BMC Pharmacology & Toxicology最新文献

{"title":"Protective effects of Alamandine against doxorubicin-induced liver injury in rats.","authors":"Ava Soltani Hekmat, Maryam Hekmat, Sepehr Ramezanipour, Kazem Javanmardi","doi":"10.1186/s40360-025-00932-0","DOIUrl":"https://doi.org/10.1186/s40360-025-00932-0","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX), a common chemotherapeutic agent, is often associated with dose-limiting hepatotoxicity. Alamandine, a peptide of the renin-angiotensin system, has shown antioxidant and anti-inflammatory properties that may counteract these adverse effects.</p><p><strong>Objective: </strong>This study investigated the protective effects of alamandine on DOX-induced liver injury in rats.</p><p><strong>Methods: </strong>Male Wistar rats received DOX (3.75 mg/kg intraperitoneally) on days 14, 21, 28, and 35, reaching a cumulative dose of 15 mg/kg. Alamandine (50 µg/kg/day) was administered continuously via mini-osmotic pumps for 42 days. Liver toxicity was assessed through biochemical measurements of oxidative stress markers, inflammatory cytokines, and liver enzymes, as well as histological examination.</p><p><strong>Results: </strong>DOX administration significantly increased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels while reducing superoxide dismutase (SOD) and catalase (CAT) activity. Histological analysis revealed hydropic degeneration and hepatocyte necrosis. Alamandine co-treatment restored SOD and CAT activity, reduced MDA and inflammatory markers, and normalized liver enzyme levels, indicating significant hepatoprotection. Furthermore, treatment with alamandine reduced the expression of pro-inflammatory cytokines IL-6, IL-1, and NF-κB induced by DOX, while p53 expression remained unchanged.</p><p><strong>Conclusion: </strong>Alamandine effectively mitigates DOX-induced hepatotoxicity, demonstrating its therapeutic potential as an adjunctive agent in chemotherapy through its antioxidant and anti-inflammatory mechanisms.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"95"},"PeriodicalIF":2.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967997","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":"Hepatoprotective activity of bio-fabricated carbon quantum dots-decorated zinc oxide against carbon tetrachloride-induced liver injury in male rats.","authors":"Fatma El-Zahraa S Mohamed, Hebat-Allah S Tohamy, Mohamed El-Sakhawy","doi":"10.1186/s40360-025-00924-0","DOIUrl":"https://doi.org/10.1186/s40360-025-00924-0","url":null,"abstract":"<p><strong>Background: </strong>Cirrhosis is considered as a severe liver disease that causes partial liver damage as well as total liver destruction; It remains a significant health concern. Sugar cane juice is a particularly beneficial beverage, and its waste products are crucial for treating numerous illnesses. As compared to traditional treatments, zinc-doped carbon quantum dots (Zn/CQDs) are easy-to-prepare, economically invested, high nutritive value and environmentally safe substance.</p><p><strong>Materials & methods: </strong>This study investigated the hepatoprotective effects of zinc-doped carbon quantum dots (Zn/CQDs) against carbon tetrachloride (CCl₄)-induced liver injury in male Wistar albino rats. Zn/CQDs were synthesized using a microwave-assisted method and characterized using FTIR and XRD techniques. Meanwhile, a liver Cirrhosis model induced by carbon tetrachloride (CCl₄) was utilized to determine the inhibitory effects of sugar cane juice mixed with Zn/CQDs against liver Cirrhosis. Biochemical parameters, including AST, ALT, and uric acid, were measured to assess liver function. Histopathological analysis was performed to examine liver tissue damage.</p><p><strong>Results: </strong>In this study, Zn/CQDs were extended from 1.62 to 5.45 nm. The results demonstrated that Zn/CQDs exhibited significant hepatoprotective effects by reducing liver enzyme levels and mitigating histopathological changes. However, the study also highlighted the need for further optimization of the used vehicle delivery method, such as sugarcane juice, which is showed a marginal impact on liver function. Sugar cane juice with Zn/CQDs decreased aspartate amino transferase levels (AST) and improved the uric acid concentration. It means a protection from the toxins effect by controlling the liver enzyme levels; but also, elevated levels of alanine aminotransferase (ALT) indicate ongoing liver injury. Overall, this study provides future insights into the potential of sugar cane juice with Zn/CQDs as a high nutritive value additive to drinks and food; it is investigated for plants waste as a novel green therapeutic strategy for liver diseases. Further research is necessary to explore the underlying mechanisms of action and to optimize their formulation for clinical applications.</p><p><strong>Conclusion: </strong>Overall, this study provides promising insights into the potential of Zn/CQDs as a novel green therapeutic strategy for liver diseases.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"94"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972403","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":"Drug-drug interaction among elderly patients in Africa: a systematic review and meta-analysis.","authors":"Tekletsadik Tekleslassie Alemayehu, Gebremariam Wulie Geremew, Addisu Afrassa Tegegne, Gebresilassie Tadesse, Demis Getachew, Habtamu Semagn Ayele, Abebaw Setegn Yazie, Setegn Fentahun, Tesfaye Birhanu Abebe, Tefera Minwagaw, Yilkal Abebaw Wassie","doi":"10.1186/s40360-025-00926-y","DOIUrl":"https://doi.org/10.1186/s40360-025-00926-y","url":null,"abstract":"<p><strong>Background: </strong>Elderly patients are at a heightened risk of drug-drug interactions due to their high prevalence of comorbidities, polypharmacy, and age-related physiological changes that alter drug metabolism and excretion. In Africa, these risks are compounded by unique healthcare challenges, including limited access to diagnostic tools, and high burdens of communicable diseases. The aim of this study is to estimate the prevalence of drug-drug interactions and its associated factors among elderly patients in Africa.</p><p><strong>Methods: </strong>Relevant research articles were identified from databases such as HINARI, Science Direct, Embase, PubMed/MEDLINE, Google Scholar, and Research Gate. Data were extracted via a Microsoft Excel spreadsheet and analyzed via STATA version 11.0. Egger regression tests and funnel plot analysis were used to check for publication bias, and the I² statistic was used to evaluate statistical heterogeneity. Sensitivity and subgroup analyses were also conducted to identify potential causes of heterogeneity.</p><p><strong>Results: </strong>Fifteen articles were analyzed, and a total of 5651 potential drug-drug interactions (pDDIs) were identified in 1952 patients, resulting in an average of 2.89 pDDIs per patient. The overall prevalence of pDDIs among elderly patients was 52.53% (95% confidence interval (CI): 35.40, 69.66). However, the prevalence of pDDIs ranged widely from 2.8 to 90.1%. When the severity of the interactions was considered, the prevalence of pDDIs was 20.59%, 69.4%, 34.32% and 1.59% for major, moderate, minor, and contraindicated DDIs, respectively. Polypharmacy, long hospital stays, hypertension and diabetes mellitus were identified as factors associated with pDDIs among elderly patients in Africa.</p><p><strong>Conclusion: </strong>DDIs are prevalent among elderly patients in Africa and are often associated with polypharmacy, prolonged hospitalizations, and the presence of chronic comorbidities, particularly hypertension and diabetes mellitus. Moderate-severity interactions were the most prevalent DDIs. The study suggests addressing this issue requires targeted interventions, including improved pharmacovigilance, enhanced prescribing practices, and integration of DDI risk assessment into routine clinical care. The study also suggests that the database itself could have modified the DDI prevalence rate. As a result, a single DDI identification database needs to be authorized; otherwise, clinical knowledge should be taken in to account when interpreting the information obtained.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"92"},"PeriodicalIF":2.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963130","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":"Optimization and preparation of in-situ mucoadhesive gel of azithromycin hydroxypropyl-β-cyclodextrin inclusion complex against upper respiratory tract infections.","authors":"Jitu Halder, Shuvam Mishra, Ivy Saha, Ajit Mishra, Ritu Mahanty, Vineet Kumar Rai, Deepak Pradhan, Rakesh Kumar Sahoo, Salim Manoharadas, Muralidhar Tata, Biswakanth Kar, Goutam Ghosh, Goutam Rath","doi":"10.1186/s40360-025-00936-w","DOIUrl":"https://doi.org/10.1186/s40360-025-00936-w","url":null,"abstract":"<p><strong>Background: </strong>Azithromycin (ATM) has limitations, such as poor oral bioavailability and gastrointestinal (GI) side effects that restrict its widespread application.</p><p><strong>Objective: </strong>To develop a localized hydroxy propyl β-cyclodextrin (HP-βCD) inclusion complex-based in situ pH-responsive mucoadhesive gel of azithromycin (ATM) and evaluate its performance for the treatment of upper respiratory tract infections (URTIs).</p><p><strong>Methods: </strong>According to the phase solubility diagram, the ATM HP-βCD complex was prepared and analyzed by FT-IR, DSC, and SEM. Then, using a quality-by-design approach, pH-responsive in-situ gel was prepared. It was characterized in terms of their gelling capacity, pH, spreadability, swelling index, rheological properties and antimicrobial potential.</p><p><strong>Results: </strong>ATM HP- βCD complex 20-fold increased solubility of ATM, i.e., 49.84 ± 1.39 µg/mL with improved dissolution profile compared to pure ATM. Optimized formulation characterized by its gelation pH (6.7), time (1.59 min), and viscosity (1607.9 Pa.s). The developed gel showed a good spreadability index (322.6 ± 0.5%), swelling index (98.26 ± 1.54% after 10 h) and mucoadhesive strength (589 g/cm²). Also, it exhibits a sustained drug release profile for 12 h(94 ± 1.37%) and a broader zone of Staphylococcus aureus growth inhibition (31 ± 3.54 mm).</p><p><strong>Conclusion: </strong>The developed mucoadhesive in situ gels demonstrated promising in vivo performance, primarily due to their effective antimicrobial activity. In vivo, local retention studies confirmed that the formulations adhered to the throat mucosa and remained in place for up to 24 h after application. The findings presented here suggested that this localized delivery system could serve as a useful strategy for improving the therapeutic effects of ATM against URTIs.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"93"},"PeriodicalIF":2.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975179","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":"Quercetin-mediated restoration of high-fat diet-induced male reproductive dysfunction through modifying spermatogenesis and unraveling 3β-HSD, 17β-HSD, and StAR pathways.","authors":"Mona H Hafez, Shereen B Gad, Yasser S El-Sayed","doi":"10.1186/s40360-025-00918-y","DOIUrl":"https://doi.org/10.1186/s40360-025-00918-y","url":null,"abstract":"<p><strong>Purpose: </strong>We explored the astounding potential of quercetin (QRT) to counteract the determinantal impacts of a high-fat diet (HFD) on testicular function in rat model. The goal was to understand how QRT, and its mechanisms of action can protect testicular health from HFD.</p><p><strong>Methods: </strong>Rats were divided into four groups receiving a control diet, QRT supplement (100 mg/kg), HFD, or HFD plus QRT for 8 weeks. Afterward, assessments were conducted, and reproductive organs were analyzed for hormone levels, gene expression, and subjected to biochemical, histopathological, and immunohistochemical analyses.</p><p><strong>Results: </strong>The HFD caused substantial declines in testicular weight, accessory sex glands and epididymis. The HFD also negatively impacted sperm characteristics including reduced motility, viability, and count, along with impaired morphology. Additionally, the HFD decreased testosterone levels in the testes and serum, impaired antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, and reduced expression of key steroid metabolism enzymes 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), and steroidogenic acute regulatory protein (StAR) involved in testosterone synthesis. These changes were paired with enhanced testicular lipid peroxidation, nitrite, and the inflammatory marker tumor necrosis factor-alpha (TNF-α), reflecting the damaging еffеcts of the HFD. Examination of testicular tissues verified structural damage and significantly fewer proliferating cell nuclear antigen (PCNA)-positive spermatogenic cells in seminiferous tubules of HFD-fed group, confirming HFD's adverse еffеcts.</p><p><strong>Conclusion: </strong>QRT supplementation was able to curb the harmful impacts of the HFD on testicular spermatogenesis and steroidogenesis through its antioxidant, anti-inflammatory and androgen boosting properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"90"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963302","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":"Post-marketing safety profile of ganirelix in women: a 20-year pharmacovigilance analysis of global adverse drug event databases (2004-2024).","authors":"Yang Yang, Zhiwei Cui, Xiaoshan Feng, Fan Zou, Xiaoling Wu","doi":"10.1186/s40360-025-00920-4","DOIUrl":"https://doi.org/10.1186/s40360-025-00920-4","url":null,"abstract":"<p><strong>Background: </strong>Ganirelix, a third-generation GnRH antagonist, is widely used in assisted reproductive technology (ART) for rapid pituitary suppression to prevent premature luteinizing hormone (LH) surges. Despite its extensive clinical use, real-world evidence on its safety in large populations remains scarce. This study aimed to evaluate the safety profile of ganirelix by comprehensively analyzing adverse drug events (ADEs) using real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Reporting (JADER) database.</p><p><strong>Methods: </strong>We extracted ADE data from FAERS (Q1 2004-Q2 2024) and JADER (Q1 2009-Q1 2024). Disproportionality analyses, including reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian Confidence Propagation Neural Networks (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS), were employed to identify significant associations between ganirelix and ADEs.</p><p><strong>Results: </strong>In the FAERS database, we identified 1,096 ganirelix-related ADE reports, spanning 26 system organ classes (SOCs). A total of 65 positive signals were detected, including ADEs consistent with drug label such as ovarian hyperstimulation syndrome (OHSS) (n = 290, ROR 2462.76, PRR 2168.48, EBGM05 1655.59, IC025 9.18), injection site pain (n = 54, ROR 3.99, PRR 3.93, EBGM05 3.13, IC025 0.31), and fetal death (n = 6, ROR 21.05, PRR 21.00, EBGM05 10.72, IC025 2.72). Additionally, unexpected signals not listed in the drug label were identified, including ectopic pregnancy (n = 7, ROR 33.02, PRR 32.93, EBGM05 17.64, IC025 3.37), maternal exposure before pregnancy (n = 30, ROR 76.09, PRR 75.16, EBGM05 74.72, IC025 6.22), dermatitis allergic (n = 4, ROR 7.98, PRR 7.97, EBGM05 3.50, IC025 1.33), and bladder tamponade (n = 4, ROR 771.47, PRR 770.3, EBGM05 311.57, IC025 7.80). The median time to ADE onset was 13 days. External validation using the JADER database (62 ganirelix-related ADE reports) confirmed four signals, including abortion (n = 19), OHSS (n = 17), missed abortion (n = 9), and fetal death (n = 8), aligning with FAERS findings.</p><p><strong>Conclusion: </strong>This study provides a robust real-world safety evaluation of ganirelix, with findings corroborated by two independent pharmacovigilance databases. While consistent with clinical observations, the identification of unexpected signals warrants further pharmacoepidemiological investigations to confirm these results.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"91"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978248","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":"Integrative analysis reveals key molecular mechanisms and prognostic model for Ethylnitrosourea-induced gliomagenesis.","authors":"Bo Tan, Tao Chen, Peng Song, Feng Lin, Shuangyin He, Shiyuan Zhang, Xiaohong Yin","doi":"10.1186/s40360-025-00919-x","DOIUrl":"https://doi.org/10.1186/s40360-025-00919-x","url":null,"abstract":"<p><strong>Background: </strong>Ethylnitrosourea (ENU) is a potent mutagen that induces gliomas in experimental models. Understanding the molecular mechanisms underlying ENU-induced gliomagenesis can provide insights into glioma pathogenesis and potential therapeutic targets.</p><p><strong>Methods: </strong>We analyzed gene expression data from GSE16011 and GSE4290 datasets to identify differentially expressed genes (DEGs) associated with gliomagenesis. Comparative Toxicogenomics Database (CTD) was used to identify potential ENU targets. Protein-protein interaction (PPI) network, enrichment analysis, and Cox regression analysis were employed to elucidate key genes and pathways. A risk model was constructed using the TCGA dataset by LASSO analysis, and nomogram and immuno-infiltration analyses were performed.</p><p><strong>Results: </strong>We identified 71 common genes potentially in ENU-induced gliomas. Key hub genes, including TP53, MCL1, CCND1, and PTEN, were highlighted in the PPI network. Enrichment analysis revealed significant GO terms and KEGG pathways, such as \"Neuroactive ligand-receptor interaction\" and \"Glioma.\" A risk model based on 11 prognostic genes was constructed, effectively stratifying patients into low and high-risk groups, with significant differences in overall survival. The model demonstrated high predictive accuracy. The nomogram constructed from ENU-related risk scores showed good calibration and clinical utility. Immuno-infiltration analysis indicated higher immune cell infiltration in high-risk patients. Molecular docking suggested strong binding affinities of ENU with MGMT and CA12.</p><p><strong>Conclusion: </strong>Our integrative analysis identified key genes and pathways implicated in ENU-induced gliomagenesis. The ENU-related risk model and nomogram provide significant prognostic value, offering potential tools for clinical assessment and targeted therapies in glioma patients.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"89"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976158","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":"A real-world pharmacovigilance study of netarsudil based on the FDA adverse event reporting system (FAERS).","authors":"Xiaomei Xiong, Xiuwen Zhang, Fengmin Tang, Taomin Huang","doi":"10.1186/s40360-025-00927-x","DOIUrl":"https://doi.org/10.1186/s40360-025-00927-x","url":null,"abstract":"<p><strong>Background: </strong>The safety information of netarsudil primarily comes from clinical trials experience. This study aimed to explore the ocular and systemic safety of netarsudil through data mining the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>Adverse event (AE) reports submitted to FAERS between January 2018 and September 2024 were extracted. The reporting odd ratio was used to identify netarsudil-related AE signals. Subgroup analysis, time to onset (TTO) analysis and sensitivity analysis were conducted to comprehensively assess the safety profile of netarsudil.</p><p><strong>Results: </strong>A total of 63 AE signals were identified. Thirty-eight were ocular AEs listed in netarsudil's label, with conjunctival hyperemia, vision blurred and eye irritation ranking the top three in reporting frequency. Twenty-one were new ocular AE signals, including allergic blepharitis, eye pruritus, dacryostenosis, myopic shift, corneal hemorrhage, etc. The rest four were unexpected systemic AE signals, including hypersensitivity, swelling face, dermatitis allergic and dermatitis contact. Subgroup analysis showed that patients ≥ 65 years were more likely to develop inflammation-related AEs, whereas the other adult patients were more prone to experience cataract subcapsular, dry eye, refraction disorder and ocular discomfort. The median TTO of netarsudil-related AEs was 1 day (IQR: 0-13 days), with the majority of AEs (82.65%) occurring within the first month of netarsudil administration. Weibull distribution analysis indicated an early failure type, indicating the incidence of AEs decreased over time.</p><p><strong>Conclusion: </strong>This pharmacovigilance study uncovered new ocular and systemic AE signals associated with netarsudil, and found netarsudil-related AEs were more likely to arise shortly after drug administration, offering valuable insights for clinical monitoring, risk identification and future research.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"88"},"PeriodicalIF":2.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967403","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 microemulsion ion-activated gel: a promising ophthalmic delivery system for enhanced corneal protection and sustained release.","authors":"Shao-Hua Dong, Yue Gao, Yue Li, Di Wu, Ying Chen, Shu-He Chen","doi":"10.1186/s40360-025-00922-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00922-2","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate a novel microemulsion ion-activated gel system for the ophthalmic delivery of coenzyme Q10 (CoQ10).</p><p><strong>Methods: </strong>Various CoQ10 microemulsion ion-activated formulations were prepared and fully assessed for physical and chemical parameters, assay and related substances, in vitro release, rheological properties, in vitro cytotoxicity and ophthalmic retention. A preliminary pharmacokinetic study was also performed in rabbits.</p><p><strong>Results: </strong>The formulations met the specified criteria, showing a droplet size of 24.5 ± 2.0 nm for microemulsions, increasing slightly to 39.6 ± 3.5 nm for the microemulsion gels. They exhibited a 24-hour sustained in vitro release (80.0% ± 3.2%) and increased viscosity upon contact with artificial tears containing Ca²⁺ and K⁺ ions. The no-film dissolution method and in vitro models indicated first-order release kinetics (r = 0.987). The preparations demonstrated good tolerance and non-irritating properties, with a Draize score of 0-0.55 in rabbits, and provided a 2-hour extension in drug retention on the ocular surface compared with microemulsions alone. In ultraviolet B (UVB)-exposed rats, corneal epithelial damage was reduced and antioxidant marker levels (superoxide dismutase, malondialdehyde) were significantly improved.</p><p><strong>Conclusion: </strong>This novel system is a promising preparation for ophthalmic CoQ10 delivery, offering sustained release and protection against UVB-induced corneal damage.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"87"},"PeriodicalIF":2.8,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971008","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":"Identification of key therapeutic targets in nicotine-induced intracranial aneurysm through integrated bioinformatics and machine learning approaches.","authors":"Qiang Ma, Longnian Zhou, Zhongde Li","doi":"10.1186/s40360-025-00921-3","DOIUrl":"https://doi.org/10.1186/s40360-025-00921-3","url":null,"abstract":"<p><strong>Background: </strong>Intracranial aneurysm (IA) is a critical cerebrovascular condition, and nicotine exposure is a known risk factor. This study delves into the toxicological mechanisms of nicotine in IA, aiming to identify key biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>Gene Set Variation Analysis (GSVA), Weighted Gene Co-Expression Network Analysis (WGCNA), and enrichment analyses were conducted on differentially expressed genes (DEGs) from the GSE122897 dataset. Additionally, nicotine-related targets were identified using CTD, SwissTargetPrediction, and Super-PRED databases. Integrative machine learning approaches, such as Random Forest (RF) and Support Vector Machine (SVM), were employed to pinpoint key toxicity targets. Molecular docking and immune cell infiltration analyses were also performed.</p><p><strong>Results: </strong>DEGs in IA showed significant alterations in metabolic, secretory, signaling, and homeostatic pathways. Several immune and metabolic response pathways were notably disrupted. WGCNA identified 1127 DEGs with 37 overlapping toxic targets between IA and nicotine. ssGSEA revealed substantial upregulation in immune response and inflammation-related processes. Integrative analyses highlighted TGFB1, MCL1, and CDKN1A as core toxicity targets, confirmed via molecular docking studies. Immune cell infiltration analysis indicated significant correlations between these core targets and various immune cell populations.</p><p><strong>Conclusion: </strong>This study uncovers significant disruptions in metabolic and immune pathways in IA under nicotine influence, identifying TGFB1, MCL1, and CDKN1A as critical biomarkers. These findings offer a deeper understanding of IA's molecular mechanisms and potential therapeutic targets for nicotine-related toxicity.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"86"},"PeriodicalIF":2.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973037","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}