BMC Pharmacology & Toxicology最新文献

{"title":"Cardiac effects of prolonged recombinant human interleukin-11 treatment in severe thrombocytopenia: a retrospective cohort study.","authors":"Xian-Fa Li, Yue Sun, Wen-Rong Wang, Zi-Yang Bao, Yong-Zhong Zhong, Hong-Yu Chen, Dong-Rong Yu, Cai-Feng Zhu, Jun Ni, Bin Zhu","doi":"10.1186/s40360-026-01188-y","DOIUrl":"10.1186/s40360-026-01188-y","url":null,"abstract":"<p><strong>Background: </strong>Recombinant human interleukin-11 (rhIL-11) is commonly used to treat thrombocytopenia induced by cancer chemotherapy. However, concerns about its potential cardiac side effects, especially with prolonged use, warrant further investigation.</p><p><strong>Aim: </strong>This study aimed to evaluate the cardiac effects of prolonged rhIL-11 use by comparing changes in cardiac biomarkers and arrhythmia rates between rhIL-11 and recombinant human thrombopoietin (rhTPO) in patients with severe thrombocytopenia.</p><p><strong>Method: </strong>We conducted a retrospective cohort study of adult patients treated with rhIL-11 or rhTPO for ≥ 5 days between 2015 and 2021. Data were collected at baseline, during treatment, and after discontinuation, focusing on BNP levels and arrhythmia occurrences. Statistical analyses were performed to compare the outcomes between the two groups.</p><p><strong>Results: </strong>Our study cohort comprised 23 patients treated with rhIL-11 and 7 patients receiving rhTPO. The rhIL-11 group showed a significant increase in serum BNP levels from a baseline median of 418 pg/mL (IQR: 193-1205) to 3084 pg/mL (IQR: 1446-5000) within one week (P < 0.01), while the rhTPO group had no significant changes (P = NS). BNP levels in the rhIL-11 group decreased to 384.0 pg/mL (IQR: 239.0-460.0) one week post-discontinuation (P < 0.05). Cardiac arrhythmias were documented in 34.8% (8/23) of rhIL-11-treated patients, demonstrating a clear treatment duration-dependent pattern: 83.3% (5/6) of patients receiving rhIL-11 for more than two weeks developed arrhythmias, with all 3 patients (100%) treated beyond three weeks experiencing cardiac complications, including two cases of frequent ventricular tachycardia. The rhTPO group showed no significant BNP changes or arrhythmic events. Kaplan-Meier survival analysis revealed a statistically significant divergence in arrhythmia risk profiles between the two treatment groups (P < 0.05). Multivariate COX regression analysis identified age as an independent risk factor for arrhythmia development (HR 1.071, 95% CI: 1.007-1.139; p = 0.029).</p><p><strong>Conclusions: </strong>Prolonged rhIL-11 treatment was associated with significant elevations in BNP levels and a higher incidence of arrhythmias, particularly with longer treatment durations. These findings highlight the need for close cardiac monitoring in patients receiving extended rhIL-11 therapy. Further large-scale, prospective studies are necessary to establish clear cardiac safety guidelines for rhIL-11 use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535181","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":"In vitro toxicity of piperazine derivatives involves mitochondrial dysfunction and microtubule-related changes in neuronal cell models.","authors":"Dina Rönnberg, Stig O P Jacobsson","doi":"10.1186/s40360-026-01183-3","DOIUrl":"10.1186/s40360-026-01183-3","url":null,"abstract":"<p><strong>Background: </strong>Piperazine derivatives such as BZP and TFMPP have been used as \"party pill\" substitutes for MDMA and are associated with neurological and cardiovascular toxicity. While their psychoactive effects are largely attributed to monoaminergic mechanisms, the cellular pathways underlying their toxicity are less well defined. Previous in vitro studies indicate mitochondrial dysfunction and oxidative stress, but potential effects on the neuronal cytoskeleton, specifically microtubules, have not been systematically investigated.</p><p><strong>Methods: </strong>The effects of MeOPP, BZP, pFPP and TFMPP were evaluated in retinoic acid-differentiated P19 mouse embryonal carcinoma-derived neurons using complementary assays of cell viability (calcein-AM), metabolic activity (MTT), membrane integrity (LDH), mitochondrial membrane potential (TMRE) and βIII-tubulin immunofluorescence. Key findings were evaluated in differentiated human SH-SY5Y neuroblastoma cells and in Caco-2 human colorectal adenocarcinoma cells. Tubulin polymerization was assessed in a complementary cell-free assay.</p><p><strong>Results: </strong>All compounds induced concentration-dependent toxicity, with marked differences in potency and efficacy. TFMPP was the most active compound across endpoints, producing early and sustained loss of mitochondrial membrane potential followed by reduced viability, cytoskeletal changes and increased membrane damage. BZP and pFPP showed moderate toxicity at higher concentrations, whereas MeOPP had limited effects. Time-course analysis demonstrated that mitochondrial depolarization preceded membrane damage. Reduced βIII-tubulin immunofluorescence in neuronal cells, together with inhibition of tubulin polymerization in a cell-free system, is consistent with effects on microtubule-related processes. Similar toxicity patterns were observed in SH-SY5Y cells, and cytotoxic effects of BZP and TFMPP were also detected in Caco-2 cells.</p><p><strong>Conclusions: </strong>Piperazine derivatives are associated with cellular toxicity characterized by early mitochondrial dysfunction and subsequent effects on the neuronal cytoskeleton. TFMPP showed the most consistent activity across models. The findings indicate that microtubule-related processes may contribute to toxicity and support further mechanistic studies beyond monoaminergic pathways.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454537","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":"Pycnogenol attenuates thioacetamide-induced neurobehavioral impairment and hepatotoxicity via multi-target molecular modulation.","authors":"Selçuk Senyayla, Ahmet Hacimuftuoglu, Cemil Bayram, Selma Sezen, Dilanur Ates, Mehmet Ali Yoruk, Öznur Altunlu, Ufuk Okkay, Ayşenur Budak Savas, Irmak Ferah Okkay, Mustafa Ozkaraca","doi":"10.1186/s40360-026-01175-3","DOIUrl":"10.1186/s40360-026-01175-3","url":null,"abstract":"<p><strong>Background: </strong>Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with liver dysfunction and remains a major cause of mortality among patients with advanced liver disease. This study aimed to evaluate the protective effects of Pycnogenol in a rat model of thioacetamide-induced hepatic encephalopathy.</p><p><strong>Methods: </strong>Thirty-two rats were assigned to four groups: control, HE (TAA), and two treatment groups receiving Pycnogenol at 5 mg/kg and 10 mg/kg. HE was induced by intraperitoneal administration of TAA at 200 mg/kg for three consecutive days. Pycnogenol was administered orally for 14 days prior to and during TAA exposure. Behavioral tests (locomotor activity, elevated plus maze), histopathological evaluations, biochemical parameters, immunohistochemical staining, and gene expression analyses (qPCR) were performed.</p><p><strong>Results: </strong>Pycnogenol administration resulted in significant improvements in locomotor activity, reductions in oxidative stress markers, and decreased expression of IL-1β, TNF-α, NF-κB, and caspase-3. Histopathological examination revealed alleviation of hepatic and neuronal degeneration. Immunohistochemistry confirmed reduced GFAP and iNOS staining in brain tissues.</p><p><strong>Conclusions: </strong>Pycnogenol demonstrated neuroprotective and hepatoprotective effects in this experimental model, likely through modulation of oxidative stress and inflammatory pathways. Although these findings highlight the potential translational relevance of Pycnogenol as a supportive strategy for hepatic encephalopathy, further studies in chronic models and clinical settings are required to confirm its therapeutic applicability.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418435","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":"Optimizing imatinib sampling strategies through a population approach: a crucial step to model-informed precision dosing validation for point-of-care therapeutic drug monitoring.","authors":"Yuan J Pétermann, Junrui Chen, Lavinia Alberi, Simon Alexandra, François Veuve, Eva Choong, Yann Thoma, Roberto Rigamonti, Bruno Da Rocha Carvalho, Sandro Carrara, François R Girardin, Thierry Buclin, Chantal Csajka, Monia Guidi","doi":"10.1186/s40360-026-01181-5","DOIUrl":"10.1186/s40360-026-01181-5","url":null,"abstract":"<p><strong>Background: </strong>Imatinib therapeutic drug monitoring (TDM) contributes at optimizing exposure, yet its implementation is limited by logistical constraints, including strict sampling time requirements. Model-Informed Precision Dosing (MIPD) offers a promising approach to dosage individualization by leveraging population pharmacokinetic (popPK) models, thereby mitigating the constraints of sample collection time. Integrating MIPD and Point-of-Care (POC) analytical methods in ambulatory settings could further improve TDM feasibility and accessibility. This study serves as a proof of concept for MIPD integration in the workflow of imatinib TDM. To identify optimal sampling time for predicting imatinib steady-state trough concentrations (C_{min, SS}) using a popPK model for an MIPD application.</p><p><strong>Methods: </strong>A popPK model developed from data of 146 patients (244 concentrations) was used to simulate individual concentration-time profiles of 1000 patients under standard dosing (400 mg once or twice daily) from treatment initiation to steady-state (reached after 11 days of treatment). Empirical Bayes estimates were generated from single or paired sampling time points and used to predict C_{min, SS}. Predictive performance was evaluated using mean prediction error, coefficient of determination, root mean square prediction error (RMSPE), and successful prediction rates based on recommended therapeutic ranges.</p><p><strong>Results: </strong>Sampling 5-24 h and 1-12 h post-dose for once and twice daily administrations, respectively, yielded an RMSPE < 41% and a successful prediction rate around 70%.</p><p><strong>Conclusion: </strong>The proposed time windows provide flexible sampling strategies, confirming the benefits of MIPD for the convenience of imatinib TDM, thus improving the clinical feasibility of POC TDM.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403431","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":"Short-term repeated-dose oral toxicity and mutagenicity studies on rice-derived glucosylceramides.","authors":"Hiroshi Shimoda, Norityuki Yamazaki, Terry Maniatis, Aldona Kenthol, Kristin Lopez, John C Fanaras, Eirini Karamariti","doi":"10.1186/s40360-026-01182-4","DOIUrl":"https://doi.org/10.1186/s40360-026-01182-4","url":null,"abstract":"<p><strong>Background: </strong>Food-derived glucosylceramides (GlcCer) have been used for functional foods; however, limited information is currently available on their safety. Therefore, we examined the toxicity of repeated oral dose and mutagenicity of rice-derived GlcCer (RGlcCer).</p><p><strong>Methods: </strong>RGlcCer containing 3% GlcCer was administered to mice in a 28-d repeated-dose oral toxicity study. Ames test and in vitro micronucleus test was performed followed OECD guideline.</p><p><strong>Results: </strong>Spontaneous motor suppression, sedation, and convulsions were observed prior to mortality in all animals treated with 6,000 mg/kg/d body weight RGlcCer (equivalent to 180 mg/kg/d body weight of GlcCer). Mice administered 600 mg/kg/d RGlcCer exhibited the same clinical symptoms as the high dose group, although to a milder extent and only during the first half of the treatment period. While a decrease in body weight was noted in the 600 mg/kg/d group, it recovered with continued administration, and no abnormalities were observed in blood, pathological, and anatomical examinations following the treatment period. At a dose of 60 mg/kg/d, no abnormalities were detected in any parameters. No mutagenicity was observed in either in vitro test.</p><p><strong>Conclusion: </strong>The repeated oral administration of 600 mg/kg/d RGlcCer to mice for 28 d was considered safe and the lowest observed adverse effect level was 600 mg/kg/d RGlcCer under our study conditions. The effects of concentrated RGlcCer (CRGlcCer) consisting of 10% rice GlcCer were examined in a mutagenicity study. The results of the Ames test and in vitro micronucleus test showed that CRGlcCer did not induce mutagenic changes. In conclusion, RGlcCer is safe, is not mutagenic, and did not cause chromosomal damage.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403420","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":"Prioritization of molecular signatures between BDE-209-relevant targets and ulcerative colitis: a network toxicology and bioinformatics analysis.","authors":"Yue Zhang, Hai Zhang, Danli Hu, Hailong Zhang, Da Wang, Ziyang Hong, Si Su, Ling Chen","doi":"10.1186/s40360-026-01170-8","DOIUrl":"10.1186/s40360-026-01170-8","url":null,"abstract":"<p><strong>Background: </strong>Decabromodiphenyl ether (BDE-209) is a widely used flame retardant and persistent environmental contaminant. However, the overlap between predicted BDE-209-related targets and ulcerative colitis (UC)-associated molecular signatures has not been systematically evaluated.</p><p><strong>Methods: </strong>Public UC transcriptomic datasets and predicted BDE-209-related targets were integrated for comparative bioinformatic analysis. Differential expression analysis, enrichment analysis, machine learning algorithms, protein-protein interaction network analysis, immune infiltration analysis, single-cell RNA sequencing analysis, and molecular docking were performed to prioritize candidate genes associated with BDE-209-related targets and UC-associated signatures.</p><p><strong>Results: </strong>A total of 87 overlapping genes were identified between predicted BDE-209-related targets and UC-associated differentially expressed genes. Functional enrichment analysis showed that these genes were mainly enriched in inflammation- and immune-related pathways. Machine learning analysis and protein-protein interaction network analysis prioritized eight candidate hub genes (IL1B, MMP9, ICAM1, PPARG, VCAM1, AREG, FABP3, and ACSL5). Immune infiltration and single-cell transcriptomic analyses showed that these genes were mainly expressed in immune-related cell populations within UC datasets. Molecular docking analysis suggested potential structural compatibility between BDE-209 and the protein structures encoded by the identified hub genes.</p><p><strong>Conclusions: </strong>This study identified shared molecular features between predicted BDE-209-related targets and UC-associated transcriptomic signatures. These findings provide a hypothesis-generating resource for future studies investigating the potential relevance of environmental contaminant-related target networks in UC-associated inflammatory contexts.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395848","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":"Coenzyme Q10 as an adjunctive strategy to reduce paclitaxel-induced toxicities in breast cancer: a randomized controlled trial.","authors":"Gehad Hassoub, Noha A El-Bassiouny, Yasser Abdelkader, Ahmed Ashour Badawy, Amira B Kassem","doi":"10.1186/s40360-026-01163-7","DOIUrl":"10.1186/s40360-026-01163-7","url":null,"abstract":"<p><strong>Background: </strong>Paclitaxel is an effective chemotherapeutic agent for breast cancer, but its use is often limited by cumulative toxicities linked to mitochondrial dysfunction and oxidative stress. This study investigated whether Coenzyme Q10 (CoQ10) could mitigate paclitaxel-induced adverse events and improve treatment tolerability.</p><p><strong>Patients and methods: </strong>In this open label randomized controlled trial, 60 patients with breast cancer were randomized (1:1) receive weekly paclitaxel (80 mg/m²) for 12 weeks either alone (control group, n = 30) or in combination with oral CoQ10. The primary outcome was the cumulative incidence of grade ≥ 2 peripheral neuropathy. Secondary endpoints included time-to-onset of grade ≥ 2 neuropathy; fatigue, headache, insomnia, musculoskeletal, gastrointestinal, and hematological adverse events; and left ventricular ejection fraction. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.</p><p><strong>Results: </strong>CoQ10 supplementation was associated with a lower incidence of clinically relevant neuropathy, with grade ≥ 2 events occurring in 68% of the CoQ10 group versus 96% of controls (p = 0.01) with delayed onset of neuropathy (30.0 vs. 20.0 days; log-rank p = 0.005). Significant reductions in severity were also observed for fatigue and insomnia from week 9, and for mucositis, diarrhea, arthralgia, and myalgia from week 11 (p < 0.05). Hemoglobin levels were higher at week 12 (p = 0.009). CoQ10 was associated with preservation of left ventricular ejection fraction (p = 0.005).</p><p><strong>Conclusion: </strong>CoQ10 supplementation during paclitaxel therapy was associated with reduced treatment-related toxicities, preservation of hematologic parameters, and favorable changes in left ventricular ejection fraction, with favorable tolerability.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT06570811) on August 26, 2024. Available at: https://clinicaltrials.gov/study/NCT06570811 .</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387445","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":"Parabens exposure in systemic lupus erythematosus: insights from network toxicology and molecular docking.","authors":"Hui Li, Qin Guo, Tiantian Zhang, Shufen Zhou, Chengshan Guo","doi":"10.1186/s40360-026-01180-6","DOIUrl":"10.1186/s40360-026-01180-6","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease driven by immune dysregulation. Parabens, commonly used preservatives, are potential environmental factors that may influence immune function and contribute to autoimmune diseases like SLE, although the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>A network toxicology approach was used to investigate potential associations between parabens and SLE-related genes. Paraben target genes were identified from ChEMBL, STITCH, and SwissTargetPrediction, while SLE-related genes were obtained from GeneCards, OMIM, and TTD. Shared paraben-SLE genes were subjected using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Hub genes were identified via network analysis with Cytoscape and further evaluated using three gene expression omnibus datasets. Molecular docking simulations were performed to predict potential interactions between parabens and proteins encoded by the identified hub genes.</p><p><strong>Results: </strong>56 shared paraben-SLE genes were identified and were enriched in immune-related processes, including leukocyte proliferation, T cell activation, and cytokine receptor binding. KEGG analysis highlighted enrichment in immune response pathways, including Toll-like receptor (TLR) signaling. Candidate hub genes, including TLR4, cytotoxic T-lymphocyte associated protein 4 (CTLA4), and CD86, were differentially expressed across three independent SLE gene expression datasets. Molecular docking simulations predicted potential binding interactions between parabens and these hub gene proteins.</p><p><strong>Conclusions: </strong>This study identified candidate genes and pathways potentially associated with both paraben exposure and immune dysregulation in SLE, particularly TLR4, CTLA4, and CD86. These findings are based on computational predictions and require further experimental and clinical studies to determine their biological relevance and potential implications for autoimmune diseases.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387086","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":"Biomonitoring-informed neonicotinoid mixture exposure reveals modest cytotoxicity and cell-type-specific molecular responses in human cell lines.","authors":"Li Ma, Xiuying Lin, Yan Wu, Zengheng Xiong, Long Cheng, Shuhai He, Huan Lin","doi":"10.1186/s40360-026-01179-z","DOIUrl":"10.1186/s40360-026-01179-z","url":null,"abstract":"<p><strong>Background: </strong>Neonicotinoids (NEOs) are widely detected in environmental matrices and in humans, raising concerns about potential health risks. However, most toxicological studies have focused on single compounds and/or concentrations far exceeding biomonitoring-relevant exposure ranges.</p><p><strong>Methods: </strong>We developed a UPLC-MS/MS method to quantify eight NEOs and five metabolites in human urine. Using environmental monitoring and urinary biomonitoring data from Hainan Island, China, we constructed exposure-informed NEO mixture profiles based on surface water, tap water, and urinary concentrations, and evaluated their cytotoxicity in four human cell lines (A2780, HEK293T, HeLa, and HepG2). Toxicity was assessed via cell viability, oxidative stress, DNA fragmentation, and integrated multi-omics analyses, with the urinary-biomonitoring-informed mixture evaluated across four cell lines and the surface/tap-water mixtures assessed as an initial transcriptomic screen in HEK293T cells.</p><p><strong>Results: </strong>Environmentally relevant mixtures (surface/tap water) elicited only limited transcriptomic changes (≤ 0.34% of genes). In contrast, biomonitoring-informed mixtures (≈ 0.1 µM ΣNEOs) induced modest but detectable dose-dependent cytotoxicity, with viability reductions of 3-8%, modest oxidative stress, and limited increases in DNA fragmentation, with effects distinct from individual compounds at matched concentrations. Transcriptomic analysis revealed cell-type-specific responses converging on three core modules: innate immune-like inflammatory signaling, ER stress/unfolded protein response, and metabolic reprogramming. Metabolomic profiling identified two dominant perturbation patterns-arginine/nitrogen-centered rewiring (A2780 and HEK293T) versus membrane lipid remodeling (HeLa and HepG2).</p><p><strong>Conclusions: </strong>Biomonitoring-informed NEO/metabolite mixtures elicited measurable, cell-specific molecular perturbations within biomonitoring-relevant concentration ranges, engaging coordinated stress and adaptation programs. These findings support the incorporation of mixture composition and biomonitoring-relevant concentration ranges into future toxicological evaluation.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374390","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":"Meta-analysis of clinical trials assessing the safety of pharmacological treatments for muscular degeneration in Duchenne muscular dystrophy.","authors":"Gerard Ompad, Petra Maria Saura, Nicole Sonne Heckmann, Andrea Rossi, Elena Olmastroni, Manuela Casula, Maurizio Sessa","doi":"10.1186/s40360-026-01178-0","DOIUrl":"10.1186/s40360-026-01178-0","url":null,"abstract":"<p><strong>Introduction: </strong>Currently, there is a lack of meta-analysis providing precise incidence estimates of adverse drug reactions (ADRs) and associated risk differences (RDs) linked to pharmacological treatments for muscle degeneration in Duchenne Muscular Dystrophy (DMD).</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, and ClinicalTrials.gov (January 1, 2000-June 5, 2026) identified clinical trials evaluating safety of pharmacological treatments for muscle degeneration in DMD. A random-effects meta-analysis estimated ADR incidence, and RDs versus a common reference (givinostat) were derived from the pooled incidences rather than from conventional head-to-head treatment contrasts.</p><p><strong>Results: </strong>Thirteen clinical trials were included. Heterogeneity in ADR incidence across treatments (p < 0.05) was identified. Prednisone and prednisolone showed the highest proportions of serious ADRs. Discrepancies were found compared to Summary of Product Characteristics (SmPC): deflazacort showed higher rates of erythema (+ 1.5%) and pollakiuria (+ 4.8%), while vamorolone showed increased Cushingoid features and appetite (+ 7.0%). Subgroup analyses showed dose- and duration-dependent ADRs for deflazacort and prednisone. A reference-anchored exploratory comparison of pooled incidences showed lower gastrointestinal and hematological ADR risks with corticosteroid monotherapy than with givinostat plus corticosteroids. Deflazacort showed lower risks of diarrhea (RD: - 0.3860), decreased appetite (RD: - 0.3160), and decreased platelet count (RD: - 0.4110).</p><p><strong>Conclusion: </strong>Precise ADR estimates can support decision-making in DMD care, helping clinicians balance safety and efficacy, address family concerns, and promote adherence by contextualizing treatment risks.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359310","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}