BMC Pharmacology & Toxicology最新文献

{"title":"Obeticholic acid prevents cyclophosphamide-induced placental injury via SIRT1 and TLR4/NF-κB pathways.","authors":"Walaa Yehia Abdelzaher, Hanaa Mohamed Khalaf, Sara M Ahmed, Mina Ezzat Attya, Abdelaleem Abdelnour Mohamed, Asmaa Mohamed Mahmoud Ali, Shereen S Gaber, Ahmed K A Abdel-Hakeem, Enas Mostafa Mohammed, Marwa Hassan","doi":"10.1186/s40360-025-00986-0","DOIUrl":"10.1186/s40360-025-00986-0","url":null,"abstract":"<p><strong>Background: </strong>The aim of the current study is to identify the possible protective effect of obeticholic acid (OCA) on placental injury caused by cyclophosphamide (CP). OCA was administered in the presence and absence of CP.</p><p><strong>Methods: </strong>Thirty-two pregnant female rats were randomly assigned to four groups: control group, OCA group: received OCA (10 mg/kg /day, orally), CP group: received CP 20 mg/kg intraperitoneally at 12th day, OCA + CP group. Placental weight and placental growth factor (PlGF) were measured. Placental oxidative stress parameters (malondialdahide (MDA) and total antioxidant capacity (TAC)), besides Sirtuin type 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), myeloid differentiation factor 88 (Myd88) and caspase-3 biomarkers, were evaluated. Nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) gene expression were also measured. Placental histopathological examination, toll- like receptor4 (TLR4) and forkhead-box transcription factor1 (FOXO1) immunohistochemical study were performed.</p><p><strong>Results: </strong>CP significantly decreased PlGF, placental weight, TAC, SIRT1 and Nrf2 with increased placental MDA, Myd88, caspase-3, NF-κB and TNF-α. Histopathological findings of placental damage and high TLR4, FOXO1 immunoexpressions were detected. OCA significantly increased PlGF level, placental weight and normalized the distributed oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and decrease TLR4 and FOXO1 immunoexpressions.</p><p><strong>Conclusion: </strong>Accordingly, these findings suggest that OCA protects CP-induced placental injury by modulating TLR4/Myd88/NF-κB; SIRT1-dependant signaling pathways.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"156"},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091011","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":"Potential therapeutic role of sex steroids in treating sarcopenia: a network pharmacology and molecular dynamics study.","authors":"Xiangyu Cui, Xiaodong Li, Xin Qi, Dawang Wang, Boyuan Kang, FengJiu Li, Xilin Xu","doi":"10.1186/s40360-025-00978-0","DOIUrl":"10.1186/s40360-025-00978-0","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia, characterized by progressive muscle loss and functional decline in aging, poses significant health challenges. Sex steroids, such as estradiol and testosterone, have potential therapeutic roles in mitigating muscle degeneration. This study explores the molecular mechanisms and targets of sex steroids in the treatment of sarcopenia using network pharmacology, enrichment analysis, machine learning, molecular docking, and molecular dynamics simulations.</p><p><strong>Methods: </strong>We identified potential anti-sarcopenia targets by analyzing the interaction network between sex steroids and their targets, intersecting these with differentially expressed genes (DEGs) from the GSE1428. Enrichment analysis was conducted to determine the functional relevance of these targets. Gene set variation analysis (GSVA) was employed to explore pathway-level differences between age groups. Machine learning algorithms (RF, SVM, XGBoost) identified crucial biomarker genes. A nomogram for predicting sarcopenia was constructed and validated. Molecular docking and molecular dynamics (MD) simulations evaluated the binding interactions and stability of steroid-target complexes.</p><p><strong>Results: </strong>Intersection analysis revealed 69 potential anti-sarcopenia targets. Enrichment analysis highlighted pathways related to muscle function, such as calcium signaling and synaptic transmission. GSVA indicated significant upregulation of DNA damage response and immune response pathways in the older group. Machine learning algorithms pinpointed CFTR, FYN, and PRKCA as top biomarkers. The nomogram demonstrated high predictive accuracy with an AUC of 0.925. Molecular docking showed significant binding affinities of sex steroids with target proteins, further supported by stable RMSD values in MD simulations.</p><p><strong>Conclusion: </strong>Sex steroids, specifically estradiol and testosterone, demonstrate promising interactions with key targets implicated in sarcopenia in silico. These computational findings offer preliminary mechanistic insights into the potential therapeutic role of sex steroids in modulating muscle-related pathways. Further experimental and clinical validation is warranted to assess their translational applicability for sarcopenia treatment.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"155"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941851","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":"The post-marketing safety of Esketamine among older adults(≥ 65): an real-world pharmacovigilance study.","authors":"Bin Deng, Zhiwen Fu, Linjie Li, Yusen Xu, Zihe Yang, Xuejia Zhai, Yongning Lv","doi":"10.1186/s40360-025-00992-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00992-2","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"154"},"PeriodicalIF":2.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941856","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":"Acute, sub-acute and developmental toxicity studies of molybdenum disulfide nanoflowers in rats, as per OECD guidelines.","authors":"Farina Hanif, Aslam Khan, Fareeha Anwar, Haseeb Ullah, Muhammad Furqan Akhtar, Muhammad Imran Khan","doi":"10.1186/s40360-025-00881-8","DOIUrl":"https://doi.org/10.1186/s40360-025-00881-8","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the potential toxic effects of Molybdenum disulfide nano-flowers (MoS₂ NF), which have been suggested as a chemotherapeutic agent, but lack previous toxicity studies.</p><p><strong>Methods: </strong>Acute, sub-acute and developmental toxicity studies were conducted following OECD guidelines 425, 407 and 414, respectively.</p><p><strong>Results: </strong>In the acute toxicity study, female Wistar rats received logarithmic doses (1.75-550 mg/kg) of MoS₂NF over 14 days. Results indicated a decrease in oxidative stress markers (CAT, SOD and GSH) and increased MDA levels, along with significant decrease in organ weight compared to normal control. Alterations in liver enzymes, CBC profile and lipid profile and histopathological analysis were observed in MoS₂ NF groups. Sub-acute toxicity (28-day at 3 and 10 mg/kg in both male and female rats) resulted in increased levels of ALT and AST, decreased levels of CAT, SOD and GSH and increased MDA and urea levels. Sperm analysis in male group showed increased motility and concentration, with more defective morphology. In developmental toxicity studies, a 10 mg/kg dose for 21 days decreased all oxidative markers except MDA, which increased. Fetal crown-to-rump length increased, while uterine SOD, CAT and GSH levels decreased. Histopathology revealed organ damage in both sub-acute and developmental studies. Maternal weight remained unaffected, whereas fetal weight showed an increased.</p><p><strong>Conclusion: </strong>MoS₂ NF exhibited mild-to-moderate toxicity, however, long-term and studies are recommended to assess the safety and therapeutic potential of MoS₂NF.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"153"},"PeriodicalIF":2.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941738","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":"Efficacy of daily versus alternate day oral iron supplementation for management of anaemia among general population: a systematic review and meta-analysis.","authors":"Anupkumar D Dhanvijay, Vipin Patidar, Jayvardhan Singh, Subodh Kumar, Shiv Kumar Mudgal, Seshadri Reddy Varikasuvu, Rajesh Kumar","doi":"10.1186/s40360-025-00984-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00984-2","url":null,"abstract":"<p><strong>Background: </strong>Iron deficiency anemia (IDA) remains a prevalent global health issue. While oral iron therapy is the first-line treatment, the optimal dosing strategy-daily versus alternate-day-remains debated, especially for general population use. Therefore, this review aimed to compare the efficacy and tolerability of daily versus alternate-day oral iron supplementation for IDA in the general population.</p><p><strong>Methods: </strong>Searches were conducted across major databases through March 2025. Risk of bias was evaluated utilizing the Cochrane RoB 2 tool, and the certainty of evidence was graded using GRADE. The primary outcome was change in hemoglobin concentration; secondary outcomes included serum iron, ferritin, transferrin saturation, TIBC, MCV, and adverse events. R Studio software, version 4.2.3, and RevMan used for all analyses.</p><p><strong>Results: </strong>This SRMA (systematic review and meta-analysis) included 11 RCTs involving 1014 participants. The pooled analysis found a small, statistically non-significant increase in hemoglobin with daily dosing over alternate-day (MD: 0.28, 95% CI: -0.01 to 0.56, p = 0.06, z = 1.91). Secondary outcomes revealed no significant differences among groups for serum iron, ferritin, transferrin saturation, TIBC, and MCV. Adverse effects were similar between groups (RR: 1.07, 95% CI: 0.86 to 1.34), though metallic taste was more frequent with daily dosing. Risk of bias was low to moderate across studies. Certainty of evidence was rated very low for most outcomes due to heterogeneity and imprecision.</p><p><strong>Conclusion: </strong>Both daily and alternate-day oral iron supplementation are comparably effective for treating IDA, with alternate-day dosing showing better tolerability. Due to low certainty in evidence, treatment decisions should be individualized pending further high-quality research.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"152"},"PeriodicalIF":2.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941798","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":"Simvastatin inhibits 20-Hydroxyeicosatetraenoic acid formation: docking and in vitro assay.","authors":"Yazun Jarrar, Mansour Almansour, Mansour Al-Sayed Ahmad, Belal O Al-Najjar, Amin A Al-Doaiss, Sireen Abdul Rahim Shilbayeh, Su-Jun Lee","doi":"10.1186/s40360-025-00976-2","DOIUrl":"10.1186/s40360-025-00976-2","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"151"},"PeriodicalIF":2.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871393","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":"Analysis of potential molecular targets and mechanisms of brominated flame retardants in causing osteoarthritis using network toxicology, machine learning, SHAP analysis, and molecular dynamics simulation.","authors":"Yu Liu, Guohang Shen, Zidong Xia, Ruoyan Wang, Yupei Dai","doi":"10.1186/s40360-025-00990-4","DOIUrl":"10.1186/s40360-025-00990-4","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"150"},"PeriodicalIF":2.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871392","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":"Hyperoside mitigates amphotericin B-induced nephrotoxicity in HK-2 cells via bioenergetic and oxidative stress modulation.","authors":"Ekramy M Elmorsy, Huda A Al Doghaither, Ayat B Al-Ghafari, Badriah Abdullah Hifni, Najlaa M M Jawad, Noor A Hakim, Manal S Fawzy, Nagwa M Aly","doi":"10.1186/s40360-025-00985-1","DOIUrl":"10.1186/s40360-025-00985-1","url":null,"abstract":"<p><p>Amphotericin B (Amp-B/FZ), a first-line antifungal, is limited by dose-dependent nephrotoxicity. This study investigated the protective effects of hyperoside (HP), a dietary flavonoid, against FZ-induced renal toxicity in human proximal tubular (HK-2) cells. Molecular docking revealed strong binding affinities of HP with mitophagy (PINK1/PARKIN) and antioxidant (Nrf2/HO-1) regulators, contrasting with FZ's preferential binding to mitochondrial complex I. FZ (30-60 µM) induced cytotoxicity (MTT/LDH), genotoxicity (comet assay), and bioenergetic disruption: ATP depletion (58%), mitochondrial complex I/III inhibition (42-67%), and PINK1/PARKIN dysregulation. FZ elevated reactive species (3.2-fold) and lipid peroxidation (2.8-fold) while suppressing catalase (64%) and superoxide dismutase (51%) activities. qPCR confirmed FZ-induced downregulation of NDUFS1, CYC1, CAT, and SOD2, alongside impaired Nrf2/HO-1 antioxidant signaling. Co-treatment with HP (20-40 µM) attenuated FZ toxicity, restoring ATP (1.8-fold), mitochondrial complex activities (35-49%), and antioxidant defenses (CAT:2.1-fold, SOD:1.7-fold). HP also normalized Nrf2/HO-1 expression and mitigated oxidative/genotoxic damage. These findings highlight HP's dual role in countering FZ-induced mitochondrial dysfunction and oxidative stress, positioning it as a promising nephroprotective adjuvant. Further in vivo validation could advance HP's clinical application in reducing antifungal-associated renal injury.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"149"},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833915","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":"Safety profile of belatacept in a real-life setting: disproportionality analysis of the WHO pharmacovigilance database.","authors":"Alexandre O Gérard, Diane Merino, Nouha Ben Othman, Alexandre Destere, Delphine Viard, Elliot Ewig, Fanny Rocher, Antoine Sicard, Milou-Daniel Drici","doi":"10.1186/s40360-025-00972-6","DOIUrl":"10.1186/s40360-025-00972-6","url":null,"abstract":"<p><strong>Background: </strong>Belatacept is a co-stimulation blocker used in kidney transplant recipients to prevent allograft rejection. Unlike calcineurin inhibitors, belatacept is non-nephrotoxic and may carry a lower risk of cardiovascular and metabolic complications. However, the European Medicines Agency (EMA) Summary of Product Characteristics (SmPC) includes a broad range of adverse drug reactions (ADRs), mostly identified in small clinical trials with cyclosporine as a control, in patients exposed to other immunosuppressants. As real-world data on belatacept safety accumulate, a reassessment of its safety profile becomes essential.</p><p><strong>Methods: </strong>We analyzed pharmacovigilance data from VigiBase^®, the World Health Organization global safety database, to explore discrepancies between postmarketing ADR reports and the belatacept Summary of Product Characteristics (SmPC). A disproportionality analysis was performed using the Information Component, a Bayesian metric, to identify potential pharmacovigilance signals.</p><p><strong>Results: </strong>We retrieved 2795 reports involving belatacept, including 424 (15.2%) fatal cases. The disproportionality analysis highlighted 51 potential signals that were not explicitly listed in the SmPC, such as Clostridium difficile infection, hepatitis B reactivation, and hemophagocytic lymphohistiocytosis. Conversely, 47 (33.1%) of the 142 ADRs classified as \"common\" or \"very common\" in the SmPC, such as Cushing's syndrome or depression, had fewer than three reports in VigiBase^®.</p><p><strong>Conclusions: </strong>This study highlights discrepancies between the belatacept SmPC and real-world pharmacovigilance data. Several labeled ADRs were not reported frequently in VigiBase^®, suggesting that they may be less commonly observed in real-world settings. Others, particularly infections, warrant further scrutiny. Yet, these findings should be interpreted with caution due to the inherent limitations of pharmacovigilance data, including underreporting, reporting bias, and residual confounding. Pharmacovigilance approaches generate signals, but cannot definitively establish or exclude a causal relationship. Nonetheless, these findings suggest the need for periodic reassessment of belatacept's safety profile to ensure accurate and clinically relevant information for healthcare providers.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"147"},"PeriodicalIF":2.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820503","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":"The inhibitory effect of tyrosine kinase inhibitors on angiogenesis in zebrafish and interrelationship with the activation of the PI3K/AKT pathway.","authors":"Lili Yang, Xiaotian Liu","doi":"10.1186/s40360-025-00987-z","DOIUrl":"10.1186/s40360-025-00987-z","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"148"},"PeriodicalIF":2.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820504","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}