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Assessment of Rivaroxaban Plasma Concentration Using Chromogenic Anti-Xa Assays and UHPLC–MS/MS in Chinese Patients With Atrial Fibrillation 用显色抗xa法和UHPLC-MS /MS法评估中国房颤患者利伐沙班血药浓度
IF 3.3 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-30 DOI: 10.1111/bcpt.70088
Xiao-qin Liu, Yi Gu, Yu-fei Zhang, Wei Shen, Zhi-chun Gu, Ming-kang Zhong, Hong-yan Ding, Chun-lai Ma
{"title":"Assessment of Rivaroxaban Plasma Concentration Using Chromogenic Anti-Xa Assays and UHPLC–MS/MS in Chinese Patients With Atrial Fibrillation","authors":"Xiao-qin Liu,&nbsp;Yi Gu,&nbsp;Yu-fei Zhang,&nbsp;Wei Shen,&nbsp;Zhi-chun Gu,&nbsp;Ming-kang Zhong,&nbsp;Hong-yan Ding,&nbsp;Chun-lai Ma","doi":"10.1111/bcpt.70088","DOIUrl":"https://doi.org/10.1111/bcpt.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>Accurate quantification of rivaroxaban concentration is essential in some specific clinical situations. A prospective study was conducted to compare the rivaroxaban concentration measured by Zhenyuan anti-Xa assay with that by reference methods (ultrahigh performance liquid chromatography with tandem mass spectrometry [UHPLC–MS/MS] and Biophen DiXal) in 243 plasma samples from 182 patients with non-valvular atrial fibrillation. Zhenyuan anti-Xa assays demonstrated less bias versus reference methods in samples with concentrations exceeding 50 μg/L compared to those in the &lt; 50 μg/L group. Strong correlations were observed between Zhenyuan anti-Xa assays and both reference methods (Pearson's correlation coefficient 0.976 and 0.988, respectively). However, Bland–Altman analysis revealed systematic underestimation by Zhenyuan anti-Xa assays, with mean biases of 41.87 μg/L (vs. UHPLC–MS/MS) and 26.76 μg/L (vs. Biophen DiXal), particularly pronounced at higher levels. Rivaroxaban concentration in patients from clinical settings was with greater variability compared to the expected ranges. Patients taking underdose of rivaroxaban are more likely to have a trough concentration falling below the targeted therapeutic range.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Xiao-Jie-An Capsule Alleviates Uterine Fibroids by Modulating Oestrogen–Progesterone Balance and Reducing Inflammatory Response 小洁安胶囊通过调节雌激素-孕激素平衡和减少炎症反应来缓解子宫肌瘤
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-28 DOI: 10.1111/bcpt.70072
Yi Ying, Jihan Liu, Shanshan Ju, Meiyu Shen, Nannan Li, Yongpan An, Feng Lu, Yiwen Tang, Zhijing Wu, Baoxue Yang, Min Li
{"title":"Xiao-Jie-An Capsule Alleviates Uterine Fibroids by Modulating Oestrogen–Progesterone Balance and Reducing Inflammatory Response","authors":"Yi Ying,&nbsp;Jihan Liu,&nbsp;Shanshan Ju,&nbsp;Meiyu Shen,&nbsp;Nannan Li,&nbsp;Yongpan An,&nbsp;Feng Lu,&nbsp;Yiwen Tang,&nbsp;Zhijing Wu,&nbsp;Baoxue Yang,&nbsp;Min Li","doi":"10.1111/bcpt.70072","DOIUrl":"https://doi.org/10.1111/bcpt.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Uterine fibroids (UF) are benign tumours composed of smooth muscle cells and fibrous connective tissue. UF are common among women aged 30–50 years and often present with symptoms such as anaemia, pelvic pain and bladder dysfunction. Xiao-Jie-An Capsule (XJA), a traditional Chinese medicine formula, has been clinically used to treat UF. However, the underlying mechanisms of its efficacy remain unclear. The aim of this study was to determine the therapeutic effect of XJA and related mechanisms in a UF rat model. The experimental results showed that XJA significantly alleviated abnormalities in uterine morphology, tissue structure and purulent discharge in the UF rats. XJA also reduced serum oestrogen and progesterone in UF rats. Moreover, XJA decreased blood pro-inflammatory factors in UF rats by modulating the TLR4/NF-κB pathway. Western blotting and immunohistochemistry analyses revealed that XJA decreased the expression of Bcl-2, PCNA and Ki67 while increasing the expression of Bax, indicating its role in inhibiting cell proliferation and promoting apoptosis. Additionally, XJA exhibited immunomodulation in UF rats. In summary, our study suggests that XJA alleviates UF by multiple targets and mechanisms, such as restoring the oestrogen–progesterone balance, reducing inflammation, inhibiting cell proliferation, inducing apoptosis and regulating immune function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LW-AFC Protects Against Neurological and Neuropsychiatric Effects of SARS-CoV-2 Spike Protein in Mice LW-AFC保护小鼠免受SARS-CoV-2刺突蛋白的神经和神经精神作用
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-23 DOI: 10.1111/bcpt.70085
Wenyi Xiao, Jiao Wang, Jianhui Wang, Lu Han, Donghui Wei, Wenxia Zhou, Ning Jiang
{"title":"LW-AFC Protects Against Neurological and Neuropsychiatric Effects of SARS-CoV-2 Spike Protein in Mice","authors":"Wenyi Xiao,&nbsp;Jiao Wang,&nbsp;Jianhui Wang,&nbsp;Lu Han,&nbsp;Donghui Wei,&nbsp;Wenxia Zhou,&nbsp;Ning Jiang","doi":"10.1111/bcpt.70085","DOIUrl":"https://doi.org/10.1111/bcpt.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>Numerous clinical studies show that besides respiratory symptoms, COVID-19 patients frequently undergo neurological and neuropsychiatric problems. However, effective treatments for these problems remain insufficient. LW-AFC, derived from traditional Chinese medicine Liuwei Dihuang decoction, is effective in improving cognitive and mental dysfunctions in many animal models. In this study, we aimed to investigate the impact of SARS-CoV-2 spike protein on the mouse nervous system, evaluate the beneficial effects of LW-AFC, and explore its underlying mechanisms. After a single intranasal administration of spike protein, mice showed a significant decline in motor performance from week 1, and this decline persisted until week 32. Three weeks after administration, anxiety-like behaviors and spatial memory deficits appeared but returned to normal by week 32. It is suggested that spike protein causes dynamic neurological and psychiatric impairments in mice, which is consistent with clinical findings. LW-AFC reversed these effects, enhancing motor performance, improving spatial memory, and alleviating anxiety. LW-AFC increased the number of NeuN-positive cells and decreased the number of Iba-1-positive cells. Additionally, LW-AFC reduced the levels of pro-inflammatory cytokines IL-6 and TNF-α, increased ATP levels, and enhanced the activity of mitochondrial respiratory chain complex I. These findings indicate that LW-AFC holds great potential as a therapeutic option for SARS-CoV-2-induced neuropsychiatric impairments.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Triterpenoid From Persimmon Leaves (Diospyros kaki L.f.) Exerted Anti–Type 2 Diabetic Effects and No Toxicity in Experimental Animals 柿叶中的三萜(Diospyros kaki L.f.)对实验动物有抗2型糖尿病作用且无毒性
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-23 DOI: 10.1111/bcpt.70081
Hung Van Nguyen, Ha Thu Thi Nguyen, Nhan Trong Le, Trang Quynh Tran, Loan Thanh Thi Nguyen, Thanh Phuong Mai, Phong Xuan Pham, Anh Van Thi Pham, Hoai Thi Nguyen
{"title":"Triterpenoid From Persimmon Leaves (Diospyros kaki L.f.) Exerted Anti–Type 2 Diabetic Effects and No Toxicity in Experimental Animals","authors":"Hung Van Nguyen,&nbsp;Ha Thu Thi Nguyen,&nbsp;Nhan Trong Le,&nbsp;Trang Quynh Tran,&nbsp;Loan Thanh Thi Nguyen,&nbsp;Thanh Phuong Mai,&nbsp;Phong Xuan Pham,&nbsp;Anh Van Thi Pham,&nbsp;Hoai Thi Nguyen","doi":"10.1111/bcpt.70081","DOIUrl":"https://doi.org/10.1111/bcpt.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>The acute and subchronic toxicity, along with the anti–type 2 diabetic effects, of a triterpenoid extract from persimmon leaves (Tri DKL) was evaluated in animals. Acute oral toxicity was assessed in <i>Swiss</i> mice, whereas subchronic toxicity was investigated in <i>Wistar</i> rats given Tri DKL at 125 and 375 mg/kg body weight (BW) daily for 90 days. Type 2 diabetes was induced in <i>Swiss</i> mice via an 8-week high-fat diet, followed by a single intraperitoneal injection of streptozotocin (100 mg/kg BW). Diabetic mice were subsequently treated with Tri DKL at 250 and 750 mg/kg BW/day for 2 weeks. Results showed that Tri DKL, even at the highest dose of 2500 mg/kg, did not produce any signs of acute toxicity in mice. In rats, subchronic administration of 125 and 375 mg/kg BW/day caused no significant alterations in general behaviours, haematological parameters or hepatic/renal function markers. In diabetic mice, Tri DKL significantly reduced blood glucose levels at both doses. It also lowered total cholesterol and hepatic malondialdehyde levels. Notably, at 250 mg/kg BW/day, Tri DKL decreased triglyceride levels while improving liver and pancreatic tissue histology. Overall, Tri DKL exhibited no acute or subchronic toxicity in animals and demonstrated hypoglycemic and lipid-lowering effects in type 2 diabetic mice, suggesting potential therapeutic benefits.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Hydroxychloroquine in the Management of Rheumatic Disorders: A Comprehensive Review 羟氯喹在风湿病治疗中的作用:综述
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-22 DOI: 10.1111/bcpt.70082
Ilker Ates, Hilal Sahin, Lalu Muhammad Irham, Serkan Yilmaz, Sinan Suzen
{"title":"The Role of Hydroxychloroquine in the Management of Rheumatic Disorders: A Comprehensive Review","authors":"Ilker Ates,&nbsp;Hilal Sahin,&nbsp;Lalu Muhammad Irham,&nbsp;Serkan Yilmaz,&nbsp;Sinan Suzen","doi":"10.1111/bcpt.70082","DOIUrl":"https://doi.org/10.1111/bcpt.70082","url":null,"abstract":"<p>A drug preferred for its antimalarial effect called hydroxychloroquine (HCQ) has long been used to manage and avoid malaria. Nevertheless, its exact mode of action is still unknown. HCQ works through a variety of strategies to influence distinct molecular and cellular pathways. Additionally, HCQ has been demonstrated to be an effective treatment for rheumatic conditions such as primary Sjögren's syndrome, rheumatoid arthritis, antiphospholipid syndrome and systemic lupus erythematosus. Despite being widely regarded as safe, HCQ has been known to cause adverse responses; thus, doctors should closely evaluate rheumatism patients before taking these medications. The current study aims to emphasize the potential side effects of treatment while supporting the clinical usage of HCQ for autoimmune disorders.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Huoxin Pill Ameliorates Atrial Fibrillation by Modulating Autonomic Nervous Balance and Electrical Conduction Heterogeneity: Insights From Systems Pharmacology and Experimental Validation 火心丸通过调节自主神经平衡和电传导异质性改善心房颤动:来自系统药理学和实验验证的见解
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-22 DOI: 10.1111/bcpt.70079
Mimi Huang, Lingli Wang, Zejun Xu, Chenxing Huang, Sisi He, Yiqiu Liao, Jiaxuan Li, Fei Qin, Yongjun Chen, Qiqi Zhang, Hongjun Yang, Dongyan Liu, Taiyi Wang
{"title":"Huoxin Pill Ameliorates Atrial Fibrillation by Modulating Autonomic Nervous Balance and Electrical Conduction Heterogeneity: Insights From Systems Pharmacology and Experimental Validation","authors":"Mimi Huang,&nbsp;Lingli Wang,&nbsp;Zejun Xu,&nbsp;Chenxing Huang,&nbsp;Sisi He,&nbsp;Yiqiu Liao,&nbsp;Jiaxuan Li,&nbsp;Fei Qin,&nbsp;Yongjun Chen,&nbsp;Qiqi Zhang,&nbsp;Hongjun Yang,&nbsp;Dongyan Liu,&nbsp;Taiyi Wang","doi":"10.1111/bcpt.70079","DOIUrl":"https://doi.org/10.1111/bcpt.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Huoxin Pill (HXP), a traditional Chinese medicine for cardiovascular diseases, demonstrates clinically reported anti-atrial fibrillation (AF) effects, though its mechanisms remain unclear. To investigate these mechanisms, we established an acetylcholine-calcium chloride (ACh-CaCl<sub>2</sub>)-induced AF model in rats divided into control, AF, HXP (HXP-L: 3.33; HXP-M: 10; HXP-H: 30 mg/kg) and verapamil (25 mg/kg) groups. Following daily modelling, treatments were administered via gavage from Days 4 to 10. Electrocardiography (ECG) subsequently assessed AF susceptibility while echocardiography evaluated cardiac function. Systems pharmacology predicted HXP's targets/pathways for AF amelioration, with heart rate variability (HRV) and nerve activity recording examining autonomic balance. Electrical mapping quantified activation time (AT), conduction velocity (CV), conduction dispersion and effective refractory period (ERP) in isolated hearts. Results demonstrated that the AF group exhibited increased AF incidence/duration and decreased left ventricular ejection fraction/fractional shortening (LVEF/LVFS). Systems pharmacology revealed significant enrichment in cardiovascular pathways (including AF), while HRV and nerve recording indicated autonomic imbalance. Isolated AF hearts showed prolonged AT, slowed CV, increased conduction dispersion and shortened ERP. HXP significantly ameliorated these alterations. In conclusion, these findings suggest that HXP improves ACh-CaCl<sub>2</sub>-induced AF, potentially through modulating autonomic nervous balance and atrial electrical conduction heterogeneity.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood Pressure–Lowering Effects of Aldosterone Synthase Inhibitors—A Systematic Review 醛固酮合成酶抑制剂降血压作用的系统综述
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-22 DOI: 10.1111/bcpt.70080
Anders Almskou Rasmussen, Ketil Lehm Nordestgaard, Ulf Simonsen, Niels Henrik Buus
{"title":"Blood Pressure–Lowering Effects of Aldosterone Synthase Inhibitors—A Systematic Review","authors":"Anders Almskou Rasmussen,&nbsp;Ketil Lehm Nordestgaard,&nbsp;Ulf Simonsen,&nbsp;Niels Henrik Buus","doi":"10.1111/bcpt.70080","DOIUrl":"https://doi.org/10.1111/bcpt.70080","url":null,"abstract":"<p>Excess aldosterone production contributes to the development of hypertension and results in fibrosis with dysfunction of the heart, vasculature and kidneys. Consequently, new agents have been developed to reduce endogenous aldosterone synthesis. The primary objective of this systematic review is to describe the BP-lowering effects of aldosterone synthase inhibitors (ASIs) in hypertensive patients and, secondly, to describe their potential renal protective effects and possible influence on cortisol production and plasma potassium. We searched PubMed, Embase and ClinicalTrials.gov and included randomized controlled and clinical trials according to PICO using the review tool Covidence. Thirteen studies were included and all demonstrated BP reduction through ASI treatment. Among patients with apparent resistant hypertension, the placebo-corrected reductions in seated systolic BP were 11.0 mmHg for baxdrostat and 9.6 mmHg for lorundrostat. A significant suppression of cortisol production was found for LCI699 (osilodrostat) but not for baxdrostat, lorundrostat, BI 690517 (vicadrostat) or dexfadrostat. Studies on BI 690517 showed a reduction in urine–albumin–creatinine ratio, indicating renal protection. ASIs may increase potassium levels. We conclude that ASIs have promising BP-lowering effects with very limited effects on cortisol production and offer reno-protective effects in chronic kidney disease. Studies on hypertensive target organ damage and cardiovascular outcomes are, however, lacking.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antioxidant, Antiinflammatory and Antiapoptotic Effects of Lycopene in Rats With Vancomycin-Induced Nephrotoxicity 番茄红素对万古霉素肾毒性大鼠的抗氧化、抗炎和抗凋亡作用
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-21 DOI: 10.1111/bcpt.70084
Hülya Demirkapı Atik, Orkun Atik, Recep Aslan, Yavuz Osman Birdane, Abdullah Eryavuz
{"title":"Antioxidant, Antiinflammatory and Antiapoptotic Effects of Lycopene in Rats With Vancomycin-Induced Nephrotoxicity","authors":"Hülya Demirkapı Atik,&nbsp;Orkun Atik,&nbsp;Recep Aslan,&nbsp;Yavuz Osman Birdane,&nbsp;Abdullah Eryavuz","doi":"10.1111/bcpt.70084","DOIUrl":"https://doi.org/10.1111/bcpt.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The most important side effect of vancomycin (Vanco) is nephrotoxicity (NPT). Lycopene (Lyco) has been reported to have anti-inflammatory and anti-apoptotic properties in addition to its antioxidant activity. The aim is to investigate the protective efficacy of Lyco against the NPT condition that limits the use of Vanco.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A total of 48 rats were used in the study in six groups of eight rats each, namely, Corn Oil Control, Lyco 5, Lyco 10, Vanco, Vanco + Lyco 5 and Vanco + Lyco 10.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vanco (400 mg/kg, intraperitoneal) administered for 7 days elevated serum BUN, creatinine, uric acid levels and renal lipid peroxidation while decreasing renal GSH and the activity of the antioxidant enzymes SOD, CAT and GPx. Vanco also increased the levels of inflammatory markers NF-κB, TNF-<i>α</i>, Bcl-3 and p38<i>α</i> MAPK activity. It decreased the level of AQP-1 and increased the level of NGAL. In addition, it activated apoptosis by decreasing Bcl-2 and Procas-3 expression levels while increasing apoptotic p53, Bax and Cyt-c expression levels. Lyco treatment at both doses (5 and 10 mg/kg, orally) ameliorated NPT by reducing oxidative stress, inflammation and apoptosis, while the higher dose was more effective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings showed that Lyco attenuated Vanco-induced NPT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and Safety of Clopidogrel With and Without a Proton Pump Inhibitor: A Systematic Review and Meta-Analysis 氯吡格雷加质子泵抑制剂和不加质子泵抑制剂的疗效和安全性:一项系统综述和荟萃分析
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-21 DOI: 10.1111/bcpt.70087
Magnus A. B. Axelsson, Naldy Parodi López, Eva Wikström Jonsson, Susanna M. Wallerstedt
{"title":"Efficacy and Safety of Clopidogrel With and Without a Proton Pump Inhibitor: A Systematic Review and Meta-Analysis","authors":"Magnus A. B. Axelsson,&nbsp;Naldy Parodi López,&nbsp;Eva Wikström Jonsson,&nbsp;Susanna M. Wallerstedt","doi":"10.1111/bcpt.70087","DOIUrl":"https://doi.org/10.1111/bcpt.70087","url":null,"abstract":"<p>Classifications of drug interaction alerts regarding clopidogrel and a proton pump inhibitor (PPI) differ between knowledge resources. In this systematic review, Medline, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) applying PICO criteria: P = patients on clopidogrel; I = intervention: PPI (subgroup: [es]omeprazole); C = comparison: no PPI (C1) or a PPI other than (es)omeprazole (C2); O = outcomes, main: a composite of cardiovascular events (efficacy); also: overt gastrointestinal bleeding (safety). Fourteen RCTs fulfilled the PICO criteria, five without high risk of bias and with at least one clinical event per study arm. Regarding efficacy with or without a PPI, the pooled risk ratio (RR) and risk difference (RD) were 1.08 (95% confidence interval (CI) 0.78; 1.50) and 0.2 percentage points (95% CI −0.9; 1.2), respectively (four RCTs; 4341 patients [96% also used aspirin, 98% receiving I used (es)omeprazole]; moderate certainty evidence). Regarding safety, the RR and RD were 0.13 (95% CI 0.03; 0.59) and −0.7 percentage points (95% CI −1.1; −0.3), respectively (one RCT; 3761 patients; moderate certainty evidence). The available evidence did not allow conclusions regarding omeprazole versus pantoprazole. In conclusion, concurrent use of a PPI probably does not largely affect clopidogrel efficacy, but probably reduces the risk of overt gastrointestinal bleeding.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated With Mebendazole Use 美苯达唑与史蒂文斯-约翰逊综合征和中毒性表皮坏死松解相关的风险
IF 2.7 4区 医学
Basic & Clinical Pharmacology & Toxicology Pub Date : 2025-07-15 DOI: 10.1111/bcpt.70086
Ida M. Heerfordt, Espen Jimenez-Solem, Magnus Middelboe, Rasmus Huan Olsen, Henrik Horwitz
{"title":"Risk of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated With Mebendazole Use","authors":"Ida M. Heerfordt,&nbsp;Espen Jimenez-Solem,&nbsp;Magnus Middelboe,&nbsp;Rasmus Huan Olsen,&nbsp;Henrik Horwitz","doi":"10.1111/bcpt.70086","DOIUrl":"https://doi.org/10.1111/bcpt.70086","url":null,"abstract":"&lt;p&gt;Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially fatal conditions, most often caused by adverse reactions to medication [&lt;span&gt;1&lt;/span&gt;]. They are characterized by widespread skin necrosis and detachment of the epidermis [&lt;span&gt;1&lt;/span&gt;]. The conditions are considered part of a disease spectrum, differentiated primarily by the extent of skin involvement [&lt;span&gt;1&lt;/span&gt;]. It is accepted that the triggering medication is generally used within 3 months before symptom onset [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Mebendazole, a commonly used anthelmintic in both children and adults, has rarely been associated with SJS and TEN, primarily through isolated case series [&lt;span&gt;2&lt;/span&gt;]. Mebendazole acts by binding to a subunit of helminthic tubulin, inhibiting microtubule formation and thereby disrupting essential cellular processes [&lt;span&gt;3&lt;/span&gt;]. While patient labels for mebendazole cite occurrences of SJS and TEN as rare, listed as occurring in between 1 in 10 000 and 1 in 1000 treatments, the actual risk has not been quantified in large-scale, population-based studies [&lt;span&gt;2, 4-6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;This study aimed to quantify the risk of developing SJS and TEN associated with mebendazole usage, to alleviate fears and improve the clinical basis for rational decision-making in prescribing.&lt;/p&gt;&lt;p&gt;This study employed a nationwide, population-based design using the Danish National Health Registries [&lt;span&gt;7&lt;/span&gt;]. All Danish residents are systematically registered in the Danish Civil Registration System with a unique personal identification number, enabling precise linkage across health registries [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;First, we established a cohort consisting of the entire Danish population from 1994 to 2025. Using the Danish National Prescription Register [&lt;span&gt;7&lt;/span&gt;], we identified all individuals who redeemed at least one prescription for mebendazole (Anatomical Therapeutic Chemical (ATC) code P02CA01). The Danish National Patient Register was used to identify all cases of first-time diagnosis of erythema multiforme bullosum/SJS (International Classification of Diseases, 10th Revision (ICD-10) code L51.1) or TEN (ICD-10 code L51.2) during the same period. Patients assigned both diagnoses were included on equal terms with those assigned only one diagnosis. Based on this cohort, we calculated the absolute frequency of SJS/TEN following mebendazole use.&lt;/p&gt;&lt;p&gt;Second, we conducted a nested case–control study within the same cohort. All individuals with a first-time diagnosis of SJS or TEN were identified as cases. For each case, 100 controls were selected using risk set sampling, matched on age, sex and index date, based on data from the Danish Civil Registration System. Participants were required to have been residents in Denmark for at least 1 year prior to the index date. Mebendazole prescription retrieval was assessed for both cases and controls during two exposure windows: within 3 months and within 12 months b","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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