Journal of Trace Elements in Medicine and Biology最新文献

{"title":"Elucidation of molecular mechanisms, pathways, and diseases modulated by arsenicals through toxogenomics and multi-omics analysis","authors":"Seema Zargar ,&nbsp;Nojood Altwaijry ,&nbsp;Humidah Alanazi ,&nbsp;Atekah Hazzaa Alshammari ,&nbsp;Hamad M. Alkahtani ,&nbsp;Tanveer A. Wani","doi":"10.1016/j.jtemb.2024.127561","DOIUrl":"10.1016/j.jtemb.2024.127561","url":null,"abstract":"<div><div>Arsenic compounds exist in inorganic and organic forms with inorganic form confirmed as a potent carcinogen. Toxogenomics and multi-omics analysis were used to explore the molecular mechanisms of carcinogenecity induced by arsenicals. Comparative toxogenomics revealed sodium arsenite and arsenate as the most toxic arsenicals to humans, interacting with various genes and altering gene expression through mRNA binding proteins. Both metalloids were classified as Class II toxins by the ProTox II prediction tool, with a lethal dose (LD50) of 149 mg/kg body weight. The most frequently interacting genes were HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM. Analysis of TCGA pan-cancer data revealed that 46 % of hepatocellular carcinoma patients exhibited alterations in the genes HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM, suggesting their significant role in the development of this disease. The alteration in the gene list decreased the overall patient survival but insignificantly in the Kaplan-Meier curves revealing insignificant role in survival. GSEA suggested significant enrichment of the gene list in pathways involved in the G2M checkpoint, apoptosis, hypoxia, TNFA signaling via NFKB, PI3K AKTMTOR signaling, P53, IFN gamma and inflammatory response pathways revealing the involvement of these pathways. Ten microRNAs (miRNAs) regulated the expressions of the genes involved in the above-mentioned pathways with the significant enrichment in miR-21–3p, miR-206 and mir486a-5p. The relevant pathway and graphical representation of the network of miRNA-target interactions identified by the enrichment analysis along with disease ontologies were predicted. This study will be helpful insight into setting of laboratory experiments.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127561"},"PeriodicalIF":3.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635344","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":"Association between urinary arsenic levels and kidney damage in US adults: NHANES 2007–2018","authors":"Nishat Tasnim Hasan ,&nbsp;Xiaohui Xu ,&nbsp;Daikwon Han ,&nbsp;Garett Sansom ,&nbsp;Taehyun Roh","doi":"10.1016/j.jtemb.2024.127559","DOIUrl":"10.1016/j.jtemb.2024.127559","url":null,"abstract":"<div><h3>Background</h3><div>Chronic arsenic exposure is known to be associated with various diseases by inducing multiple organ dysfunctions. Despite the high prevalence of kidney diseases in the US and globally, population-level research on the link between inorganic arsenic and kidney damage remains limited. In our study, we assessed the association between urinary arsenic levels and kidney damage among US adults using a multi-marker approach.</div></div><div><h3>Methods</h3><div>We analyzed data from the National Health and Nutrition Examination Survey (2007–2018). Multivariable logistic regression models were employed to estimate the odds ratios (ORs) for kidney damage based on total urinary arsenic levels and multiple kidney biomarkers, including albuminuria, low estimated glomerular filtration rate (eGFR), hyperuricemia, and elevated blood urea nitrogen (BUN), while adjusting for demographic, socioeconomic, and other risk factors. Total urinary arsenic levels were calculated by summing the levels of arsenous acid (As3), arsenic acid (As5), and their methylated metabolites, monomethylarsinic acid (MMA), and dimethylarsinic acid (DMA). Dimethylarsinic acid (DMA) was calibrated for arsenobetaine using a residual regression method to minimize the influence of seafood-related exposure.</div></div><div><h3>Results</h3><div>After adjusting for covariates, we observed 1.29-fold higher odds (95 % CI 1.01, 1.64) of kidney damage in the highest quartile of urinary arsenic compared to the lowest quartile. Specifically, the odds of albuminuria and hyperuricemia were 1.49-fold (95 % CI 1.09, 2.03) and 1.38-fold (95 % CI 1.01, 1.88) higher, respectively, in the highest quartile. Additionally, for every one-unit increase in the natural log of arsenic levels, significant associations were observed for overall kidney damage (OR 1.10, 95 % CI 1.01, 1.20), albuminuria (OR 1.15, 95 % CI 1.03, 1.29), and hyperuricemia (OR 1.12, 95 % CI 1.02, 1.24) when considering arsenic levels in drinking water as a continuous variable.</div></div><div><h3>Conclusion</h3><div>Our study concludes that higher urinary arsenic levels are positively associated with kidney damage. Further prospective studies are needed to confirm these findings.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127559"},"PeriodicalIF":3.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635324","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":"Metallomic analysis of urine from individuals with and without Covid-19 infection reveals extensive alterations in metal homeostasis","authors":"Ketolly Natanne da Silva Leal ,&nbsp;Ana Beatriz Santos da Silva ,&nbsp;Elisânia Kelly Barbosa Fonseca ,&nbsp;Olívia Brito de Oliveira Moreira ,&nbsp;Lúcio Marco de Lemos ,&nbsp;Marcone Augusto Leal de Oliveira ,&nbsp;Alan J. Stewart ,&nbsp;Marco Aurélio Zezzi Arruda","doi":"10.1016/j.jtemb.2024.127557","DOIUrl":"10.1016/j.jtemb.2024.127557","url":null,"abstract":"<div><h3>Background</h3><div>Metal ions perform important functions in the body and their concentrations in cells and tissues are tightly controlled. Alterations in metal homeostasis can occur in certain disease states including infection. In this study urinary excretion of several metals including calcium, cadmium, cobalt, copper, iron, magnesium, nickel, selenium, and zinc in Covid-19 patients (n=35) and control (n=60) individuals, spanning ages and sexes.</div></div><div><h3>Methods</h3><div>Urinary samples were analysed using ICP-MS and the differences in metal concentrations between the Covid-19-infected and control groups were assessed using multivariate data analysis and univariate data analysis employing Student's t-test and Pearson's correlation, with significance set at p&lt;0.05.</div></div><div><h3>Results</h3><div>The urinary concentrations of all metals analysed were significantly higher in the Covid-infected group (compared to controls), with the exception of copper, which was markedly reduced. The increase in calcium excretion was lower and magnesium excretion greater in Covid-19-positive individuals aged 41 or over compared to those aged 40 or lower. Whilst the increase in iron excretion was lower, and cobalt excretion greater in Covid-19-positive males compared to females.</div></div><div><h3>Conclusions</h3><div>The study highlights significant alterations in the handling of a range of metals in the body during Covid-19 infection. It also highlights both age and sex-specific differences in metal homeostasis. The results suggest an important role for copper in the body during Covid-19 infection and suggests that urinary concentrations of copper and other metals may serve as markers to predict progression of the disease.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127557"},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577833","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":"Zinc deficiency impairs the development of human regulatory B cells from purified B cells","authors":"Mary-Ann Puppa ,&nbsp;Sabrina B. Bennstein ,&nbsp;Henrike J. Fischer,&nbsp;Lothar Rink","doi":"10.1016/j.jtemb.2024.127556","DOIUrl":"10.1016/j.jtemb.2024.127556","url":null,"abstract":"<div><div>Zinc is a vital trace element, important for many different immune processes and adequate functionality. B cell development is known to be dependent on sufficient zinc supply. Recently a regulatory B cell (Breg) population has been identified, as CD19⁺IL-10⁺ B cells, able to regulate immune responses by secretion of anti-inflammatory cytokines, such as IL-10. Due to their promotion of an anti-inflammatory milieu, Bregs could reduce or might even prevent excessive pro-inflammatory responses. Hence, having and maintaining Bregs could be interesting for patients suffering from allergies, asthma, and autoimmune diseases. Therefore, understanding Breg generation, required signaling, and their developmental requirements are important. Since our group could previously show that zinc is important for regulatory T cells, we aimed to determine the effect of zinc deficiency on Breg development from human peripheral blood CD19⁺ B cells. We observed highest Breg generation with a combined stimulus of CD40L and the toll like receptor (TLR) ligand, CpG-ODN2006. Using this stimulus, we observed that zinc deficient medium significantly decreased Breg generation from purified B cells. This was not seen in Bregs generated from peripheral blood mononuclear cells (PBMCs) without B cell enrichment suggesting a compensatory mechanism. In line with literature, our data also confirms Bregs develop from CD19⁺ B cells, since total CD19⁺ frequencies remained unchanged, while Breg frequencies varied between stimuli and zinc media conditions. Our study shows for the first time that zinc deficiency significantly impairs Breg development, which provides an important new perspective for clinical applications and therapeutic strategies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127556"},"PeriodicalIF":3.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc-modulated bidirectional copper transfer across the blood-brain barrier in a porcine brain capillary endothelial cell culture model system","authors":"Denny Pellowski ,&nbsp;Franziska Ebert ,&nbsp;Julia Bornhorst ,&nbsp;Tanja Schwerdtle","doi":"10.1016/j.jtemb.2024.127547","DOIUrl":"10.1016/j.jtemb.2024.127547","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) serves as a crucial interface, regulating the transfer of trace elements (TEs) such as copper (Cu) and zinc (Zn) between the bloodstream and the brain. Cu and Zn are essential for maintaining neural function and enzymatic processes. Understanding the interplay of Cu and Zn with the BBB is crucial for elucidating their roles in neurological health and disease. This study investigates the bidirectional transfer of Cu across the BBB and examines the impact of Zn supplementation on this process using a porcine brain capillary endothelial cell (PBCEC) model. Transendothelial electrical resistance (TEER) and capacitance measurements confirmed barrier integrity upon TE exposure, while quantification of Cu and Zn concentrations <em>via</em> inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) in the culture medium provided essential baseline data. Transfer studies revealed significant increases in basolateral (brain side) Cu concentrations after apical (blood side) Cu incubation, with additional Zn supplementation reducing Cu transfer from apical to basolateral compartments. Conversely, Zn incubation showed no effect on basolateral-to-apical Cu transfer. Surprisingly, it was found that Cu also transferred significantly to the apical compartments when incubated basolaterally, and with slightly higher permeability coefficients than <em>vice versa</em>, indicating a potential role of PBCECs in regulating Cu transport both from blood to brain and from brain to blood. These findings suggest a bidirectional Cu trafficking across PBCECs, only slightly influenced unidirectionally by Zn supplementation, highlighting the intricate interplay between TEs at the BBB. Importantly, no alterations in barrier integrity were observed, underscoring the physiological relevance of the experimental conditions. Overall, this study sheds light on the complex dynamics of Cu and Zn transfer at the BBB, emphasizing the need for comprehensive investigations into TE interactions for a deeper understanding of brain TE homeostasis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127547"},"PeriodicalIF":3.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515476","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":"Unveiling the interaction and combined effects of multiple metals/metalloids exposure to TNF-α and kidney function in adults using bayesian kernel machine regression and quantile-based G-computation","authors":"Kuei-Hau Luo ,&nbsp;Hung-Pin Tu ,&nbsp;Yong-Chuan Chung ,&nbsp;Min-Hsin Huang ,&nbsp;Chen-Cheng Yang ,&nbsp;Tzu-Hua Chen ,&nbsp;Cheng-Hong Yang ,&nbsp;Hung-Yi Chuang","doi":"10.1016/j.jtemb.2024.127552","DOIUrl":"10.1016/j.jtemb.2024.127552","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to multiple metals may cause adverse effects, particularly in the kidneys. However, studies on the combined and interaction effects of metal mixtures on human health remain limited.</div></div><div><h3>Objective</h3><div>The study aims to evaluate the interaction between metals and assess the combined effects of exposure to metal mixtures on tumor necrosis factor-alpha (TNF-α) levels and kidney function</div></div><div><h3>Methods</h3><div>Particular emphasis has been placed on the impact of various metals, including arsenic (As), cadmium (Cd), lead (Pb), as well as essential trace elements, such as cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn), on human health and their potential collective influence on both TNF-α and kidney function. This cross-sectional study analyzed the data of 421 adults who underwent a health examination. Generalized linear model (GLM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation (qgcomp) were used to evaluate the association and joint effects between the metals and TNF-α, as well as kidney function.</div></div><div><h3>Results</h3><div>Increased concentrations of As (β = 0.11, 95 % CI = 0.05, 0.17) and Pb (β = 0.30, 95 % CI = 0.23, 0.37) in the blood were associated with elevated levels of TNF-α, while elevated Cu (β = −0.42, 95 % CI = −0.77, −0.07) levels were linked to a significant reduction in TNF-α. The overall effect of metals mixture showed a significant association with a decline in eGFR and an increase TNF-α in the BKMR model. Qgcomp analysis of the metals mixture (β = −0.06, 95 % CI = −0.07, −0.05) indicated that As, Pb, and Zn were the primary contributors to the reduction in eGFR, while As and Pb were the major contributors in metals mixture (β = 0.12, 95 % CI = 0.08, 0.15) to the elevation of TNF-α levels.</div></div><div><h3>Conclusion</h3><div>Exposure to multiple metals could have joint association with the TNF-α levels and kidney function. Furthermore, TNF-α could act as a mediator between metal mixtures and eGFR.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127552"},"PeriodicalIF":3.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142529974","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":"Chemical elemental composition and human taphonomy: A comparative analysis between skeletonised and preserved individuals from six Portuguese public cemeteries","authors":"Angela Silva-Bessa ,&nbsp;Rui Azevedo ,&nbsp;Agostinho Almeida ,&nbsp;Lorna Dawson ,&nbsp;Shari L. Forbes ,&nbsp;Maria Teresa Ferreira ,&nbsp;Ricardo Jorge Dinis-Oliveira","doi":"10.1016/j.jtemb.2024.127551","DOIUrl":"10.1016/j.jtemb.2024.127551","url":null,"abstract":"<div><h3>Introduction</h3><div>In Portugal, it is common practice to reuse burial graves in cemeteries with exhumations occurring after a minimum period of three years after entombment. However, if the human remains still retain soft tissues when the grave is opened, inhumations must continue for successive periods of two years until complete skeletonization is achieved. For the past decade, several Portuguese public cemeteries have been struggling with the lack of burial space mainly due to a slow cadaveric decomposition. As such, this work aims to understand if the chemical elemental concentrations found in the depositional environment of deceased individuals is influencing human taphonomy.</div></div><div><h3>Methods</h3><div>A total of 112 soil samples were collected from graves of five Portuguese public cemeteries and the concentration of 28 chemical elements was measured by inductively coupled plasma mass spectrometry (ICP-MS). A total of 56 head hair samples and 19 fingernail samples were also collected from cadaveric remains and analysed for the same purpose.</div></div><div><h3>Results</h3><div>Overall, all matrices showed statistically significant differences (<em>p</em> &lt; 0.05) between skeletonised and preserved individuals. Although it was considered that the preserved bodies would display higher elemental concentrations than the skeletonised ones, this hypothesis was not confirmed.</div></div><div><h3>Conclusions</h3><div>The authors believe that changes in the burial conditions over time may have enable the disintegration of soft tissues even if they were initially preserved due to the presence of chemical elements. Similar studies on a global scale should be considered as they could bring together distinct perspectives and lead to more comprehensive and innovative solutions for cemetery management.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127551"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium affects sodium balance but not intestinal microbiota - studies in Drosophila melanogaster","authors":"Katharina Jans ,&nbsp;Tobias Jöckel ,&nbsp;Jakob von Frieling ,&nbsp;Ignacio R. Ipharraguerre ,&nbsp;Thomas Roeder ,&nbsp;Kai Lüersen ,&nbsp;Gerald Rimbach","doi":"10.1016/j.jtemb.2024.127548","DOIUrl":"10.1016/j.jtemb.2024.127548","url":null,"abstract":"<div><h3>Background</h3><div>The trace element lithium (Li) is known for its therapeutic mood-stabilizing application in humans, but also for its various bioactivities, which have been uncovered in model organisms. According to the literature, Li may interfere with the homeostasis of other minerals in mammals, namely sodium, calcium and magnesium. In addition, Li was found to influence the composition and diversity of the intestinal microbiota in vertebrates, an observation that may be related to the many bioactivities of Li.</div></div><div><h3>Methods</h3><div>Based on these previous findings, we employed the model organism <em>Drosophila melanogaster</em> to decipher whether Li exhibits similar bioactivities in invertebrates. First, we examined the influence of increasing dietary Li supply (0 −100 mM LiCl) on the status of Li and ten other minerals via Inductively coupled plasma - mass spectrometry (ICP-MS) in heads and remaining body parts of the three wildtype strains <em>w</em>^{<em>1118</em>}, Oregon-R-C and Canton-S. In addition, we investigated the potential impact of Li feeding (0, 0.1, 1 mM LiCl) on the total bacterial load, α- and β-diversity via real-time quantitative polymerase chain reaction (RT q-PCR) and 16S rDNA sequencing in the intestines of female <em>w</em>^{<em>1118</em>}.</div></div><div><h3>Results</h3><div>Our observations revealed that Li accumulates linearly in both sexes and all body parts of the three <em>Drosophila</em> strains as the dietary Li supply increases. While the status of most elements remained unchanged, the sodium levels of the fly also correlated positively with the Li content of the diet. The intestinal microbiota, however, remained largely unaffected by Li feeding in terms of both, bacterial load and diversity.</div></div><div><h3>Conclusion</h3><div>These findings support the hypothesis that elevating the Li supply affects sodium homeostasis in <em>Drosophila</em>, a finding coherent with observations in mammals. Furthermore, our data opposes a possible involvement of the bacterial intestinal colonization in the bioactivity of Li in <em>Drosophila</em>.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127548"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephropathy induced by cisplatin results from mitochondrial disruption, impaired energy metabolism, altered expression of renal transporters, and accumulation of urinary toxins","authors":"Mingkang Zhang ,&nbsp;Jianping Zhang ,&nbsp;Yanrong Ma ,&nbsp;Yongwen Jin ,&nbsp;Yile Li ,&nbsp;Xin’an Wu","doi":"10.1016/j.jtemb.2024.127553","DOIUrl":"10.1016/j.jtemb.2024.127553","url":null,"abstract":"<div><h3>Background</h3><div>The administration of platinum-based drugs such as cisplatin and its derivatives, which are frequently used during clinical chemotherapy, is highly restricted due to the incidence of nephrotoxicity. The present study focused on investigating cisplatin-induced nephrotoxicity from the perspective of energy metabolism, renal transporter expression and urinary toxin accumulation.</div></div><div><h3>Methods</h3><div>This study investigated cisplatin's toxic effects, including nephrotoxicity, cardiotoxicity, hepatotoxicity, pulmonary toxicity, and splenotoxicity. We used transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to characterize the accumulation of cisplatin in the kidney and the structure of renal mitochondria. The production of reactive oxygen species (ROS) induced by cisplatin in renal tubular epithelial cells was evaluated by in vitro experiments, and apoptosis of renal tubular epithelial cells and alterations to the renal microvasculature were assessed. Metabolites associated with the glycolytic and tricarboxylic acid pathways were measured, and renal transporters expression, autophagy, and urinary toxins (UTs) accumulation were also assessed.</div></div><div><h3>Results</h3><div>Our results reveal that cisplatin-induced varying degrees of damage to the heart, liver, spleen, lungs, and kidneys, including inflammatory and fibrotic damage. Accumulation of cisplatin in renal mitochondria disrupted mitochondrial structure and mitochondrial function, as evidenced by decreased levels of glucose 6-phosphate and ribose 5-phosphate and elevated levels of isocitric acid. Cisplatin-induced accumulation of ROS in renal tubular epithelial cells led to apoptosis and, ultimately, constriction or loss of renal microvasculature. Furthermore, dysregulation of renal transporter expression, activation of autophagy and increased accumulation of UTs was observed.</div></div><div><h3>Conclusion</h3><div>Accumulation of cisplatin in the kidney led to damage to mitochondrial structure and function, apoptosis of renal tubular epithelial cells, constriction or loss of renal microvasculature, dysfunction of renal transporters, activation of autophagy, and accumulation of UTs.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127553"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484446","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 integrated effect of roflumilast and selenium nanoparticles on nephrotoxicity generated by cisplatin through the regulation of the antioxidant and apoptotic pathways","authors":"Nashwa Barakat ,&nbsp;Ehab Ismail ,&nbsp;Faten Zahran","doi":"10.1016/j.jtemb.2024.127555","DOIUrl":"10.1016/j.jtemb.2024.127555","url":null,"abstract":"<div><h3>Aim</h3><div>The current investigations aimed to investigate the potential synergistic effect of Roflumilast (ROF) and Selenium nanoparticles (SeNPs) administration on Cisplatin (Cis) -induced nephrotoxicity.</div></div><div><h3>Materials and methods</h3><div>Fifty male rats were divided into five groups; Control group: animals were administered 0.9 % saline solution. Cis group: animals were injected with a single dose of 6 mg/kg. ROF group: Rats received a dosage of 1.2 mg/kg orally daily for 11 days. SeNPs group: animals orally received 0.5 mg/kg of ROF daily for 11 days. The ROF + SeNPs group was administered both after receiving a Cis injection for 11 days. Animals were sacrificed at 5 and 11 days, and the urine and blood samples were collected on day 5 and day 11 for chemical analysis, while kidney samples were obtained for molecular, histological, and immunohistochemical studies.</div></div><div><h3>Results</h3><div>The levels of serum creatinine, Blood urea nitrogen (BUN), and total protein were elevated in the Cis group compared to the control group <em>(p &lt; 0.05).</em> While the combination of ROF and SeNPs dramatically decreased these values after 5 and 11 days <em>(p &lt; 0.05).</em> In addition, Cis caused renal oxidative stress by elevating MDA levels and suppressing the activities of SOD, GSH, and CAT. Similarly, these effects were modulated by ROF and SeNPs after 11 days <em>(p &lt; 0.05).</em> Furthermore, the concurrent administration of ROF and SeNPs resulted in a significant increase in the expression of HO-1, Nrf2, and Bcl2, while decreasing the expression of BAX and IL-6 compared to the Cis group after 11 days <em>(P &lt; 0.05).</em></div></div><div><h3>Conclusion</h3><div>The study showed that both ROF and SeNPs had significant therapeutic potential in reducing the pathological alterations caused by Cis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127555"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515474","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}