Park , Yoon-Hyeong Choi
Background
Obesity in adults has substantially increased, and the proportion of obese adults worldwide is estimated to exceed 50 % by 2030.
Objective
This study aims to evaluate the association between heavy metal exposure and obesity in the general adult population in Korea.
Methods
We used data from 14832 general adults from the Korean National Environmental Health Survey (KoNEHS) 2009–2017 with measures of heavy metals in blood and urine samples. Survey linear regression or survey logistic regression models were performed to assess the associations of blood lead, cadmium, and mercury, and urine arsenic and manganese with body mass index or obesity.
Results
After adjustment for confounders, participants in the highest quintile of blood lead and mercury had significantly higher odds of obesity compared to those in the lowest quintile (OR: 1.22 (95 % CI: 1.07–1.44); 2.17 (95 % CI: 1.87–2.51)) with dose-response relationships (both P for trend < 0.001). For blood manganese, participants in the third quintile had significantly higher odds of obesity (1.33 (95 % CI: 1.06–1.67)). There was a marginally significant increase in odds of underweight among those in the third quintile of urine arsenic compared to those in the lowest quintile (1.43 (95 % CI: 0.77–2.66)). There was no association between the quintiles of urine cadmium and arsenic levels and obesity.
Conclusion
We provide evidence of a dose-response association between lead and mercury exposure and an increased risk of obesity in Korean adults. Exposure to manganese at moderate concentrations was associated with obesity. In addition, exposure to arsenic was marginally associated with an increased risk of underweight. Additional prospective studies are required to elucidate the effects of heavy metals on obesity.
{"title":"Environmental exposures to lead, mercury, cadmium, manganese, and arsenic and obesity in Korean adults: Korean National Environmental Health Survey 2009–2017","authors":"Jeongwon Ock , Choong-Hee Park , Yoon-Hyeong Choi","doi":"10.1016/j.jtemb.2025.127771","DOIUrl":"10.1016/j.jtemb.2025.127771","url":null,"abstract":"<div><h3>Background</h3><div>Obesity in adults has substantially increased, and the proportion of obese adults worldwide is estimated to exceed 50 % by 2030.</div></div><div><h3>Objective</h3><div>This study aims to evaluate the association between heavy metal exposure and obesity in the general adult population in Korea.</div></div><div><h3>Methods</h3><div>We used data from 14832 general adults from the Korean National Environmental Health Survey (KoNEHS) 2009–2017 with measures of heavy metals in blood and urine samples. Survey linear regression or survey logistic regression models were performed to assess the associations of blood lead, cadmium, and mercury, and urine arsenic and manganese with body mass index or obesity.</div></div><div><h3>Results</h3><div>After adjustment for confounders, participants in the highest quintile of blood lead and mercury had significantly higher odds of obesity compared to those in the lowest quintile (OR: 1.22 (95 % CI: 1.07–1.44); 2.17 (95 % CI: 1.87–2.51)) with dose-response relationships (both <em>P</em> for trend < 0.001). For blood manganese, participants in the third quintile had significantly higher odds of obesity (1.33 (95 % CI: 1.06–1.67)). There was a marginally significant increase in odds of underweight among those in the third quintile of urine arsenic compared to those in the lowest quintile (1.43 (95 % CI: 0.77–2.66)). There was no association between the quintiles of urine cadmium and arsenic levels and obesity.</div></div><div><h3>Conclusion</h3><div>We provide evidence of a dose-response association between lead and mercury exposure and an increased risk of obesity in Korean adults. Exposure to manganese at moderate concentrations was associated with obesity. In addition, exposure to arsenic was marginally associated with an increased risk of underweight. Additional prospective studies are required to elucidate the effects of heavy metals on obesity.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127771"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-29DOI: 10.1016/j.jtemb.2025.127770
Kalimuthu Kalishwaralal , Prajakta Patil , Aniket Mali
Objective
Ferroptosis is an iron-dependent, non-apoptotic form of metabolic cell death driven by lipid peroxidation. While Glutathione Peroxidase 4 (GPX4) is the canonical ferroptosis suppressor, recent evidence highlights additional selenoproteins, including Thioredoxin Reductase 1 (TXNRD1) and Peroxiredoxin 6 (PRDX6), as critical modulators of ferroptotic sensitivity. We compared three mechanistically distinct ferroptosis inducers, RSL3 (a covalent GPX4 inhibitor), auranofin (a TXNRD1 inhibitor), and artesunate (ART; a pro-oxidant derivative of artemisinin), in MDA-MB231, A549 and HepG2 cell lines.
Method
Cell viability (MTT) and wound-healing assays quantified cytotoxic and anti-migratory effects. Our inhibitor study using Ferrostatin-1(Ferro) and Liproxstatin-1(Lipo), in combination with ferroptosis inducers, confirmed the specificity of ferroptosis. Beyond GPX4, TXNRD1 and PRDX6 constitute a complementary selenium-dependent axis safeguarding cancer cells from ferroptosis. Dual targeting of GPX4 and TXNRD1, or disruption of PRDX6-mediated selenium trafficking, potentiates ferroptosis death and impedes metastatic traits.
Results
Using in silico methods, we confirmed the interaction between drug and protein molecules. Among the tested compounds, RSL3 and auranofin exhibited strong binding affinity towards all the targeted proteins, including GPX4, TXNRD1, and PRDX6, suggesting their potential as effective ferroptosis pathway inhibitors.
Conclusions
These findings nominate multi-selenoproteins inhibition as a promising strategy to overcome ferroptosis resistance.
{"title":"Ferroptosis-targeting compounds modulate cancer cell cytotoxicity and migration: Insights from in vitro and in silico analyses","authors":"Kalimuthu Kalishwaralal , Prajakta Patil , Aniket Mali","doi":"10.1016/j.jtemb.2025.127770","DOIUrl":"10.1016/j.jtemb.2025.127770","url":null,"abstract":"<div><h3>Objective</h3><div>Ferroptosis is an iron-dependent, non-apoptotic form of metabolic cell death driven by lipid peroxidation. While Glutathione Peroxidase 4 (GPX4) is the canonical ferroptosis suppressor, recent evidence highlights additional selenoproteins, including Thioredoxin Reductase 1 (TXNRD1) and Peroxiredoxin 6 (PRDX6), as critical modulators of ferroptotic sensitivity. We compared three mechanistically distinct ferroptosis inducers, RSL3 (a covalent GPX4 inhibitor), auranofin (a TXNRD1 inhibitor), and artesunate (ART; a pro-oxidant derivative of artemisinin), in MDA-MB231, A549 and HepG2 cell lines.</div></div><div><h3>Method</h3><div>Cell viability (MTT) and wound-healing assays quantified cytotoxic and anti-migratory effects. Our inhibitor study using Ferrostatin-1(Ferro) and Liproxstatin-1(Lipo), in combination with ferroptosis inducers, confirmed the specificity of ferroptosis. Beyond GPX4, TXNRD1 and PRDX6 constitute a complementary selenium-dependent axis safeguarding cancer cells from ferroptosis. Dual targeting of GPX4 and TXNRD1, or disruption of PRDX6-mediated selenium trafficking, potentiates ferroptosis death and impedes metastatic traits.</div></div><div><h3>Results</h3><div>Using <em>in silico</em> methods, we confirmed the interaction between drug and protein molecules. Among the tested compounds, RSL3 and auranofin exhibited strong binding affinity towards all the targeted proteins, including GPX4, TXNRD1, and PRDX6, suggesting their potential as effective ferroptosis pathway inhibitors.</div></div><div><h3>Conclusions</h3><div>These findings nominate multi-selenoproteins inhibition as a promising strategy to overcome ferroptosis resistance.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127770"},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.jtemb.2025.127772
Parameswari R. , Jesu Jaya Sudan R. , Lesitha Jeeva Kumari J. , Madhan Kumar P. , Babujanarthanam R.
<div><h3>Background</h3><div>Essential Elements (EEs) such as calcium, zinc, selenium, magnesium, copper, sodium, and potassium are essential for spermatogenesis. They maintain seminal proteins, especially semenogelin and sperm morphology, which are followed by spermatozoa ejaculation to reach the egg for successful conception. In addition, these elements serve as nutrients/cofactors during ejaculation and enhance spermatogenic rapid progressive motility with sustained sperm integrity.</div></div><div><h3>Aim</h3><div>The current study sought to determine the relationship of essential elements (calcium, zinc, selenium, magnesium, copper, sodium, and potassium) between these three major components of sperm morphology, quality, and integrity via seminal proteins, as an <em>in vitro</em> and <em>in silico</em> study.</div></div><div><h3>Methodology</h3><div>With appropriate institutional approval, 116 individuals aged 25–39 were divided into normozoospermic (N = 58) and teratozoospermic (N = 58). The study volunteers were selected based on their andrology profile using Computer-Assisted Semen Analysis. This was followed by an atomic absorption spectrometer for essential element quantification, Enzyme Linked Immune Sorbent Assay (ELISA) for testosterone measurement, lipid peroxidation by malondialdehyde (MDA) analysis, sperm chromatin structure assay (SCSA) and acridine orange (AO) staining procedures were used for sperm DNA fragmentation index (DFI). In addition, computational analysis was done to predict ion binding sites on the seminal protein semenogelin.</div></div><div><h3>Results</h3><div>Our results showed the concentration of essential elements to be comparatively lower in teratozoospermic subjects than in normozoospermic (zinc> calcium >magnesium> selenium) individuals with a significant (p < 0.001 &p < 0.05) correlation. Morphological analysis revealed that teratozoospermia subjects have sperms with altered morphology, directly correlated (p < 0.001& p < 0.05) with reduced zinc, calcium, and selenium due to fragmented DNA and reduced motility. The correlation of semen parameters and essential elements revealed a direct impact of these elements on sperm motility, DNA profile, total antioxidant capacity (TAC), and testosterone levels. In addition, <em>an in silico</em> study confirms the presence of metal binding motifs like D-H-D, C-X-C, and G-K-[TS]-T for Zn, Mg, and Se ions in the seminal protein semenogelin in normozoospermic than teratozoospermic.</div></div><div><h3>Conclusion</h3><div>Our study's findings have significant implications for male reproductive health. We propose that the presence and adequate concentration of essential elements, notably zinc, calcium, magnesium, and selenium, are crucial for maintaining sperm morphology. The computational discovery of semenogelin sequences such as D-H-D, C-X-C, and G-K-[TS]-T, which promote robust sperm integrity, further supports this. These findings could gu
{"title":"Deciphering the impact of essential elements on spermatozoa quality and seminal protein integrity- an in vitro and in silico study","authors":"Parameswari R. , Jesu Jaya Sudan R. , Lesitha Jeeva Kumari J. , Madhan Kumar P. , Babujanarthanam R.","doi":"10.1016/j.jtemb.2025.127772","DOIUrl":"10.1016/j.jtemb.2025.127772","url":null,"abstract":"<div><h3>Background</h3><div>Essential Elements (EEs) such as calcium, zinc, selenium, magnesium, copper, sodium, and potassium are essential for spermatogenesis. They maintain seminal proteins, especially semenogelin and sperm morphology, which are followed by spermatozoa ejaculation to reach the egg for successful conception. In addition, these elements serve as nutrients/cofactors during ejaculation and enhance spermatogenic rapid progressive motility with sustained sperm integrity.</div></div><div><h3>Aim</h3><div>The current study sought to determine the relationship of essential elements (calcium, zinc, selenium, magnesium, copper, sodium, and potassium) between these three major components of sperm morphology, quality, and integrity via seminal proteins, as an <em>in vitro</em> and <em>in silico</em> study.</div></div><div><h3>Methodology</h3><div>With appropriate institutional approval, 116 individuals aged 25–39 were divided into normozoospermic (N = 58) and teratozoospermic (N = 58). The study volunteers were selected based on their andrology profile using Computer-Assisted Semen Analysis. This was followed by an atomic absorption spectrometer for essential element quantification, Enzyme Linked Immune Sorbent Assay (ELISA) for testosterone measurement, lipid peroxidation by malondialdehyde (MDA) analysis, sperm chromatin structure assay (SCSA) and acridine orange (AO) staining procedures were used for sperm DNA fragmentation index (DFI). In addition, computational analysis was done to predict ion binding sites on the seminal protein semenogelin.</div></div><div><h3>Results</h3><div>Our results showed the concentration of essential elements to be comparatively lower in teratozoospermic subjects than in normozoospermic (zinc> calcium >magnesium> selenium) individuals with a significant (p < 0.001 &p < 0.05) correlation. Morphological analysis revealed that teratozoospermia subjects have sperms with altered morphology, directly correlated (p < 0.001& p < 0.05) with reduced zinc, calcium, and selenium due to fragmented DNA and reduced motility. The correlation of semen parameters and essential elements revealed a direct impact of these elements on sperm motility, DNA profile, total antioxidant capacity (TAC), and testosterone levels. In addition, <em>an in silico</em> study confirms the presence of metal binding motifs like D-H-D, C-X-C, and G-K-[TS]-T for Zn, Mg, and Se ions in the seminal protein semenogelin in normozoospermic than teratozoospermic.</div></div><div><h3>Conclusion</h3><div>Our study's findings have significant implications for male reproductive health. We propose that the presence and adequate concentration of essential elements, notably zinc, calcium, magnesium, and selenium, are crucial for maintaining sperm morphology. The computational discovery of semenogelin sequences such as D-H-D, C-X-C, and G-K-[TS]-T, which promote robust sperm integrity, further supports this. These findings could gu","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127772"},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iron oxide (α-Fe2O3) nanoparticles (NPs) of different sizes are synthesized using a simple wet chemical method and are used as dietary supplements at rates of zero (control), 1, 2, 3, and 4 g/kg diet throughout the year in Puntius sarana to study its consequences on the growth, haematological parameters, biochemical or blood metabolic parameters, ionoregulatory characteristics, plasma lysozyme activity, antioxidant biomarkers, and fish flesh nutrient composition of the fish. The experiment is designed for bulk and nano iron oxides having particle sizes of 10, 12, 15, and 18 nm. When the concentration of NPs rises to 4 g/kg food and/or the size of the NPs is minimized up to 10 nm, the length, hemoglobin, red blood corpuscle, hematocrit, protein levels, plasma lysozyme, catalase, superoxidase dismutase, and glutathione peroxidase in the blood and crude protein of the fish flesh of P. sarana increase upto 32 cm, 9.73 g/dL, 3.22 million/mm3, 29.19 %, 7.78 g/dL, 0.97 ng/mL, 86.69 ng/mL, 39.81 μmol/min/mg protein, 44.96 U/mL, and 18.59 % respectively; and melanodialdehyde and Crude fat decrease upto 41.71 nmol TBARS/g tissue and 2.90 %, respectively. No significant changes in the values of survival rate, white blood cell, blood glucose, serum glutamic pyruvic transaminase, and serum glutamic oxaloacetic transaminase, sodium, potassium, chloride, crude moisture, and crude ash are observed between the control and treatments. Results indicate that NPs based dietary supplementations provide beneficial conditions of well-being of the fish due to increased absorption of iron in its nano form into the fish body via dietary supplements.
采用简单的湿化学方法合成了不同大小的氧化铁(α-Fe2O3)纳米颗粒(NPs),并在全年中将其作为无(对照)、1、2、3和4 g/kg饲料的膳食补充剂,研究其对鱼的生长、血液学参数、生化或血液代谢参数、离子调节特性、血浆溶菌酶活性、抗氧化生物标志物和鱼肉营养成分的影响。该实验设计用于颗粒尺寸为10、12、15和18 nm的大块和纳米氧化铁。当NPs的浓度上升到4 克/公斤食物和/或NPs是最小的大小10 纳米,长度,血红蛋白,红血细胞比容、蛋白质含量、血浆溶菌酶,过氧化氢酶,superoxidase歧化酶、谷胱甘肽过氧化物酶在鱼的血液和粗蛋白的肉p sarana增加到32 厘米,9.73 g / dL 322万/ mm3 % 29.19,7.78 g / dL 0.97 ng / mL, 86.69 ng / mL, 39.81μ摩尔/分钟/毫克蛋白44.96 U / mL,和分别为18.59 %;黑二醛和粗脂肪分别降低41.71 nmol TBARS/g组织和2.90 %。对照组与处理间存活率、白细胞、血糖、血清谷丙转氨酶、血清谷草转氨酶、钠、钾、氯、粗水分、粗灰分等指标均无显著变化。结果表明,基于NPs的膳食补充剂通过膳食补充剂增加了铁的纳米形式进入鱼类体内的吸收,为鱼类的健康提供了有益的条件。
{"title":"Improvement of well-being and fish fillet nutrient value of a vulnerable minor carp, Puntius sarana (Hamilton, 1822): A result of incorporating Fe trace element in diet through α-Fe2O3 nanoparticles as dietary supplements","authors":"Sampa Mondal , Nilanjana Chatterjee , Baibaswata Bhattacharjee","doi":"10.1016/j.jtemb.2025.127764","DOIUrl":"10.1016/j.jtemb.2025.127764","url":null,"abstract":"<div><div>Iron oxide (α-Fe<sub>2</sub>O<sub>3</sub>) nanoparticles (NPs) of different sizes are synthesized using a simple wet chemical method and are used as dietary supplements at rates of zero (control), 1, 2, 3, and 4 g/kg diet throughout the year in <em>Puntius sarana</em> to study its consequences on the growth, haematological parameters, biochemical or blood metabolic parameters, ionoregulatory characteristics, plasma lysozyme activity, antioxidant biomarkers, and fish flesh nutrient composition of the fish. The experiment is designed for bulk and nano iron oxides having particle sizes of 10, 12, 15, and 18 nm. When the concentration of NPs rises to 4 g/kg food and/or the size of the NPs is minimized up to 10 nm, the length, hemoglobin, red blood corpuscle, hematocrit, protein levels, plasma lysozyme, catalase, superoxidase dismutase, and glutathione peroxidase in the blood and crude protein of the fish flesh of <em>P. sarana</em> increase upto 32 cm, 9.73 g/dL, 3.22 million/mm<sup>3</sup>, 29.19 %, 7.78 g/dL, 0.97 ng/mL, 86.69 ng/mL, 39.81 μmol/min/mg protein, 44.96 U/mL, and 18.59 % respectively; and melanodialdehyde and Crude fat decrease upto 41.71 nmol TBARS/g tissue and 2.90 %, respectively. No significant changes in the values of survival rate, white blood cell, blood glucose, serum glutamic pyruvic transaminase, and serum glutamic oxaloacetic transaminase, sodium, potassium, chloride, crude moisture, and crude ash are observed between the control and treatments. Results indicate that NPs based dietary supplementations provide beneficial conditions of well-being of the fish due to increased absorption of iron in its nano form into the fish body via dietary supplements.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127764"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-26DOI: 10.1016/j.jtemb.2025.127769
Bingyu Wang , Bohan Xing , Luyao Huang , Xiaoyi Li , Xiyun Bian , Jinkun Xi
Background
Zinc is an essential nutrient implicated in cardiovascular health. This study investigates whether Zn2+ protects H9c2 cells by regulating mitochondrial biogenesis, dynamics, and calcium homeostasis via the mitochondrial calcium uniporter (MCU).
Methods
The I/R model were established using simulated ischemia and reoxygenation as previous reported, and cells were then treated with MCU siRNA. Biochemical kits, inductively coupled plasma mass spectrometry (ICP-MS), RT-qPCR, and transmission electron microscopy were used to assess the effects of Zn2+ on cell viability, cytotoxicity, Zn2+ and ATP content, NAD⁺/NADH ratio, mtDNA copy number, and mitochondrial morphological changes following myocardial I/R. Confocal microscopy and fluorescence microscopy were used to observe the fluorescence changes of Zn2+, mitochondrial membrane potential, protein expression, and mitochondrial Ca2+. The effects of Zn2+ on protein expression levels were evaluated using molecular docking and Western blot analysis.
Results
Compared to the Control group, the I/R group exhibited decreased cell viability, and increased cytotoxicity. Intracellular and mitochondrial Zn2+ levels were reduced, accompanied by mitochondrial dysfunction and an increase in mitochondrial Ca2+ content. The expression levels of mitochondrial biosynthesis proteins SIRT1, PGC-1α, NRF1, and TFAM, mitochondrial fusion proteins OPA1, MFN1, and MFN2, as well as MCUb gene and protein expression were downregulated. Conversely, the expression of mitochondrial fission proteins DRP1 and FIS1, along with MCU, MICU1, and MICU2 proteins, was upregulated. Exogenous Zn2+ treatment reversed these alterations. MCU silencing by siRNA further enhanced the protection effects of Zn2+.
Conclusions
I/R induced damage in H9c2 cells and mitochondrial dysfunction. Zn2+ protected H9c2 cells against I/R injury by regulating mitochondrial biogenesis, mitochondrial dynamics, and Ca2+ homeostasis via the MCU, with this protective effect potentially associated with the entire MCU complex.
{"title":"Zn2 + alleviates ischemia/reperfusion injury in H9c2 cells by modulating mitochondrial biogenesis and dynamics via MCU","authors":"Bingyu Wang , Bohan Xing , Luyao Huang , Xiaoyi Li , Xiyun Bian , Jinkun Xi","doi":"10.1016/j.jtemb.2025.127769","DOIUrl":"10.1016/j.jtemb.2025.127769","url":null,"abstract":"<div><h3>Background</h3><div>Zinc is an essential nutrient implicated in cardiovascular health. This study investigates whether Zn<sup>2+</sup> protects H9c2 cells by regulating mitochondrial biogenesis, dynamics, and calcium homeostasis via the mitochondrial calcium uniporter (MCU).</div></div><div><h3>Methods</h3><div>The I/R model were established using simulated ischemia and reoxygenation as previous reported, and cells were then treated with MCU siRNA. Biochemical kits, inductively coupled plasma mass spectrometry (ICP-MS), RT-qPCR, and transmission electron microscopy were used to assess the effects of Zn<sup>2+</sup> on cell viability, cytotoxicity, Zn<sup>2+</sup> and ATP content, NAD⁺/NADH ratio, mtDNA copy number, and mitochondrial morphological changes following myocardial I/R. Confocal microscopy and fluorescence microscopy were used to observe the fluorescence changes of Zn<sup>2+</sup>, mitochondrial membrane potential, protein expression, and mitochondrial Ca<sup>2+</sup>. The effects of Zn<sup>2+</sup> on protein expression levels were evaluated using molecular docking and Western blot analysis.</div></div><div><h3>Results</h3><div>Compared to the Control group, the I/R group exhibited decreased cell viability, and increased cytotoxicity. Intracellular and mitochondrial Zn<sup>2+</sup> levels were reduced, accompanied by mitochondrial dysfunction and an increase in mitochondrial Ca<sup>2+</sup> content. The expression levels of mitochondrial biosynthesis proteins SIRT1, PGC-1α, NRF1, and TFAM, mitochondrial fusion proteins OPA1, MFN1, and MFN2, as well as MCUb gene and protein expression were downregulated. Conversely, the expression of mitochondrial fission proteins DRP1 and FIS1, along with MCU, MICU1, and MICU2 proteins, was upregulated. Exogenous Zn<sup>2+</sup> treatment reversed these alterations. MCU silencing by siRNA further enhanced the protection effects of Zn<sup>2+</sup>.</div></div><div><h3>Conclusions</h3><div>I/R induced damage in H9c2 cells and mitochondrial dysfunction. Zn<sup>2+</sup> protected H9c2 cells against I/R injury by regulating mitochondrial biogenesis, mitochondrial dynamics, and Ca<sup>2+</sup> homeostasis via the MCU, with this protective effect potentially associated with the entire MCU complex.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127769"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-25DOI: 10.1016/j.jtemb.2025.127768
João Marcos Carvalho-Silva, Andréa Cândido dos Reis
Objectives
This systematic review aimed to answer the following question: "Do silver (AgNPs) and selenium (SeNPs) nanoparticles, either individually or incorporated into materials and products, exhibit antiviral activity against SARS-CoV-2 strains?"
Methods
This review was registered in PROSPERO and conducted following the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was performed in PubMed, Scopus, Embase, LILACS, ScienceDirect, Google Scholar, and ProQuest in March 2025 to identify studies evaluating the effects of isolated or material-incorporated AgNPs and SeNPs against SARS-CoV-2.
Results
AgNPs and SeNPs exhibit strong virucidal and antiviral activity against SARS-CoV-2 and its Spike glycoprotein, both as isolated nanoparticles and when incorporated into masks, goggles, polymers, sprays, coatings, mouthwashes, and solutions. High efficacy has been demonstrated across in vitro, in vivo, and clinical studies, with enhanced outcomes associated with smaller particle sizes, higher concentrations, and longer contact times.
Conclusion
Both isolated and material-integrated AgNPs and SeNPs exhibit high antiviral and virucidal effectiveness against multiple SARS-CoV-2 strains in vitro, in vivo, and in clinical studies.
{"title":"Antiviral activity of silver and selenium nanoparticles against SARS-CoV-2: A comprehensive systematic review of in vitro, in vivo, and clinical evidence","authors":"João Marcos Carvalho-Silva, Andréa Cândido dos Reis","doi":"10.1016/j.jtemb.2025.127768","DOIUrl":"10.1016/j.jtemb.2025.127768","url":null,"abstract":"<div><h3>Objectives</h3><div>This systematic review aimed to answer the following question: \"Do silver (AgNPs) and selenium (SeNPs) nanoparticles, either individually or incorporated into materials and products, exhibit antiviral activity against SARS-CoV-2 strains?\"</div></div><div><h3>Methods</h3><div>This review was registered in PROSPERO and conducted following the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was performed in PubMed, Scopus, Embase, LILACS, ScienceDirect, Google Scholar, and ProQuest in March 2025 to identify studies evaluating the effects of isolated or material-incorporated AgNPs and SeNPs against SARS-CoV-2.</div></div><div><h3>Results</h3><div>AgNPs and SeNPs exhibit strong virucidal and antiviral activity against SARS-CoV-2 and its Spike glycoprotein, both as isolated nanoparticles and when incorporated into masks, goggles, polymers, sprays, coatings, mouthwashes, and solutions. High efficacy has been demonstrated across <em>in vitro</em>, <em>in vivo</em>, and clinical studies, with enhanced outcomes associated with smaller particle sizes, higher concentrations, and longer contact times.</div></div><div><h3>Conclusion</h3><div>Both isolated and material-integrated AgNPs and SeNPs exhibit high antiviral and virucidal effectiveness against multiple SARS-CoV-2 strains <em>in vitro</em>, <em>in vivo</em>, and in clinical studies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127768"},"PeriodicalIF":3.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.jtemb.2025.127766
Suresh Kumar Srinivasamurthy , Piyush Mittal , Ahsas Goyal , Suhas Ballal , Laxmidhar Maharana , Kavita Goyal , Mohit Rana , Haider Ali , Brian Gregory George Oliver , Keshav Raj Paudel , Kamal Dua , Gaurav Gupta
Purpose
To review the role of ferroptosis, an iron-dependent form of regulated cell death, in chronic obstructive pulmonary disease (COPD), and to explore the therapeutic opportunities of iron chelators in mitigating ferroptosis-driven lung injury.
Methods
We performed a structured search of PubMed, Scopus, and Web of Science from inception to Dec 31, 2024, using the terms “ferroptosis,” “iron homeostasis,” “iron chelators,” “lipid peroxidation,” and “COPD.” Of the 86 records identified, 45 met the predefined criteria (relevance to pulmonary iron metabolism, ferroptotic mechanisms, and therapeutic interventions) and were included in the narrative synthesis.
Results
Dysregulated iron handling in COPD leads to increased labile iron pools in airway epithelial cells and alveolar macrophages, promoting Fenton chemistry, reactive oxygen species generation, and lipid peroxidation cascades, which trigger ferroptosis. Classical iron chelators, such as deferoxamine, deferiprone, and deferasirox, have shown efficacy in preclinical models by sequestering redox-active iron and preserving mitochondrial integrity. Novel synthetic chelators and nanoparticle-based delivery systems offer lung-specific iron removal with improved safety. The integration of trace-element biomarkers, including serum ferritin, hepcidin, transferrin saturation, and lipid peroxidation products, provides potential tools for patient stratification and therapy monitoring.
Conclusion
Targeting iron dysregulation and ferroptosis through advanced chelation strategies holds promise as a novel therapeutic approach for COPD. Combining mechanistic insights with precision delivery technologies may enhance treatment efficacy and improve clinical outcomes by mitigating iron-driven oxidative lung injuries.
目的探讨铁中毒(一种铁依赖性的细胞死亡形式)在慢性阻塞性肺疾病(COPD)中的作用,并探讨铁螯合剂在减轻铁中毒引起的肺损伤中的治疗机会。方法我们对PubMed、Scopus和Web of Science从成立到2024年12月31日进行了结构化搜索,使用术语“铁中毒”、“铁稳态”、“铁螯合剂”、“脂质过氧化”和“COPD”。在确定的86例记录中,45例符合预先确定的标准(与肺铁代谢相关,铁下沉机制和治疗干预),并被纳入叙述综合。结果慢性阻塞性肺病患者铁处理失调导致气道上皮细胞和肺泡巨噬细胞中不稳定铁池增加,促进Fenton化学、活性氧生成和脂质过氧化级联反应,从而引发铁死亡。经典的铁螯合剂,如去铁胺、去铁素和去铁素,通过隔离氧化还原活性铁和保持线粒体完整性,在临床前模型中显示出疗效。新型合成螯合剂和纳米颗粒为基础的输送系统提供肺特异性铁去除与提高安全性。微量元素生物标志物的整合,包括血清铁蛋白、肝磷脂、转铁蛋白饱和度和脂质过氧化产物,为患者分层和治疗监测提供了潜在的工具。结论通过先进的螯合策略靶向铁调节失调和铁下垂有望成为COPD治疗的新途径。将机制见解与精确递送技术相结合,可以通过减轻铁驱动的氧化性肺损伤来提高治疗效果和改善临床结果。
{"title":"Ferroptosis and iron homeostasis in chronic obstructive pulmonary disease: Therapeutic opportunities of iron chelators","authors":"Suresh Kumar Srinivasamurthy , Piyush Mittal , Ahsas Goyal , Suhas Ballal , Laxmidhar Maharana , Kavita Goyal , Mohit Rana , Haider Ali , Brian Gregory George Oliver , Keshav Raj Paudel , Kamal Dua , Gaurav Gupta","doi":"10.1016/j.jtemb.2025.127766","DOIUrl":"10.1016/j.jtemb.2025.127766","url":null,"abstract":"<div><h3>Purpose</h3><div>To review the role of ferroptosis, an iron-dependent form of regulated cell death, in chronic obstructive pulmonary disease (COPD), and to explore the therapeutic opportunities of iron chelators in mitigating ferroptosis-driven lung injury.</div></div><div><h3>Methods</h3><div>We performed a structured search of PubMed, Scopus, and Web of Science from inception to Dec 31, 2024, using the terms “ferroptosis,” “iron homeostasis,” “iron chelators,” “lipid peroxidation,” and “COPD.” Of the 86 records identified, 45 met the predefined criteria (relevance to pulmonary iron metabolism, ferroptotic mechanisms, and therapeutic interventions) and were included in the narrative synthesis.</div></div><div><h3>Results</h3><div>Dysregulated iron handling in COPD leads to increased labile iron pools in airway epithelial cells and alveolar macrophages, promoting Fenton chemistry, reactive oxygen species generation, and lipid peroxidation cascades, which trigger ferroptosis. Classical iron chelators, such as deferoxamine, deferiprone, and deferasirox, have shown efficacy in preclinical models by sequestering redox-active iron and preserving mitochondrial integrity. Novel synthetic chelators and nanoparticle-based delivery systems offer lung-specific iron removal with improved safety. The integration of trace-element biomarkers, including serum ferritin, hepcidin, transferrin saturation, and lipid peroxidation products, provides potential tools for patient stratification and therapy monitoring.</div></div><div><h3>Conclusion</h3><div>Targeting iron dysregulation and ferroptosis through advanced chelation strategies holds promise as a novel therapeutic approach for COPD. Combining mechanistic insights with precision delivery technologies may enhance treatment efficacy and improve clinical outcomes by mitigating iron-driven oxidative lung injuries.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127766"},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Selenium (Se) is an essential trace element required by the human body, existing in selenium proteins as selenocysteine (Sec) and selenomethionine (SeMet). Through these proteins, Se exerts its biological effects such as free radical metabolism, antioxidant functions, immune response, reproductive functions, apoptosis, and endocrine hormone regulation. Both selenium deficiency and excess are can cause adverse effects on human health. A growing number of evidence highlights the involvement of selenium and its proteins in the development and progression of cardiovascular diseases (CVD). During hypoxia, the body undergoes a series of changes across all organ systems. Among these, the heart, lungs, and brain—due to their high oxygen demand and metabolic activity—demonstrate particularly prominent manifestations of injury. This review summarizes the effects of selenium/selenoproteins on the cardiovascular system, emphasizing new findings on their roles in hypoxic cardiorespiratory injury. This is to provide a scientific basis for preventing and treating high-altitude illnesses from both environmental and nutritional perspectives.
{"title":"Cardiopulmonary injury in hypoxia and selenium: A review","authors":"Lekang Han , Ting Huang , Zhongzhi Zhao , Zhancui Dang","doi":"10.1016/j.jtemb.2025.127767","DOIUrl":"10.1016/j.jtemb.2025.127767","url":null,"abstract":"<div><div>Selenium (Se) is an essential trace element required by the human body, existing in selenium proteins as selenocysteine (Sec) and selenomethionine (SeMet). Through these proteins, Se exerts its biological effects such as free radical metabolism, antioxidant functions, immune response, reproductive functions, apoptosis, and endocrine hormone regulation. Both selenium deficiency and excess are can cause adverse effects on human health. A growing number of evidence highlights the involvement of selenium and its proteins in the development and progression of cardiovascular diseases (CVD). During hypoxia, the body undergoes a series of changes across all organ systems. Among these, the heart, lungs, and brain—due to their high oxygen demand and metabolic activity—demonstrate particularly prominent manifestations of injury. This review summarizes the effects of selenium/selenoproteins on the cardiovascular system, emphasizing new findings on their roles in hypoxic cardiorespiratory injury. This is to provide a scientific basis for preventing and treating high-altitude illnesses from both environmental and nutritional perspectives.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127767"},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.jtemb.2025.127765
Teresa Urbano , Tommaso Filippini , Barbara R. Cardoso , Lauren A. Wise , Giovanna Zamboni , Annalisa Chiari , Giulia Vinceti , Manuela Tondelli , Alessandro Marti , Marcella Malavolti , Marco Vinceti , Bernhard Michalke
Background
The validity of biomarkers to estimate exposure to selenium (Se) species and selenoproteins in the central nervous system (CNS) is not well studied.
Methods
Among 83 Italian participants with mild cognitive impairment, we estimated total Se and single Se species concentrations in paired serum and cerebrospinal fluid (CSF) samples using anion exchange chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry. In each matrix (serum and CSF), we assessed associations between: 1) paired Se species and 2) total Se and Se species.
Results
The distribution of Se exposure was comparable to that generally found in European populations. We found few consistent patterns for most biomarkers, including total Se and some Se species. An exception was a positive association between the two matrices for selenoprotein-P-bound Se and the inorganic Se form selenate, and an unexpected inverse association for glutathione-peroxidase-bound Se. Total Se was positively associated with some Se species but inversely associated with other Se species in serum, while in CSF the positive association was stronger and more consistent across various Se species.
Conclusions
Concentrations of total Se and single Se species in serum were not strongly correlated with their respective concentrations in CSF, the gold standard to estimate CNS exposure. Furthermore, total Se and selected Se species showed consistent positive correlations within CSF but not serum. Our results suggest that relying on serum Se concentrations to assess CNS exposure can introduce error in human studies.
{"title":"Biomarkers of total selenium and selenium species in paired serum and cerebrospinal fluid samples","authors":"Teresa Urbano , Tommaso Filippini , Barbara R. Cardoso , Lauren A. Wise , Giovanna Zamboni , Annalisa Chiari , Giulia Vinceti , Manuela Tondelli , Alessandro Marti , Marcella Malavolti , Marco Vinceti , Bernhard Michalke","doi":"10.1016/j.jtemb.2025.127765","DOIUrl":"10.1016/j.jtemb.2025.127765","url":null,"abstract":"<div><h3>Background</h3><div>The validity of biomarkers to estimate exposure to selenium (Se) species and selenoproteins in the central nervous system (CNS) is not well studied.</div></div><div><h3>Methods</h3><div>Among 83 Italian participants with mild cognitive impairment, we estimated total Se and single Se species concentrations in paired serum and cerebrospinal fluid (CSF) samples using anion exchange chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry. In each matrix (serum and CSF), we assessed associations between: 1) paired Se species and 2) total Se and Se species.</div></div><div><h3>Results</h3><div>The distribution of Se exposure was comparable to that generally found in European populations. We found few consistent patterns for most biomarkers, including total Se and some Se species. An exception was a positive association between the two matrices for selenoprotein-P-bound Se and the inorganic Se form selenate, and an unexpected inverse association for glutathione-peroxidase-bound Se. Total Se was positively associated with some Se species but inversely associated with other Se species in serum, while in CSF the positive association was stronger and more consistent across various Se species.</div></div><div><h3>Conclusions</h3><div>Concentrations of total Se and single Se species in serum were not strongly correlated with their respective concentrations in CSF, the gold standard to estimate CNS exposure. Furthermore, total Se and selected Se species showed consistent positive correlations within CSF but not serum. Our results suggest that relying on serum Se concentrations to assess CNS exposure can introduce error in human studies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127765"},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1016/j.jtemb.2025.127763
Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream
Background
Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.
Objectives
The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.
Methodology
Thirty-two rats were apportioned into control, SA (10 mg kg−1), SA (10 mg kg−1) + AZA (25 mg kg−1), and AZA (25 mg kg−1) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.
Findings
SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.
Conclusion
SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.
{"title":"Cardioprotective potential of azaleatin against sodium arsenite instigated sub-chronic cardiotoxicity via targeting TLR4/MyD88, JAK1/STAT3, and NF-κB in Sprague Dawley rats","authors":"Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream","doi":"10.1016/j.jtemb.2025.127763","DOIUrl":"10.1016/j.jtemb.2025.127763","url":null,"abstract":"<div><h3>Background</h3><div>Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.</div></div><div><h3>Objectives</h3><div>The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.</div></div><div><h3>Methodology</h3><div>Thirty-two rats were apportioned into control, SA (10 mg kg<sup>−1</sup>), SA (10 mg kg<sup>−1</sup>) + AZA (25 mg kg<sup>−1</sup>), and AZA (25 mg kg<sup>−1</sup>) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.</div></div><div><h3>Findings</h3><div>SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.</div></div><div><h3>Conclusion</h3><div>SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127763"},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}