{"title":"Manganese overexposure: Unveiling its neurotoxic potential and involvement in pathogenesis of Parkinson's disease","authors":"Shivani Chib , Shamsher Singh , Randhir Singh , Muhammed Amanat","doi":"10.1016/j.jtemb.2025.127721","DOIUrl":"10.1016/j.jtemb.2025.127721","url":null,"abstract":"<div><h3>Background</h3><div>The modern era has brought increased availability of luxurious goods and conveniences, but manufacturing processes of metals and chemicals, including manganese (Mn), pose health risks. Overexposure of Mn is toxic, leading to neurodegenerative diseases like Parkinson’s disease (PD) which is characterized by dopaminergic neuronal loss. This study aims to investigates the neurotoxic effects of Mn alone and in combination with rotenone in PD-like pathology.</div></div><div><h3>Material and methods</h3><div>Male Wistar rats were treated with manganese chloride (MnCl₂; 15 mg/kg, <em>i.p</em>.) for 28 days. Motor coordination and grip strength were assessed using the strength glass chamber test and string test, respectively. Oxidative stress markers malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured. Inflammatory marker interleukin-6 (IL-6) and apoptotic marker caspase-3 were quantified using ELISA. Dopamine and glutamate levels were analysed in brain homogenates via reversed-phase high-performance liquid chromatography (RP-HPLC).</div></div><div><h3>Results</h3><div>MnCl₂ exposure significantly impaired motor coordination and grip strength. Oxidative stress markers (MDA and LDH) and IL-6 levels were markedly elevated in MnCl₂-treated rats compared to controls (p < 0.05). Apoptosis was evident with increased caspase-3 levels (p < 0.05). Neurotransmitter analysis revealed reduced dopamine and elevated glutamate concentrations (p < 0.05). Notably, combining MnCl2 with lower dose of rotenone successfully mimicked PD-like pathology.</div></div><div><h3>Conclusion</h3><div>Chronic Mn exposure induces oxidative stress, inflammation, and neurotransmitter dysregulation, mimicking Parkinsonian neurotoxicity. This study highlights MnCl₂ as a safer alternative to high-dose rotenone for inducing PD-like symptoms for preclinical PD research. The findings underscore the health risks associated with Mn overexposure and its critical role in PD pathogenesis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127721"},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886118","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}
{"title":"The emerging potential of gallium compounds in medical research: A promising frontier","authors":"Samad Khaksar , Alireza Aliabadi , Rasoul Motahari , Elham Motieiyan , Domenica Marabello , Sara Abdolmaleki","doi":"10.1016/j.jtemb.2025.127724","DOIUrl":"10.1016/j.jtemb.2025.127724","url":null,"abstract":"<div><div>Gallium-based compounds have become increasingly important in medicine due to their remarkable antimicrobial, anti-cancer, and anti-inflammatory properties. In terms of antimicrobial activity, these compounds inhibit the growth of microorganisms by interfering with their essential iron-dependent processes. Gallium competes with iron for binding sites in microbial cells, leading to iron deficiency and subsequent inhibition of microbial growth and replication. In addition, gallium-based compounds have been shown to inhibit the proliferation of cancer cells and induce programmed cell death in various cancer cell lines. Gallium disrupts the iron metabolism of cancer cells, leading to oxidative stress and DNA damage, which ultimately results in cell death. Gallium-based radiotracers have been used for non-invasive imaging of tumors in patients, enabling accurate diagnosis and staging of cancer. In addition, gallium-based compounds have been shown to inhibit the production of inflammatory cytokines and reduce inflammation in various disease models. In this review, many promising results from studies on the medicinal properties of gallium-based compounds are presented, and the structures and mechanisms of action of these compounds are explained as well as possible. However, the toxicity of these compounds is an important factor in exploring their clinical application, which is addressed in this review in the context of the studies conducted in this area.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127724"},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886120","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}
Setayesh Safaei , Mahnaz Azarnia , Elaheh Amini , Mohammad Nabiuni , Media Abdollahian
{"title":"Selenium nanoparticles attenuates silver nanoparticles toxicity in mice Sertoli cells via modulation of SOD and Kindlin-2","authors":"Setayesh Safaei , Mahnaz Azarnia , Elaheh Amini , Mohammad Nabiuni , Media Abdollahian","doi":"10.1016/j.jtemb.2025.127720","DOIUrl":"10.1016/j.jtemb.2025.127720","url":null,"abstract":"<div><div>The rapid increase in male infertility has raised concerns about the potential risks of nanoparticles to male reproductive health. Previous studies have shown that high concentrations of selenium nanoparticles (SeNPs) possess antioxidant properties and can mitigate oxidative stress. However, the impact of SeNPs on supporting Sertoli cells affected by AgNPs has not been studied. This study aimed to investigate the effects of SeNPs on mouse Sertoli cells exposed to AgNPs. Sertoli cells were surgically extracted from NMRI mouse testicles and characterized by flow cytometry. The cells were treated with AgNPs and SeNPs, and their cytotoxicity was analyzed using the MTT assay. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured, and real-time PCR was used to measure the expression of superoxide dismutase (SOD) and Kindlin-2. AgNPs were lethal at a concentration of 10 µg/ml. However, when AgNPs and SeNPs were used together, an increase in the dose of SeNPs (24–64 µg/ml) resulted in improved survival rates of the Sertoli cells (P*** ≤ 0.001). The combination of AgNPs and SeNPs (10 µg/ml + 64 µg/ml, respectively) reduced ROS and MDA levels and upregulated SOD and Kindlin-2 at the transcriptional level (P*** ≤ 0.001). These results suggest that SeNPs can attenuate AgNPs-induced toxicity in Sertoli cells, likely by enhancing the expression of antioxidant genes, reducing the production of ROS and improving reproductive capacity in supportive Sertoli cells. Therefore SeNPs could be suggested as a potential therapeutic agents for reducing the toxic effects of AgNPs <em>in vivo</em>.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127720"},"PeriodicalIF":3.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879572","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}
Wan Ma , Li Jia , Jing Zhao , Yunqin Li , Jingxia Kong , Huahua Du
{"title":"Iron regulates lipid droplet formation in hepatocytes via heme oxygenase-1 mediated ferroptosis","authors":"Wan Ma , Li Jia , Jing Zhao , Yunqin Li , Jingxia Kong , Huahua Du","doi":"10.1016/j.jtemb.2025.127719","DOIUrl":"10.1016/j.jtemb.2025.127719","url":null,"abstract":"<div><h3>Background</h3><div>Iron overload has been implicated in the disruption of hepatic lipid metabolism, potentially contributing to non-alcoholic fatty liver disease and other hepatic disorders. However, the underlying mechanisms connecting iron overload to lipid metabolism dysregulation remain elusive. This study aimed to investigate the effect of iron overload on lipid droplet formation, and to explore the regulatory mechanism of iron overload on lipid metabolism through the lens of ferroptosis.</div></div><div><h3>Methods</h3><div>Iron overload and ferroptosis models were established by treating AML12 mouse hepatocytes with ferric ammonium citrate (FAC) or erastin, a classical ferroptosis inducer, respectively. Lipid droplet formation, mitochondria morphology, and lipid peroxidation index were detected.</div></div><div><h3>Results</h3><div>Perilipin 2 (PLIN2), a lipid droplet-specific marker, exhibited a 1.2-fold increase (<em>p</em> < 0.01) at 50 μM FAC, but decreased by 23 % (<em>p</em> < 0.05) at higher concentrations (250 μM or 500 μM). Similarly, in erastin-induced ferroptosis hepatocytes, PLIN2 expression progressively declined with increasing erastin concentrations, showing a 29 % reduction (<em>p</em> < 0.05) at 30 μM, accompanied by a reduction in both the size and number of lipid droplets. Notably, both FAC and erastin treatments resulted in an initial increase in lipid droplet levels at low concentrations, followed by a decrease at higher concentrations. Additionally, both iron overload and ferroptosis significantly upregulated heme oxygenase-1 (HO-1) expression, whose overexpression exacerbated ferroptosis and diminished lipid storage.</div></div><div><h3>Conclusion</h3><div>Our findings showed that iron overload perturbs hepatocyte lipid metabolism, with ferroptosis playing a pivotal role in lipid regulation through HO-1-mediated mechanisms.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127719"},"PeriodicalIF":3.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865151","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}
{"title":"Long-term toxic effects of nanoparticles on human microbiota","authors":"Shiva Sanati , Azam Bakhti , Fatemeh Mohammadipanah","doi":"10.1016/j.jtemb.2025.127723","DOIUrl":"10.1016/j.jtemb.2025.127723","url":null,"abstract":"<div><div>Synthetic nanomaterials can penetrate various organs, such as the skin, lungs, and gastrointestinal tract, enter systemic circulation, and ultimately reach tissues and human cells. Nanomaterials used in medicine, food, cosmetics, and agricultural processes can accumulate in our intestines and cause dysbiosis. The direct and indirect detrimental impacts of nanomaterials on humans by altering our cells and microbiota are discussed in this paper. These adverse effects of nanomaterials can be slightly reduced by changing their physicochemical characteristics. Some of the gut microbiota can reduce or mitigate the toxicity of nanomaterials through various strategies providing approaches for pro- or postbiotics with detoxifying function. Moreover, nanomaterials influence the rate of horizontal gene transfer. The use of nanomaterials in food, water, and medicines needs to be legitimized based on the duration, dose, type, and level of toxicity. The negative implications of nanomaterials in human cells and their microbiota are surveyed in this paper.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127723"},"PeriodicalIF":3.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913535","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}
{"title":"Uptaken aluminium accumulates in mitochondria","authors":"Mirna Rita Tenan, Stefano Jacopo Mandriota, André-Pascal Sappino","doi":"10.1016/j.jtemb.2025.127718","DOIUrl":"10.1016/j.jtemb.2025.127718","url":null,"abstract":"<div><div>Aluminium is a toxic element and a suspected human carcinogen. Despite this, being highly versatile, currently not classified as a carcinogenic, mutagenic and reprotoxic (CMR) chemical, and widely used, it is absorbed daily from a variety of products. Absorbed aluminium circulates systemically mainly via Transferrin (TF) and accumulates in human organs. Cellular incorporation of aluminium has been unequivocally demonstrated, but the subcellular localisation of the internalised metal requires clarification. Aluminium was previously shown to predominantly accumulate in granular-reticular organelles mainly concentrated in the perinuclear compartment. In this study we investigated the identity of these organelles. To this purpose, we developed a protocol to combine Lumogallion staining, which detects aluminium, with organelle-specific immunofluorescence. In MCF10A human mammary epithelial cells exposed to AlCl<sub>3</sub> for 3 h, aluminium does not co-localise with Calreticulin, a marker of the Endoplasmic Reticulum (ER) - an organelle that forms a network contiguous with the nuclear membrane - thus suggesting that the ER is not the primary site of aluminium accumulation. Neither does aluminium co-localises with TF receptor 1 (TFR1), thus making the involvement of endosomes in the process of aluminium internalisation unlikely. In contrast, in both human and murine mammary epithelial cells, aluminium specific Lumogallion fluorescence tightly co-localises with the fluorescence emitted by the mitochondrial probe MitoTracker in the perinuclear area. Our results provide strong experimental evidence that upon cellular uptake, aluminium accumulates in the mammalian mitochondrion.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127718"},"PeriodicalIF":3.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886119","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}
Hana Sheykhi , Fereshtesadat Fakhredini , Mohammad Javad Khodayar , Darioush Bijan Nejad , Layasadat Khorsandi
{"title":"Possible mechanisms for protective effect of Naringenin on sodium arsenic-induced-testicular toxicity","authors":"Hana Sheykhi , Fereshtesadat Fakhredini , Mohammad Javad Khodayar , Darioush Bijan Nejad , Layasadat Khorsandi","doi":"10.1016/j.jtemb.2025.127722","DOIUrl":"10.1016/j.jtemb.2025.127722","url":null,"abstract":"<div><h3>Background</h3><div>Sodium arsenite (SA), one of the compounds of arsenic, affects multiorgan systems including male reproduction. This study investigated whether Naringenin (NGN) could mitigate sodium SA-induced testicular toxicity by evaluating apoptosis, autophagy, and oxidative stress.</div></div><div><h3>Methodes</h3><div>Male NMRI mice were given 40 mg/L SA in drinking water with or without intragastrically 50 mg/kg NGN for 35 days. Histology, serum testosterone concentration, Bax/Bcl-2 ratio, caspase-3 activity, and expression of autophagy-related biomarkers have been assessed. Malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in testicular tissue were examined for the evaluation of oxidative stress.</div></div><div><h3>Results</h3><div>SA caused histological damage and significantly increased Caspase-3 activity, the Bax/Bcl-2 ratio, while reducing testosterone concentration. Elevated MDA content and GSH, CAT, SOD levels indicate oxidative stress induced by SA in the mouse testicles (p < 0.05). The increased expression of Beclin-1 and ATG5, the elevated ratio of LC3-II/LC3- I proteins, and the diminished expression of the mTOR gene indicate autophagy induced by SA. NGN decreased the Bax/Bcl-2 ratio, and expression of Beclin-1, ATG5, LC3-II/ LC3-I ratio, while increasing mTOR gene expression. NGN could decrease oxidative stress and improve the histology and testosterone concentration in the SA-treated animals.</div></div><div><h3>Conclusion</h3><div>NGN improves spermatogenesis by suppressing apoptosis, autophagy, and oxidative stress in SA-treated mice.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127722"},"PeriodicalIF":3.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867467","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}
Youxing Li , Wenxue Li , Yaqin Pang , Yufang Cen , Rongqing Xiao , Yinxia Lin , Boya Li , Jingyi Lu , Yincai Lan , Ahmad Razali Bin Ishak , Guangzi Qi , Mohd Shukri Bin Mohd Aris
{"title":"Association between serum metal levels and NLRP3 gene polymorphisms with cognitive function in aluminum workers: A combined epidemiological and genetic study","authors":"Youxing Li , Wenxue Li , Yaqin Pang , Yufang Cen , Rongqing Xiao , Yinxia Lin , Boya Li , Jingyi Lu , Yincai Lan , Ahmad Razali Bin Ishak , Guangzi Qi , Mohd Shukri Bin Mohd Aris","doi":"10.1016/j.jtemb.2025.127712","DOIUrl":"10.1016/j.jtemb.2025.127712","url":null,"abstract":"<div><h3>Background</h3><div>Metals, genes, and cognitive function are closely related. This study evaluated serum metal levels, NLRP3 gene polymorphisms, and their association with cognitive function in aluminum workers.</div></div><div><h3>Methods</h3><div>A cross-sectional survey was conducted with 478 aluminum workers. Serum metal levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale. Generalized Linear Models (GLM), Least absolute shrinkage and selection operator (Lasso) regression, Bayesian Kernel Machine Regression (BKMR), and Weighted Quantile Sum (WQS) were used to analyze the relationship between metal exposure, cognitive function, and the interaction with NLRP3 gene polymorphisms.</div></div><div><h3>Results</h3><div>Zinc (Zn) levels were positively associated with MoCA scores (β= 4.73, 95 % CI: 0.54, 8.92). A metal mixture (Na, Zn, Co, Mo, Ti, Sr, Ba) below the 60th percentile also showed a positive correlation with MoCA scores. The NLRP3 rs3806265C/C and rs4612666C/T and T/T genotypes were negatively associated with MoCA scores (β= −0.91, 95 % CI: −1.64, −0.17; β= −0.61, 95 % CI: −1.19, −0.02; β= −0.86, 95 % CI: −1.62, −0.10). In individuals with the C/T genotype of rs3806265 and rs4612666, Zn was positively associated with MoCA scores (β= 5.99, 95 % CI: 0.60, 11.38; β= 6.46, 95 % CI: 0.80, 12.12).</div></div><div><h3>Conclusion</h3><div>Decreased serum Zn levels may increase cognitive dysfunction risk. Individuals carrying the NLRP3 rs3806265C/C and rs4612666C/T or T/T more susceptible to cognitive decline. Individuals carrying the rs3806265C/T and rs4612666C/T genotypes are more likely to cause cognitive decline in the presence of Zn deficiency.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127712"},"PeriodicalIF":3.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840965","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}
Evana Akhtar , Anjan Kumar Roy , Md. Ahsanul Haq , Md. Jakarea , Anjuman Ara , Aliya Naheed , Md. Anisur Rahman , Ondine S. von Ehrenstein , Maria Kippler , Yukiko Wagatsuma , Rubhana Raqib
{"title":"Chronic arsenic exposure and cardiometabolic biomarkers in adolescents in the MINIMat longitudinal study","authors":"Evana Akhtar , Anjan Kumar Roy , Md. Ahsanul Haq , Md. Jakarea , Anjuman Ara , Aliya Naheed , Md. Anisur Rahman , Ondine S. von Ehrenstein , Maria Kippler , Yukiko Wagatsuma , Rubhana Raqib","doi":"10.1016/j.jtemb.2025.127717","DOIUrl":"10.1016/j.jtemb.2025.127717","url":null,"abstract":"<div><div>It is well-established that environmental factors, including pollutants, can increase cardiometabolic disease (CMD) risk in adults, but evidence regarding the influence already perceivable earlier in life is limited. In a longitudinal birth cohort, we have shown that early life arsenic exposure was associated with altered CMD biomarkers among young children. Herein, we assessed whether the association between arsenic exposure and CMD biomarkers persists at adolescent age. MINIMat adolescents (n = 460) who have been repeatedly followed-up from <em>in utero</em> to 4.5, and 9 years were enrolled at 15 years of age. Total urinary arsenic (U-As), blood pressure (BP), as well as plasma lipids [total cholesterol (TC), triglyceride (TG), low density lipoproteins (LDL), high-density lipoproteins (HDL)], oxidized LDL, glucose, and blood hemoglobin A1c (HbA1c) were measured. Associations were explored using multivariate and logistic regression models. Child U-As at 4.5 years (median: 57 µg/L), but not concurrent U-As (median: 29 µg/L), was positively associated with systolic (β=1.71) and diastolic BP (β=1.94) (p < 0.05) in adolescence. Concurrent U-As was non-linearly associated with CMD biomarkers at adolescence, with turning points at U-As 35 µg/L for BP and TG; and 20 µg/L for TC, LDL, HDL, glucose and HbA1C. Above the cut-off, the odds of exceeding normal ranges of systolic and diastolic BP, TC and TG were 1.70, 2.75, 1.90 and 2.25 times higher, respectively, while the odds of having HDL levels below the reference range was 2.70 times higher, compared to those having U-As below the cut-off. Sustained arsenic exposure from early childhood, at relatively low levels, was associated with dyslipidemia in adolescence.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127717"},"PeriodicalIF":3.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831173","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}
Özge Kandemir , Fatih Mehmet Kandemir , Nurhan Akaras , Sefa Küçükler , Cihan Gür , Mustafa İleritürk , Hasan Şimşek , Murat Gül
{"title":"Zingerone ameliorates sodium arsenite-induced cardiotoxicity in rats by suppressing oxidative stress and inflammation via Nrf2 /GCLMGCLC signaling pathways","authors":"Özge Kandemir , Fatih Mehmet Kandemir , Nurhan Akaras , Sefa Küçükler , Cihan Gür , Mustafa İleritürk , Hasan Şimşek , Murat Gül","doi":"10.1016/j.jtemb.2025.127716","DOIUrl":"10.1016/j.jtemb.2025.127716","url":null,"abstract":"<div><div>Arsenic toxicity is a serious threat to human health, transmitted through many factors in the environment, especially water and contaminated food. Epidemiologic studies have reported that arsenite increases mortality and morbidity by causing cardiac damage, but the mechanism of action on cardiotoxicity remains to be elucidated. Zingerone (ZNG) obtained from ginger root is a monomer with pharmacological effects such as antioxidant, anti-inflammatory, and anticancer. This study was conducted to investigate the protective potential of zingerone against sodium arsenite-induced cardiac damage in rats. Sodium arsenite (SA) (10 mg/kg) was administered to rats for 14 days to induce cardiotoxicity, while zingerone (25 and 50 mg/kg) was administered for treatment. Then, oxidative stress markers, inflammatory factors, and apoptosis-related proteins were evaluated by molecular and biochemical methods. It was also supported by histological and immunohistochemical stainings. According to the results, ZNG treatment significantly reduced SA-induced altered cardiac functions. Compared with the SA group, rats co-treated with SA and ZNG showed a significant decrease in oxidant markers and an increase in antioxidant levels. Additionally, ZNG treatment regulated the expression of NRF2, HO-1, NQO1, GCLM, and GCLC genes related to oxidative stress. Moreover, treatment with ZNG significantly inhibited arsenite-induced apoptosis (p53, Apaf-1, Bax, Bcl-2, Casp-3, Casp-6, Casp-9) while reducing the levels of inflammatory mediators including NF-κB, TNF-α, IL-1β, COX-2 and iNOS in cardiac tissue. Finally, co-administration of ZNG with SA reduced SA-induced cardiac histopathological changes in rats. The results of this study suggest that ZNG may provide an alternative for clinical inflammation control through antioxidant and anti-inflammatory activities.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"91 ","pages":"Article 127716"},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826790","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}