BMC Pharmacology & Toxicology最新文献

{"title":"Drug-induced sinusoidal obstruction syndrome: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System (FEARS).","authors":"Cuicui Sun, Xiaoyan Yang, Lili Wang, Linlin Tang, Jinhua Chen","doi":"10.1186/s40360-025-00965-5","DOIUrl":"10.1186/s40360-025-00965-5","url":null,"abstract":"<p><strong>Background: </strong>Hepatic Sinusoidal Obstruction Syndrome (SOS) represents a rare but serious adverse drug reaction. This study aimed to identify the medications most frequently associated with SOS risk through the analysis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>We queried the FAERS database using OpenVigil 2.1 to search for all reported cases of SOS from 2004Q1 to 2022Q3. The 50 most frequently reported medications were ranked based on reported odds ratio (ROR) and proportional reporting ratio (PRR) values. We also compared these drugs with those reported in the LiverTox^® database to assess consistency in hepatotoxicity reporting.</p><p><strong>Results: </strong>A total of 1,976 SOS reports were indentified within the selected study period. Oxaliplatin was the most frequently reported medication associated with SOS, whereas the drug exhibited the strongest association with SOS death was busulfan. Disproportionality analysis revealed that the top five medications with the greatest association with SOS were tioguanine, inotuzumab ozogamicin, gemtuzumab ozogamicin, busulfan, and dactinomycin. Approximately half of the top 50 drugs (28 based on ROR and 27 based on PRR) were not outlined in LiverTox^®.</p><p><strong>Conclusions: </strong>Our study offers a potential list of drugs commonly associated with SOS and identified several novel drugs associated with SOS that had not been previously described in LiverTox^®.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"135"},"PeriodicalIF":2.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666982","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":"Dimethyl fumarate attenuates liver injury in a mouse model of cecal ligation and puncture by modulating inflammatory, angiogenic and pyroptotic pathways.","authors":"Heider Qassam, Ali M Janabi, Karrar Kareem Gaen, Najah Rayish Hadi","doi":"10.1186/s40360-025-00968-2","DOIUrl":"10.1186/s40360-025-00968-2","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a prevalent ailment that significantly affects hospitalized individuals around the globe. It is characterized by uncontrolled inflammatory responses resulting in organ injury and leading to high morbidity and mortality. The liver, a vital organ, is affected by sepsis, resulting in liver dysfunction. Dimethyl fumarate (DMF), which is approved for the treatment of multiple sclerosis, has anti-inflammatory and neuroprotective properties through the inhibition of multiple inflammatory mediators. Hence, the present study aimed to assess the hepatoprotective potential of DMF against sepsis.</p><p><strong>Methods: </strong>Four groups of mice (6 animals per group) were divided into a sham group, which was subjected to only anaesthesia and a midline abdominal incision; the cecal ligation and puncture (CLP) group was anaesthetized and underwent an abdominal incision followed by the ligation of the cecum under the ileocecal valve and perforation twice with a needle; the vehicle group was given a solvent of DMF 1 h before the CLP, and the CLP group received 50 mg/kg of DMF via intraperitoneal (ip) injection 1 h before CLP. Following the procedure (24 h post-CLP), the mice were given unrestricted access to food and drink throughout the day. Serum was used to measure the levels of angiopoietin 2, AST and ALT. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the levels of TNF-α, IL-6, MIF, ICAM-1, F2-isoprostanes, VEGF, and caspase 11 in liver tissues. To evaluate the degree of liver damage, a biopsy of the liver was performed.</p><p><strong>Results: </strong>The results revealed that mice exposed to CLP had high levels of AST and ALT in comparison with sham mice. Furthermore, levels of TNF-α, IL-6, MIF, ICAM-1, F2-isoprostanes, VEGF, and caspase 11 in liver tissues were also notably elevated as compared with sham mice. The levels of these parameters were significantly decreased in septic mice pre-treated with DMF. Mice with CLP showed a severe degree of liver damage as compared with sham mice. DMF pre-treatment mitigated liver injury.</p><p><strong>Conclusion: </strong>This study suggests that DMF has hepatoprotective effects on septic mice via the modulation of inflammation, adhesion molecules, angiopoietin 2 and pyroptosis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"134"},"PeriodicalIF":2.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658338","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":"Manganese mitigates atrazine-induced oxidative stress and hepatorenal toxicity: insights from network pharmacology and in vivo experimentation.","authors":"Solomon E Owumi, Tella T Adedayo, Joseph Chimezie, Bayode Oluwawibe, Harieme Agbarogie, Jesutosin O Babalola, Oludare M Ogunyemi, Uche O Arunsi, Moses T Otunla, Chioma E Irozuru, Ahmad Altayyar, Eziuche A Ugbogu","doi":"10.1186/s40360-025-00966-4","DOIUrl":"10.1186/s40360-025-00966-4","url":null,"abstract":"<p><p>Network analysis has provided valuable insights into the mechanisms underlying the hepatoprotective effects of manganese (Mn) in rats subjected to atrazine (ATZ) intoxication. Key hub genes, including STAT3, PPARG, GSK3B, HIF1A, ESR1, START1, MTOR, PPARA, PARP1, and MMP2, were identified as being involved in oxidative stress response, signalling pathways, nuclear receptor activity, ligand-activated transcription factor activity, and the prolactin signalling pathway. This study also employed in vivo toxicology methods to elucidate the multifaceted mechanisms of Mn-mediated hepatoprotection. Male Wistar rats (n = 30, ± 150 g) were randomly assigned into five groups and treated by gavage for 28 consecutive days: Control (corn oil), ATZ alone (10 mg/kg), Mn alone (10 mg/kg), ATZ + Mn (2.5 mg/kg each), and ATZ + Mn (10 mg/kg each). On day 29, body weights were measured, and biochemical assessments were conducted to evaluate antioxidant enzyme profiles, inflammatory biomarkers, oxidative stress markers, and liver function. Treatment with ATZ significantly reduced (p < 0.05) body weight gain compared to the control group. Markers of liver and kidney dysfunction (AST, ALT, ALP, LDH, GGT, creatinine, and urea) were significantly elevated (p < 0.05) in the ATZ-treated rats. Exposure to ATZ also decreased (p < 0.05) in endogenous antioxidant defences, including superoxide dismutase, catalase, glutathione peroxidase, total sulfhydryl, reduced glutathione, and glutathione-S-transferase. Furthermore, administration of ATZ increased (p < 0.05) oxidative stress and inflammatory biomarkers (xanthine oxidase, hydrogen peroxide, nitric oxide, myeloperoxidase, reactive oxygen and nitrogen species, and lipid peroxidation), as well as DNA fragmentation. Remarkably, Mn treatment (2.5 and 10 mg/kg) counteracted these alterations, mitigating oxidative stress, inflammation, and DNA damage induced by ATZ. Network toxicology findings corroborated these in vivo results, highlighting the ameliorative effects of Mn on ATZ-induced hepatorenal toxicity through diverse biochemical pathways. In conclusion, this study demonstrates that Mn exerts significant hepatoprotective effects against ATZ-induced toxicity, as evidenced by network pharmacology and experimental data insights. The findings suggest that Mn mitigates oxidative stress, inflammation, and hepatorenal damage through multiple molecular and biochemical mechanisms.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"133"},"PeriodicalIF":2.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641751","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":"Cardioprotective effects of carvacrol in the isoproterenol-induced myocardial infarction model.","authors":"Seda Koçak, Kübra Tuğçe Kalkan, Ömürcan Sadettin Aydın, Kübra Öztürk","doi":"10.1186/s40360-025-00967-3","DOIUrl":"10.1186/s40360-025-00967-3","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular diseases are significant health problems that cause high mortality rates worldwide. Myocardial infarction (MI), in particular, is one of the leading conditions among these diseases. The aim of this study is to evaluate the potential therapeutic approach of carvacrol in the treatment of cardiovascular diseases by investigating its protective effects against myocardial infarction through oxidative stress and biomarker levels.</p><p><strong>Materials and methods: </strong>In this study, 28 male Wistar albino rats were used, and divided into 4 groups: Control, Carvacrol, Myocardial Infarction (MI), and MI + Carvacrol. Carvacrol was administered at a dose of 50 mg/kg for six weeks. The induction of MI was performed during the last 2 days of carvacrol administration by administering 100 mg/kg isoproterenol subcutaneously. At the end of the experiment, blood pressure, biomarkers such as troponin T, BNP, GDF-15, and IL-6 were measured, and cardiac tissue was histopathologically examined.</p><p><strong>Results: </strong>The results show that in the MI group, troponin T, BNP, IL-6 and GDF-15 levels were increased, while diastolic blood pressure and heart rate were decreased. In the carvacrol-treated group, troponin T, BNP, IL-6 and GDF-15 levels were decreased. Carvacrol did not significantly affect systolic, diastolic, mean arterial pressure, or heart rate in experimental groups. Moreover, carvacrol decreased necrosis, edema, and mononuclear cell infiltration in the heart tissue, which were increased due to MI.</p><p><strong>Conclusion: </strong>In conclusion, carvacrol demonstrated protective effects against myocardial infarction. Carvacrol alleviated histopathological damage by reducing inflammatory biomarkers. In addition to carvacrol improved troponin T and BNP markers.These findings suggest that carvacrol may be a promising agent in the treatment of cardiovascular diseases. However, more comprehensive and long-term studies are needed to confirm this effect and transfer it to clinical applications.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"132"},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636098","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 and safety of a B-cell-driven rituximab regimen for the treatment of refractory idiopathic membranous nephropathy.","authors":"Kaiqi Guo, Huaxia Zhu, Xingcheng Xu, Lanlan Huang, Huimin Li, Xiaowei Li","doi":"10.1186/s40360-025-00954-8","DOIUrl":"10.1186/s40360-025-00954-8","url":null,"abstract":"<p><strong>Background: </strong>Rituximab (RTX) is known to be effective in the treatment of idiopathic membranous nephropathy (IMN), but the specific dosing regimens have not been standardized. The aim of this retrospective study was to assess the clinical efficacy and safety of a B-cell-driven RTX regimen for the treatment of refractory IMN.</p><p><strong>Methods: </strong>The data of 24 refractory IMN patients who underwent a B-cell-driven RTX regimen at Fuyang People's Hospital of Anhui Medical University between October 2018 and November 2021 were retrospectively analysed.</p><p><strong>Results: </strong>In total, 24 patients, comprising 17 males, with a mean age of 52.17 ± 8.28 years, were enrolled. After treatment with the B-cell-driven RTX regimen, 4 (16.67%) patients achieved complete remission, 11 (45.83%) patients achieved partial remission, the overall treatment efficacy was 62.50%, and there were 4 (16.67%) cases of relapse. The cumulative remission RTX dose was 2.40 g (IQR, 2.10 to 3.50), and the total cumulative RTX dose was 2.85 g (IQR, 2.40 to 4.20). B-cell depletion was achieved in 23 (95.83%) patients after the first dose of RTX was applied and in 1 patient after the second dose of RTX was applied. There was a significant difference in clinical remission between patients with and without a change in anti-PLA2R antibody status from positive to negative (P < 0.001). Two (8.33%) patients experienced infusion reactions, and 5 (20.83%) patients experienced nonserious infections. Treatment was discontinued in one patient due to severe pneumonia.</p><p><strong>Conclusion: </strong>A B-cell-driven RTX regimen can induce partial or complete remission in patients with refractory IMN and is safe.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"131"},"PeriodicalIF":2.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564252","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":"Development and validation of a risk prediction model for meropenem-related thrombocytopenia in patients with pulmonary infection.","authors":"Xiao Wang, Hongqin Ke, Jianyong Zhu, Lijun Zhao, Yanhong Liu, Yan He, Wenwen Wu, Huibin Yu","doi":"10.1186/s40360-025-00962-8","DOIUrl":"10.1186/s40360-025-00962-8","url":null,"abstract":"<p><strong>Objective: </strong>The prevalence of meropenem-related thrombocytopenia has risen in tandem with the growing utilization of meropenem in clinical settings. Consequently, we aimed to develop a risk prediction model for meropenem-related thrombocytopenia in patients with pulmonary infection and to enhance the safety for the clinical administration of meropenem.</p><p><strong>Methods: </strong>A retrospective case-control study was conducted to collect data. The training group consisted of patients who were treated with meropenem for pulmonary infection at a tertiary A hospital in Shiyan from January 2018 to December 2021. The external validation group was formed from patients at another tertiary A hospital from January 2019 to January 2020. Multivariable logistic regression analysis was employed to investigate the risk factors linked to meropenem-related thrombocytopenia. Subsequently, these factors were utilized to develop a nomogram for predicting meropenem-related thrombocytopenia. The Bootstrap method was conducted to internally validate the nomogram model. The discrimination, calibration, and clinical effectiveness of the model were assessed through the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).</p><p><strong>Results: </strong>A total of 625 patients were included in the training group. Among them, 73 patients experienced meropenem-related thrombocytopenia. Multivariate logistic regression analysis revealed that hypertension, baseline platelet count, and combined with cephalosporins or penicillins were independent risk factors for meropenem-related thrombocytopenia in patients with pulmonary infection. A risk prediction model was developed based on these four factors. The model demonstrated an AUC (area under the ROC curve) of 0.774 (95%CI: 0.718 ~ 0.829), with a sensitivity of 0.685 and a specificity of 0.737. The optimal critical value was determined to be 0.137. Internal validation yielded an AUC of 0.761, while external validation resulted in an AUC of 0.750 (95%CI: 0.702 ~ 0.799). The calibration diagram indicated a high level of agreement between the predicting and actual probabilities. Furthermore, the DCA demonstrated that the model had significant clinical benefit and practical value.</p><p><strong>Conclusion: </strong>A risk prediction model based on hypertension, baseline platelet count, combined with cephalosporins or penicillins could effectively predict the occurrence of meropenem-related thrombocytopenia in patients with pulmonary infection.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"127"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538264","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":"Alleviating effects of probiotic supplementation on biomarkers of inflammation and oxidative stress in non-communicable diseases: a systematic review and meta-analysis using the GRADE approach.","authors":"Xiaoyuan Yu, Li Yan, Lingxiao Chen, Xianmei Shen, Wenzheng Zhang","doi":"10.1186/s40360-025-00957-5","DOIUrl":"10.1186/s40360-025-00957-5","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and oxidative stress are key risk factors in noncommunicable diseases (NCDs). Probiotics have been suggested to be beneficial in mitigating inflammation and oxidative stress; however, the evidence remains inconsistent due to variations in study design, dosage, and patient populations.</p><p><strong>Methods: </strong>Studies were included following a systematic search of PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE, provided they fulfilled the eligibility criteria. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to clarify the effects of probiotics on oxidative stress and inflammation in non-communicable diseases (NCDs).</p><p><strong>Results: </strong>A review of 18 studies revealed that probiotic supplementation significantly reduced CRP (SMD = -1.33, 95% CI: -1.84, -0.82; p < 0.001, high certainty), TNF-α (SMD = -1.10, 95% CI: -1.66, -0.55; p < 0.001, low certainty), and MDA levels (SMD = -1.38, 95% CI: -2.08, -0.69; p < 0.001, high certainty). Additionally, while probiotics increased GSH levels (SMD = 0.65, 95% CI: 0.06, 1.23; p < 0.001, high certainty), they did not change the levels of IL-6 (SMD = -1.05, 95% CI: -2.21, 0.11; p < 0.001, low certainty), NO (SMD = 0.47, 95% CI: -0.54, 1.48; p = 0.363, low certainty) and TAC levels (SMD = 0.24, 95% CI: -0.27, 0.74; p = 0.357, moderate certainty).</p><p><strong>Conclusion: </strong>The supplementation of probiotics may have mitigated biomarkers associated with inflammation and oxidative stress.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"124"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538262","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":"Fosaprepitant for the prevention of multiple-day cisplatin chemotherapy-induced nausea and vomiting: a prospective randomized controlled study.","authors":"Lu Wang, Gaowa Jin, Wenjuan Wang, Jun Zhao, Feng Chen, Xiaorong Li, Ying Jiang, Zewei Zhang, Quanfu Li","doi":"10.1186/s40360-025-00964-6","DOIUrl":"10.1186/s40360-025-00964-6","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to compare the efficacy and safety of fosaprepitant plus triple therapy versus triple therapy alone, in terms of both routine and delayed regimen, in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving three-day cisplatin-based treatment.</p><p><strong>Methods: </strong>In a prospective randomized controlled trial, patients undergoing three-day cisplatin-based chemotherapy (25mg/m²/day) received fosaprepitant plus triple therapy or triple therapy alone on day 1 (routine regimen). For the evaluation of the delayed regimen, the administration of fosaprepitant and/or olanzapine was delayed for 1 day. Efficacy and safety in overall phase (OP) were evaluated within 5 days after initiation of chemotherapy.</p><p><strong>Results: </strong>Fosaprepitant plus triple therapy achieved a higher total protection (TP) rate during OP than triple therapy alone (56.9% vs. 40.4%; P = 0.018). Fosaprepitant plus triple therapy also produced a higher TP rate than triple therapy alone during delay phase (DP) (57.8% vs. 40.4%; P = 0.012) but not during acute phase (AP) (88.2% vs. 86.5%; P = 0.714). In addition, fosaprepitant plus triple therapy achieved higher complete response (CR) rates than triple therapy alone during DP, but not during AP. The delayed regimen appeared to have produced higher TP and CR rates than the routine regimen, but the differences were not statistically significant. The Kaplan-Meier curves showed that fosaprepitant plus triple therapy delayed the first vomiting.</p><p><strong>Conclusions: </strong>Fosaprepitant plus triple therapy demonstrated superiority over triple therapy alone for CINV control in patients receiving three-day cisplatin-based treatment.</p><p><strong>Clinical trials registration: </strong>This trial was registered in the China Clinical Trials Registry on December 8, 2020 (chiCTR2000040675).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"126"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538166","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 data analysis of montelukast in FDA Adverse Event Reporting System (FAERS) database.","authors":"Hesen Huang, Kaiqin Chen, Yu Du, Jing Gao, Yixian Ye, Wei Lin","doi":"10.1186/s40360-025-00959-3","DOIUrl":"10.1186/s40360-025-00959-3","url":null,"abstract":"<p><strong>Background: </strong>Montelukast(MTK) is a leukotriene receptor antagonist widely used clinically for treating asthma and rhinitis. However, many adverse events (AEs) have been reported. In this study, we aimed to investigate MTK's adverse drug reactions (ADRs) using real data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>We assessed the disproportionality of MTK-associated AEs by calculating metrics such as the ratio of reported ratios (ROR), proportional reporting ratios (PRR), Bayesian Belief Propagation Neural Networks (BCPNN), and Gamma-Poisson Shrinkers (GPS).</p><p><strong>Results: </strong>From 2004 to the third quarter of 2023, of the 20,340,254 case reports in the FAERS database, 86,732 MTK reports were recorded as \"principal suspect (PS)\" AEs.Disproportionate analyses identified 431 preferred terms (PTs) associated with MTK in 27 organ systems. Unexpected major AEs were noted, such as Suffocation feeling, Adrenal suppression, Sudden visual loss and Endocardial fibrosis, none of which were mentioned in the drug insert.</p><p><strong>Conclusion: </strong>Our findings are consistent with clinical observations highlighting potential new and unexpected ADR signals associated with MTK. Further prospective clinical studies are needed to confirm and elucidate the relationship between MTK and these ADRs. This study provides a fresh and unique perspective on the study of adverse drug events.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"130"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538261","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":"Methimazole-induced reproductive endocrine system disruption and hepatotoxicity: insights from a Trichogaster trichopterus animal model.","authors":"Mahdi Ahmadinia, Tahereh Naji, Homayoun Hosseinzadeh Sahafi","doi":"10.1186/s40360-025-00942-y","DOIUrl":"10.1186/s40360-025-00942-y","url":null,"abstract":"<p><strong>Background: </strong>Methimazole is commonly prescribed for managing hyperthyroidism, although concerns regarding its reproductive and hepatic adverse effects persist. This study aimed to evaluate the dose-dependent effects of methimazole on reproductive endocrine system function and hepatic integrity using an animal model.</p><p><strong>Methods: </strong>Adult female three-spot gourami (Trichogaster trichopterus) were administered intramuscular injections of methimazole at doses of 0.025, 0.05, and 0.1 mg/kg body weight every other day for 20 days. Gonadosomatic Index (GSI), Hepatosomatic Index (HSI), sex steroid hormones (17β-estradiol, testosterone, 17-hydroxyprogesterone), liver enzymes (GOT, GPT), and histological alterations in ovarian and hepatic histology were assessed.</p><p><strong>Results: </strong>Methimazole significantly reduced GSI in a dose-dependent manner, with the lowest value (3.33%, P < 0.05) observed at the highest dose. Although HSI increased slightly, differences among groups were not significant. Dose-dependent declines were observed in sex steroid hormones, with the most pronounced reduction at 0.1 mg/kg (P < 0.05), indicating significant disruption in steroidogenesis and ovarian function. Liver enzymes activity GOT and GPT were significantly elevated at doses of 0.05 and 0.1 mg/kg (P < 0.05), reflecting hepatic stress and potential hepatotoxicity. Histological analyses demonstrated significant disruption in ovarian follicle maturation, with oocytes arrested at early growth stages at higher methimazole doses. Furthermore, structural liver damage including hepatocyte hypertrophy, inflammation, and necrosis was observed at the highest methimazole dose.</p><p><strong>Conclusion: </strong>Methimazole induces notable reproductive and hepatic disturbances, highlighting the importance of monitoring endocrine and hepatic parameters during clinical methimazole therapy, especially in reproductive-age populations. These findings underscore the potential risks associated with methimazole treatment and suggest careful clinical monitoring to mitigate possible reproductive and hepatic adverse effects.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"128"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538167","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}