Toxicology letters最新文献

{"title":"Enhancement of cigarette smoke extract-induced goblet cell metaplasia and hyperplasia exerted through IL-13 receptor α1 expression","authors":"Akina Mori,&nbsp;Risa Matsumoto,&nbsp;Sakuya Ichikawa,&nbsp;Kanae Ishimori,&nbsp;Shigeaki Ito","doi":"10.1016/j.toxlet.2025.06.010","DOIUrl":"10.1016/j.toxlet.2025.06.010","url":null,"abstract":"<div><div>Chronic airway inflammation, such as that occurring in chronic obstructive pulmonary disease, induces goblet cell metaplasia and hyperplasia (GCMH) and leads to hyperproduction of mucus and thickening of airway walls, restricting airflow. Cigarette smoke causes chronic inflammation and GCMH in the airways through a complex mechanism involving various factors, including immune cells. Previous studies reported direct effects of cigarette smoke on epithelial cells. Replicating the physiological condition of immune cells, we assessed the interaction between cigarette smoke extract (CSE) and interleukin (IL)-13, a GCMH inducer, on air-liquid interface-cultured normal human bronchial epithelial cells (NHBEs) from a single non-smoking subject. While single exposure to IL-13 or CSE induced mucus production, as previously reported, co-exposure to IL-13 and CSE synergistically enhanced this effect. We also investigated IL-13 receptor expression, which revealed that CSE exposure significantly induced the expression of the functional IL-13 receptor subunit, IL-13Rα1. To analyze the signaling pathway involved, we exposed NHBE cultures to benzo(a)pyrene, an aryl hydrocarbon receptor (AhR) ligand and constituent of CSE, which increased IL-13Rα1 expression in a concentration-dependent manner. Furthermore, treatment with the AhR inhibitor resveratrol erased the effects of CSE on mucus production and IL-13Rα1 expression. Here, we present a novel pathway to GCMH by which cigarette smoke induces IL-13Rα1 expression through AhR stimulation, making epithelial cells sensitive to IL-13. This discovery not only contributes to our understanding of chronic airway inflammation, but also supports the use of <em>in vitro</em> models to reproduce chronic inflammation without co-culture of epithelial cells and immune cells.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 177-187"},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326902","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":"Occupational exposure to amorphous silica nanoparticles alters lung function and metabolomic features","authors":"Xuemin Shi ,&nbsp;Chen Liang ,&nbsp;LinLin Wang ,&nbsp;Xuefeng Bai ,&nbsp;Ruiyang Ding ,&nbsp;Zhiwei Sun","doi":"10.1016/j.toxlet.2025.06.013","DOIUrl":"10.1016/j.toxlet.2025.06.013","url":null,"abstract":"<div><div>Amorphous silica nanoparticles (SiNPs) are widely produced and used nanomaterials. Although studies have extensively documented SiNPs-induced pulmonary injuries in animal models, the adverse effects on humans remain unclear due to a lack of epidemiological research. In this population-based study, we investigated the effects of occupational exposure to SiNPs on pulmonary function and serum metabolites and explored correlations between these outcomes. We included 15 workers exposed to SiNPs and 45 healthy adults. Chest X-radiography revealed abnormalities such as disordered lung markings and increased lung markings in exposed workers. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume at 1 s (FEV₁) and forced expiratory flow at 25–75 % (FEF_{25 %–75 %}) were significantly lower in the exposed group compared with controls. We used untargeted high-resolution metabolomics to analyze serum metabolites and identified 15 significantly altered metabolites, primarily categorized as lipids and amino acids. Metabolic pathway analysis suggested that SiNPs exposure may disrupt tryptophan metabolism, phenylalanine metabolism, and sphingolipid metabolism. We used Spearman correlation analysis to evaluate relationships between metabolites and pulmonary function. Six metabolites, particularly the environmental pollutants TEMPO and PFOS, showed significant associations with lung function parameters. Therefore, SiNPs may alter the absorption and metabolism of other environmental pollutants. Overall, occupational exposure to SiNPs may impair lung function and disrupt serum metabolite profiles.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 139-146"},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321912","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":"Modulation of SUMO1-TOP1 DNA damage repair by TOPORS following ovalbumin-induced oxidative stress in macrophages","authors":"Xulong Cai ,&nbsp;Qiaolan Xu ,&nbsp;Tongjin Yin ,&nbsp;Xia Li ,&nbsp;Yan Cheng ,&nbsp;Xiangning Li ,&nbsp;Chuangli Hao","doi":"10.1016/j.toxlet.2025.06.012","DOIUrl":"10.1016/j.toxlet.2025.06.012","url":null,"abstract":"<div><div>Allergens, a common trigger of asthma, can lead to increased levels of reactive oxygen species (ROS) and subsequent DNA damage. However, the repair mechanism of DNA damage caused by oxidative stress in allergen-induced asthma is less known. We explored the mechanism by which topoisomerase 1 binding arginine/serine rich protein (TOPORS) regulates small ubiquitin-related modifier 1 (SUMO1) modification of TOP1 to repair DNA damage induced by ovalbumin (OVA). We tested the expression level of TOP1 in asthmatic and healthy children. OVA-induced mouse asthma model was used for further validation. The level of SUMO1-TOP1 in macrophages was studied by immunoprecipitation. The expression of TOP1 was increased in asthmatic children. The expression of TOP1 and γ Histone 2AX (γH2AX) were increased in the lung tissue of asthmatic mice. In OVA-induced macrophages, the levels of TOP1 and γH2AX were increased, while knockdown expression of TOP1 could reduce the level of γH2AX. The level of SUMO1-TOP1 in OVA-induced macrophages was increased. Interestingly, knockdown expression of TOPORS could reduce the levels of SUMO1-TOP1 in OVA-induced macrophages, while the levels of TOP1 and γH2AX were increased. Our results indicate that TOPORS regulates SUMO1 modification of TOP1 and plays an important role in the repair of DNA damage induced by OVA. DNA repair in asthma exacerbation could be a therapeutic target.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 130-138"},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307679","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":"Sublethal effects of diphenyl ether on zebrafish embryo: Developmental, morphological, cardiac and neurotoxic implications","authors":"Shiv Kumar,&nbsp;Pooja Chadha","doi":"10.1016/j.toxlet.2025.06.011","DOIUrl":"10.1016/j.toxlet.2025.06.011","url":null,"abstract":"<div><div>In 2009, the United Nations Environment Programme classified the polybrominated diphenyl ethers (PBDEs) as an emerging class of persistent organic pollutants. In the environment, less brominated diphenyl ethers can be formed by the degradation of PBDEs. In the present study, zebrafish embryo-larvae were exposed to 1.28 mg/L (¹/₄ LC₅₀) and 2.57 mg/L (¹/₂ LC₅₀) of Diphenyl ether (DE) upto 96 h. Effects of sublethal concentrations of DE on acute developmental toxicity, morphology, body growth, heart rate, sinus venosus- bulbus arteriosus (SV-BA) distance, spontaneous movement and sensorimotor response in zebrafish larvae were studied. DE significantly decreased the survival rate and hatchability rate in a concentration dependent manner compared to control. Different types of morphological abnormalities such as pericardial edema, spinal deformity, bent tail, yolk sac edema, crooked body, distorted tail deformities were reported in zebrafish larvae after 96 h of DE exposure. Heart rate was found to be significantly decreased whereas the SV-BA distance was found to be significantly elevated in DE exposed zebrafish larvae. The neurotoxicity markers i.e., sensorimotor response and spontaneous tail coiling movement, were found to be significantly decreased in DE exposed groups when compared to control group. The present investigation will help to understand the detrimental effects of DE in the early life stage of zebrafish.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 169-176"},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326903","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":"Influence of high-dose sodium benzoate on lipopolysaccharide-induced neurobehavioral impairment, oxido-inflammatory brain damage, and cholinergic dysfunction in rats","authors":"Folake Olubukola Asejeje ,&nbsp;Michael Abayomi Abiola ,&nbsp;Oluwatobi Adewumi Adeyemo ,&nbsp;Olalekan Bukunmi Ogunro","doi":"10.1016/j.toxlet.2025.06.008","DOIUrl":"10.1016/j.toxlet.2025.06.008","url":null,"abstract":"<div><div>Sodium benzoate (SB) is a commonly utilized food preservative in the food business. Nonetheless, apprehensions regarding its impact on the brain have garnered worldwide attention. Consequently, we examined the effect of SB on lipopolysaccharide (LPS)-induced neurotoxicity in rats. Twenty-eight male Wistar rats were randomly assigned to four groups: Group 1 (Control, distilled water), Group 2 (SB, 600 mg/kg), Group 3 (LPS, 250 μg/kg/day), and Group 4 (LPS + SB; LPS, 250 μg/kg + SB, 600 mg/kg). SB was administered orally for 14 days, whereas LPS was injected intraperitoneally for 7 days. Upon completion of the treatment, locomotor, motor, and exploratory behaviors were assessed, followed by biochemical, molecular, and histological analyses of the rat brain. Results indicated that SB exacerbated LPS-induced impairments in exploratory behavior and locomotion in rats. Furthermore, SB intensified LPS-induced oxidative stress and cholinergic impairment, as evidenced by reduced levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-S-transferase (GST) activity, alongside an increase in malondialdehyde (MDA) and acetylcholinesterase (AChE) activity in brain tissue. Similarly, exposure to SB led to a substantial elevation in the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), as well as nitric oxide (NO) and myeloperoxidase (MPO) activity in the rat brain. Additionally, histological examination reveals degenerative neurons in the cerebellum, cortex, and hippocampus CA1 and CA3 areas. The outcomes of this study indicate that the co-administration of SB with LPS exacerbated the neurotoxic damage caused by LPS in the rat brain.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 121-129"},"PeriodicalIF":2.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258915","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":"Investigating zinc’s role in mitigating blood lead levels’ toxicity on gut microbiota diversity: NHANES 2007–2010","authors":"Kathyrn R. Ayres ,&nbsp;Juan P. Liuzzi ,&nbsp;Freeman C. Lewis ,&nbsp;Huda M. Mobarki","doi":"10.1016/j.toxlet.2025.06.001","DOIUrl":"10.1016/j.toxlet.2025.06.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Zinc serves as a cofactor for numerous vital processes across species. Microorganisms that make up the gut microbiome rely on these zinc-dependent mechanisms to perform essential functions, contributing to a diverse and stable microbial environment. Environmental contaminants, such as lead, has been shown to disrupt diversity and stability. The purpose of this study was to determine whether zinc serves as an effect modifier against elevated blood lead levels (BLL) on gut microbiota diversity.</div></div><div><h3>Methods</h3><div>The 2007–2008 and 2009–2010 NHANES datasets were utilized to conduct a cross-sectional complex survey analysis aimed at determining whether zinc intake acts as a protective factor against changes in microbiome diversity associated with BLL, using enterolactone (ENL) as a biomarker. A multiple linear regression was conducted to evaluate whether an interaction between BLL and zinc intake could predict ENL. The model included fiber intake and BMI as covariates.</div></div><div><h3>Results</h3><div>BMI and fiber intake were identified as covariates. Fiber intake was a confounding variable in the relationship between zinc and ENL levels. Lead was found to decrease ENL levels (p = 0.002). The interaction between zinc and BLL was marginally significant (p = 0.089).</div></div><div><h3>Conclusion</h3><div>This study suggests that lead’s impact on gut microbial diversity may depend on zinc status. These findings emphasize the importance of accounting for dietary confounders, such as fiber intake, to improve model accuracy and interpretation. While additional research is needed to confirm zinc’s potential protective role, public health strategies encouraging adequate zinc and fiber intake may in part help support microbial resilience and reduce lead’s effects on the gut microbiota.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 107-112"},"PeriodicalIF":2.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249765","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":"Harmful beauty – Temporal profile of urinary phthalate metabolites in tattooed volunteers from Slovakia","authors":"Branislav Kolena ,&nbsp;Natália Prochácková ,&nbsp;Henrieta Hlisníková ,&nbsp;Miroslava Nagyová ,&nbsp;Ida Petrovičová","doi":"10.1016/j.toxlet.2025.06.005","DOIUrl":"10.1016/j.toxlet.2025.06.005","url":null,"abstract":"<div><div>Tattoos are becoming increasingly popular, but tattoo inks often contain harmful chemicals such as phthalates, which are endocrine disruptors. The study aimed to biomonitoring of phthalate metabolites. Seven tattooed subjects were recruited; 24-hour urine samples were collected over five consecutive days. High molecular weight phthalates (HMWP) and low molecular weight phthalates (LMWP) were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC MS/MS), and metabolite profiles were analyzed before and after the tattoo session. Tattoo characteristics and consumer behaviours (CSB) were evaluated. Peak concentrations were observed in 48.94 % of urine samples for LMWP and 47.27 % for HMWP, particularly on or after the tattoo day. Mono-hydroxy-iso-nonyl phthalate (OH-MiNP) concentrations were significantly higher in subjects with colored tattoos (p = 0.029). A positive correlation was observed between mono-iso-nonyl phthalate (MiNP) and tattoo size (r = 0.875, p = 0.010). OH-MiNP (r = 0.759, p = 0.048, Day 1), mono(2-ethylhexyl) phthalate (MEHP, r = 0.767, p = 0.044, Day 5) and mono(2-ethyl-5-carboxypentyl) phthalate (cx MEPP, r = 0.755, p = 0.05, Day 5) were associated with CSB. Tattooing could be a potential source of phthalate exposure, tattoo size, and ink color could play a role. The small sample size of subjects may have influenced the possibility of false positive results.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 96-106"},"PeriodicalIF":2.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144243205","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":"Inhibition of placental 11β-HSD2 expression through cAMP/PKA signaling pathway induces intrauterine growth retardation","authors":"Caiyun Ge ,&nbsp;Luting Yu ,&nbsp;Man Fang ,&nbsp;Xinrui Cao ,&nbsp;Huijun Chen ,&nbsp;Hui Wang","doi":"10.1016/j.toxlet.2025.06.007","DOIUrl":"10.1016/j.toxlet.2025.06.007","url":null,"abstract":"<div><div>It is known that excessive exposure to maternal glucocorticoids during fetal development can cause fetal intrauterine growth retardation (IUGR) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays an important role in the regulation of fetal glucocorticoid level. Our previous study has found that prenatal caffeine exposure (PCE) can inhibit placental 11β-HSD2 expression. However, the epigenetic mechanism and the role of 11β-HSD2 in PCE-induced IUGR remain undetermined. Pregnant Wistar rats were intragastrically administered caffeine (30 and 120 mg/kg·d) on gestational days 9–20. We found that caffeine decreased the fetal body weights, increased maternal/fetal serum and placental corticosterone levels; moreover, it increased placental early growth response factor 1 (EGR1) expression and decreased 11β-HSD2 expression. Further, in HTR-8/SVneo cells, caffeine inhibited the cAMP/PKA signal pathway, increased EGR1 expression, decreased 11β-HSD2 expression, and changed histone modifications (H3K9ac decrease, H3K9me2 increase) in the <em>HSD11B2</em> promoter region. Adenylyl cyclase agonist and EGR1 knockdown all reversed the inhibition of 11β-HSD2 expression by caffeine. It is suggested that the cAMP/PKA/EGR1 signaling pathway mediates caffeine-induced 11β-HSD2 expression inhibition in placental trophoblasts. Finally, using clinical specimens, we confirmed the inhibition of cAMP/PKA signaling pathway, the increase of EGR1/SP1 expression ratio, and the decrease of 11β-HSD2 expression in IUGR placentas. Among them, 11β-HSD2 expression and neonatal birth weight were positively correlated with placental cAMP/PKA signaling pathway, but negatively correlated with EGR1/SP1 expression ratio. In conclusion, the cAMP/PKA signaling pathway and its regulated EGR1/SP1 expression ratio are common regulatory mechanisms of placental 11β-HSD2 in IUGR fetuses. This study elucidates the epigenetic mechanism of PCE on placental 11β-HSD2 expression. Combined with clinical verification, the common mechanism of placental 11β-HSD2 expression down-regulation and IUGR occurrence was proposed, which provided a new idea for exploring early warning and prevention targets of IUGR.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 83-95"},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144229648","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":"Multigenerational toxicity and transcriptomic changes induced by environmentally relevant concentrations of microcystin-LR and -RR in Caenorhabditis elegans","authors":"Xialian Wang ,&nbsp;Jingyi Zhang ,&nbsp;Zhenxiao Cao ,&nbsp;Linglong Dai ,&nbsp;Qin Zhao ,&nbsp;Hua Du","doi":"10.1016/j.toxlet.2025.06.004","DOIUrl":"10.1016/j.toxlet.2025.06.004","url":null,"abstract":"<div><div>Microcystin (MC) contamination in surface water is currently receiving considerable attention as a public health concern. Seasonal occurrence MCs in aquatic environment suggests their long-term impacts on ecosystem and human health, whereas multi-generational toxic effects of MCs were poorly investigated. The reproductive system is the second most important target organ of MCs after the liver. In this study, we examined reproductive toxic effects of the two most prevalent MCs (MC-LR and -RR) on three successive generations of <em>Caenorhabditis elegans</em> through parental exposure, and conducted transcriptomic analysis on P0 and F1 worms. Our results show that parts-per-billion levels of MC-LR and MC-RR disrupt germ cell development in both parental worms and non-exposed F1/F2 progeny. Significant up-regulation of antimicrobial peptide genes was observed in parental worms, while F1 offspring exhibited decreased expression levels of cytochrome P450 genes. The findings reveal multi-generational effects of environmentally relevant concentrations of MCs on reproductive system, and illustrate possible transcriptional changes associated with long term toxicity of MCs.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 58-66"},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211976","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 effect of phthalates on insulin secretion of pancreatic beta cells based on cellular studies, a systematic review","authors":"Kiandokht Ghanati ,&nbsp;Hadi Pourjafar ,&nbsp;Parisa Shavali-gilani ,&nbsp;Nader Akbari ,&nbsp;Gholamreza Tavoosidana ,&nbsp;Farshid Zandsalimi ,&nbsp;Mansoreh Abdolhosseini ,&nbsp;Mina Aghaei ,&nbsp;Parisa Sadighara","doi":"10.1016/j.toxlet.2025.06.002","DOIUrl":"10.1016/j.toxlet.2025.06.002","url":null,"abstract":"<div><div>Diabetes is increasing worldwide. Phthalates are regularly detected in food and ecosystem environments at detectable levels. The purpose of this study was to review and summarize the effect of phthalates on insulin secretion from pancreatic ß-cell. Also, the toxicity of pancreatic ß-cell caused by phthalates and the mechanism of toxicity were discussed in detail. To evaluate the amount of insulin secretion, the cells are usually exposed to two different concentrations of glucose (high and low). In almost all phthalate concentrations at high glucose concentrations, it leads to a decrease in insulin secretion. Furthermore, the most important mechanism in the physiological changes of pancreatic ß-cell was assigned to oxidative stress. The relationship between insulin secretion and oxidative stress parameters with phthalate concentration was identified in all studies. As phthalate concentrations increase, decreased insulin secretion and increased oxidative stress damage are observed in pancreatic beta cells.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 76-82"},"PeriodicalIF":2.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223237","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}