Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Effectiveness of Botulinum Toxin A Injection for Hemiplegic Shoulder Pain: A Meta-Analysis of Randomized Controlled Trials","authors":"Qian Li,&nbsp;Hongge Shi,&nbsp;Liping Jia,&nbsp;Lichao Liang","doi":"10.1111/bcpt.70043","DOIUrl":"https://doi.org/10.1111/bcpt.70043","url":null,"abstract":"<div>\u0000 \u0000 <p>Hemiplegic shoulder pain (HSP) is a common post-stroke complication impairing function and quality of life. Botulinum toxin A (BTA), a neurotoxin that inhibits acetylcholine release and reduces spasticity, has been proposed for treating HSP, though its clinical effectiveness remains unclear. This meta-analysis aimed to evaluate BTA's efficacy in managing HSP. Nine randomized controlled trials involving 272 patients were included. Compared to placebo, BTA significantly reduced pain at 1 week (SMD = −0.93; 95% CI [−1.67, −0.19]; <i>p</i> = 0.01) and 4 weeks (SMD = −0.90; 95% CI [−1.51, −0.28]; <i>p</i> &lt; 0.01), but not at 12 weeks. External rotation ROM improved at all time points, peaking at 4 weeks (WMD = 6.20; 95% CI [3.11, 9.30]; <i>p</i> &lt; 0.01). Abduction ROM improved at 4 and 12 weeks. Spasticity decreased significantly throughout, with the largest reduction at 12 weeks (WMD = −0.78; 95% CI [−1.42, −0.14]; <i>p</i> = 0.02). Functional gains were noted at 4 weeks. However, these results should be interpreted cautiously due to small samples and heterogeneous injection protocols across studies. In conclusion, BTA is effective for short-term HSP management, particularly in relieving pain and improving motor function. Further large-scale trials with standardized methods are needed.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883987","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}

{"title":"Traditional Chinese Medicine for Inhibiting Ferroptosis in Ischemic-Related Diseases","authors":"Yukun Zhang,&nbsp;Yang Yao,&nbsp;Qiaoling Zhang,&nbsp;Baoxue Yang","doi":"10.1111/bcpt.70039","DOIUrl":"https://doi.org/10.1111/bcpt.70039","url":null,"abstract":"<p>Ischemic-related diseases, such as myocardial infarction and stroke, are primarily driven by a deficit in oxygen supply leading to cellular damage and death. Ferroptosis has emerged as an important mechanism contributing to the progression of ischemic injury, characterized by iron-dependent lipid peroxidation. This review aims to provide a comprehensive overview of the significant mechanisms underlying ferroptosis in ischemic conditions and explores the potential effects of traditional Chinese medicines (TCMs) and their extracts. Numerous compounds extracted from TCMs, including flavonoids, polyphenols and terpenes, exhibit potent antiferroptotic effects by activating nuclear factor erythroid 2–related factor 2, upregulating glutathione peroxidase 4, inhibiting lipid peroxidation and so on. These properties render TCMs a promising candidate for developing novel ferroptosis therapeutic strategies. This review underscores the importance of investigating the interactions between ferroptosis and TCMs within the context of ischemic diseases. These findings provide valuable insights for future research to identify targets associated with ferroptosis regulation, thereby expanding the pharmacological perspective of TCMs in treating ischemic diseases and revealing the potential of novel therapeutic strategies. Additionally, this highlights the relevance of integrating traditional and modern medical approaches in addressing complex health issues.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883818","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}

{"title":"Trends in Postoperative Opioid Use in Norway 2011–2018: A Nationwide Registry-Based Study","authors":"Per-Jostein Samuelsen,&nbsp;Vidar Hjellvik,&nbsp;Ingvild Odsbu,&nbsp;Audun Stubhaug,&nbsp;Svetlana Skurtveit,&nbsp;Sara Magelssen Vambheim","doi":"10.1111/bcpt.70040","DOIUrl":"https://doi.org/10.1111/bcpt.70040","url":null,"abstract":"<div>\u0000 \u0000 <p>Little is known about the overall trends in postoperative opioid use in a Nordic setting. We investigated the trends in Norway between 2011 and 2018. We linked the Norwegian Prescription Database, the Norwegian Patient Registry, the Cancer Registry of Norway and the Cause of Death Registry. Postoperative opioid use was defined as the first opioid dispensing per year within 14 days of a NOMESCO Classification of Surgical Procedure code. We excluded patients with cancer or opioid maintenance therapy. We calculated period prevalence (Norwegian population ≥ 15 years as the denominator), substance distribution, initial amount and proportion of long-acting formulations. Among 746 435 postoperative opioid users ≥ 15 years, the period prevalence increased from 27.0/1000 in 2011 to 30.0/1000 in 2018 (long-term use: 2.0 to 3.3/1000). Codeine was most frequent (67%) in 2011, while codeine and tramadol were equally dispensed (41% and 43%) in 2018; oxycodone increased from 3% to 12%. The initial amount increased for opioids as a group but declined for oxycodone (1236 morphine milligram equivalents [MME]/patient to 914 MME/patient) and tramadol (233 MME/patient to 219 MME/patient). Long-acting depot formulations increased from 5% to 12%. Over time, postoperative opioid use increased, with a shift toward more tramadol and oxycodone in lower initial amounts, and increased use of long-acting formulations.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879863","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}

{"title":"Capillary Sampling Enables Venetoclax Concentration Measurement in Acute Myeloid Leukaemia Within Academic Multicentre Trial","authors":"Sari Kytölä,&nbsp;Mika Kurkela,&nbsp;Johanna I. Kiiski,&nbsp;Ida Vänttinen,&nbsp;Tanja Ruokoranta,&nbsp;Anu Partanen,&nbsp;Annasofia Holopainen,&nbsp;Marja Pyörälä,&nbsp;Milla E. L. Kuusisto,&nbsp;Timo Siitonen,&nbsp;Sirpa Koskela,&nbsp;Johanna Rimpiläinen,&nbsp;Pia Ettala,&nbsp;Heikki Kuusanmäki,&nbsp;Mikko Niemi,&nbsp;Janne T. Backman,&nbsp;Mika Kontro","doi":"10.1111/bcpt.70041","DOIUrl":"https://doi.org/10.1111/bcpt.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>Venetoclax has improved outcomes for acute myeloid leukaemia (AML) patients unfit for intensive chemotherapy. Managing cytopenias and infections remains challenging. Previous pharmacokinetic studies have shown considerable variability in venetoclax concentrations between individuals; however, data regarding whether higher levels increase toxicity or impact efficacy are limited. This study assessed the feasibility of using fingertip capillary blood plasma, collected via microsampling, to measure venetoclax trough concentrations and explored their association with toxicity and treatment outcomes. Concentrations were measured during the first two therapy cycles in 89 patients with newly diagnosed or relapsed or refractory AML receiving azacitidine and venetoclax. Validation with 37 parallel venipuncture and capillary samples showed excellent correlation (<i>R</i>² of 0.835, <i>p</i> &lt; 0.0001). No significant associations were found between venetoclax concentrations and patient characteristics such as gender, age and weight. While no statistically significant effects on therapy outcomes or adverse events were identified, trends suggested lower concentrations in refractory patients and higher in those with morphologic leukaemia free state or extended cycle length. Additionally, three separate <i>CYP3A4</i> and <i>CYP3A5</i> single-nucleotide polymorphisms were analysed in 81 patients for their potential impact on venetoclax concentrations. This study demonstrates that the capillary blood plasma method is viable for measuring venetoclax levels.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879865","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}

{"title":"Gentiopicroside Attenuated Dopaminergic Neurodegeneration via Inhibiting Neuroinflammatory Responses and Ferroptosis in Experimental Models of Parkinson's Disease","authors":"Fangling Sun,&nbsp;Yifu Ma,&nbsp;Dan Li,&nbsp;Qianqian Yang,&nbsp;Tingwei Yuan,&nbsp;Tingting Liu,&nbsp;Xin Tian,&nbsp;Zixin Zhu,&nbsp;Wenrong Zheng,&nbsp;Yufeng Wang,&nbsp;Wen Wang","doi":"10.1111/bcpt.70036","DOIUrl":"https://doi.org/10.1111/bcpt.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Along with the hallmark of α-synuclein deposition, neuroinflammation and iron accumulation have emerged as essential pathological features for dopaminergic neuron degeneration in PD patients and animal models. Preclinical studies have highlighted gentiopicroside's anti-inflammatory activities in treating arthritis, colitis and pancreatitis, and its neuroprotective effects on neurological diseases such as <span>AD</span>, chronic neuropathic pain and ischemia. However, the effects and mechanisms of gentiopicroside on PD-related conditions remain uncertain. Here, we evaluated the potential benefits of gentiopicroside using a unilateral 6-OHDA rat model and a MPP⁺-induced cell model. Our findings indicated that gentiopicroside improved motor deficits and restored nigral TH-positive neurons in vivo. Mechanistically, gentiopicroside ameliorated inflammatory responses of 6-OHDA-induced rats, decreased NF-κB and pro-inflammatory cytokines levels and reduced Iba-1-positive microglia in the substantia nigra. Furthermore, gentiopicroside regulated the levels of DMT1 and FPN1, thereby inhibiting iron accumulation in PD rats. In vitro, gentiopicroside preserved the viability of MPP⁺-treated SH-SY5Y cells and suppressed NF-κB activity and its downstream factors' levels. Meanwhile, gentiopicroside inhibited lipid peroxidation and ROS production, while it upregulated the expression of GPX4 in MPP⁺-treated cells. And these antiferroptosis effects were also linked to iron transporters regulation. Conclusively, gentiopicroside exhibits neuroprotective effects via alleviating neuroinflammation and iron-dependent ferroptosis, offering promise for PD treatment.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852948","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}

{"title":"High Throughput Pharmacovigilance Screening for Roflumilast Adverse Effects in Real-World Settings: A Sequence Symmetry Analysis","authors":"Abdullah Abdelaziz,&nbsp;Charles E. Gaber,&nbsp;Preeti Gupta,&nbsp;Todd A. Lee","doi":"10.1111/bcpt.70038","DOIUrl":"https://doi.org/10.1111/bcpt.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Roflumilast is an add-on therapy for COPD following exacerbations, but real-world safety data in the United States are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to identify safety signals associated with roflumilast initiation through a high-throughput signal detection algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using sequence symmetry analysis (SSA), we analysed Marketscan databases for new roflumilast users (2011–2021). We screened for adverse effects across 211 therapeutic classes within 365 days of initiation. Sensitivity analyses were conducted by sex, age and observation period. Crude and adjusted sequence ratios (cSR and aSR) were reported with 95% confidence intervals (CIs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 11 091 patients (53% aged 65+, 52% female), 32 safety signals were identified. Strong associations were observed with antithyroid agents (aSR, 4.18; 95% CI: 1.66–11.95), parathyroid hormones (aSR, 3.09; 95% CI: 1.56–6.44), haematopoietic agents (aSR, 2.55; 95% CI: 1.07–6.49) and meglitinides (aSR, 2.37; 95% CI: 1.15–5.35). While many signals aligned with prior clinical trial data, novel associations with antithyroid and parathyroid agents were discovered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In our study, we detected 32 safety signals for roflumilast, including notable associations with antithyroid agents and parathyroid hormones. Future investigations using more robust study designs are warranted to evaluate those signals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852947","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}

{"title":"Alterations in the Plasma Metabolome Associated With Maternal Smoking During the First Trimester and Foetal Growth","authors":"Wadzanai Masvosva,&nbsp;Taija Voutilainen,&nbsp;Marko Lehtonen,&nbsp;Retu Haikonen,&nbsp;Seppo Auriola,&nbsp;Leea Keski-Nisula,&nbsp;Jaana Rysä,&nbsp;Olli Kärkkäinen","doi":"10.1111/bcpt.70037","DOIUrl":"https://doi.org/10.1111/bcpt.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Tobacco smoking during pregnancy has been associated with an increased risk of adverse outcomes like low birth weight. This study determined changes in the circulating metabolome linked to maternal smoking in the first trimester and correlated these changes to the growth of the foetus. The circulating metabolome was examined from first trimester plasma samples by non-targeted (global) liquid chromatography mass spectrometry-based metabolite profiling of 227 pregnant women (99 smokers and 117 non-smokers) from the Kuopio Birth Cohort Study. Tobacco smoking was self-reported through a questionnaire and verified with cotinine measurements from plasma samples. In summary, 64 significant differences were observed between the groups after correction for multiple testing e.g. in metabolites indicating endocrine disruption (e.g. dehydroepiandrosterone sulphate [DHEA-S], VIP = 2.70, <i>d</i> = 0.68, <i>p</i> &lt; 0.0001), metabolites associated with oxidative stress (e.g. bilirubin, VIP = 2.00, <i>d</i> = 0.50, <i>p</i> &lt; 0.0001) and lipid metabolism (e.g. LysoPC 16:1, VIP = 2.07, <i>d</i> = 0.51, <i>p</i> &lt; 0.0001). Some of these metabolites, e.g. DHEA-S and bilirubin, correlated with low birth weight, and some, e.g. LysoPC 16:1, correlated with small head circumference at birth. In conclusion, maternal smoking during the first trimester of pregnancy was associated with an altered metabolite profile linked to endocrine disruption and increased oxidative stress.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826894","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}

{"title":"Montelukast Induces Depressive-Like Behaviour in ICR Young Mice Through Oxidative Stress and Inflammatory Response","authors":"Shalawate Ayijiang,&nbsp;Murezati Tiliwaerde,&nbsp;Yaqi Yang,&nbsp;Yanlin Li,&nbsp;Huan Gao,&nbsp;Jingyi Jia,&nbsp;Shen Wang,&nbsp;Qi Liu,&nbsp;Zengliang Jin","doi":"10.1111/bcpt.70033","DOIUrl":"https://doi.org/10.1111/bcpt.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In response to the US Food and Drug Administration's black box warning highlighting the neuropsychiatric risks associated with montelukast, the mechanisms underlying these psychiatric adverse effects, particularly depression in paediatric populations, have remained poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this, we examined whether montelukast induces depression-like behaviours in an animal model and investigated the potential mechanisms. Young ICR mice were administered montelukast continuously for 28 days, and depression-like behaviours were assessed using the open field test (OFT), tail suspension test (TST), and forced swim test (FST). Oxidative stress and inflammatory markers were analysed via RT-qPCR, biochemical assays and western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results revealed that 24 h post-montelukast administration, cysteinyl leukotriene receptor 1 and malondialdehyde (MDA) levels were significantly upregulated in the hippocampus, while glutathione (GSH), glutathione peroxidase 4 (GPx4), superoxide dismutase 2 (SOD2) and catalase (CAT) levels were downregulated. After 28 days of treatment, MDA levels remained elevated, and GSH, GPx4, SOD2 and CAT levels were further reduced. Additionally, hippocampal interleukin-1β and serum corticosterone levels were increased, whereas hippocampal glucocorticoid receptor expression was decreased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings collectively demonstrate that montelukast induces depression-like behaviours in young ICR mice through mechanisms involving enhanced oxidative stress and inflammatory responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818631","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}

{"title":"Exploring Retene's Tumour-Initiating Potential: Integrating Computational and Experimental Approaches","authors":"Francisco Carlos da Silva Junior,&nbsp;Thiago Pires Cláudio,&nbsp;Ricardo Luiz Cavalcanti de Albuquerque-Júnior,&nbsp;Silvia Regina Batistuzzo de Medeiros","doi":"10.1111/bcpt.70034","DOIUrl":"https://doi.org/10.1111/bcpt.70034","url":null,"abstract":"&lt;p&gt;Currently, the US Environmental Protection Agency (EPA) classifies 16 PAHs as priority pollutants, including seven carcinogenic compounds [&lt;span&gt;1&lt;/span&gt;]. Nevertheless, numerous nonlisted PAHs may also contribute to carcinogenic effects, including Benzo[&lt;i&gt;a&lt;/i&gt;]pyrene (B[&lt;i&gt;a&lt;/i&gt;]P) and dibenzo[&lt;i&gt;a,h&lt;/i&gt;]anthracene [&lt;span&gt;2&lt;/span&gt;]. Retene (RET, 1-methyl-7-isopropylphenanthrene) is a polycyclic aromatic hydrocarbon (PAH) primarily formed during the combustion of coniferous wood and is a significant component of atmospheric particulate matter from forest fires [&lt;span&gt;3, 4&lt;/span&gt;]. Metabolic and mechanistic studies suggest that RET induces genotoxicity and chromosomal alterations through oxidative stress [&lt;span&gt;3&lt;/span&gt;], raising concerns about its potential carcinogenicity. Although RET is structurally similar to well-known carcinogenic PAHs, its toxicological risks remain poorly investigated.&lt;/p&gt;&lt;p&gt;Structure–activity relationship (SAR) models and in vivo studies are widely used to predict toxicity and assess carcinogenic potential [&lt;span&gt;5&lt;/span&gt;]. PAHs are known to induce skin carcinogenesis via metabolic activation in dermal models [&lt;span&gt;6&lt;/span&gt;], highlighting the relevance of such approaches. Given the limited data on RET's carcinogenic effects, this study aims to evaluate its tumour-initiating potential using SAR predictions and an in vivo Swiss albino mouse model. To our knowledge, no previous studies have explored RET's involvement in carcinogenesis, and our findings could help clarify its underestimated toxicological impact.&lt;/p&gt;&lt;p&gt;According to Danish(Q)SAR calibrated for Syrian hamster embryo (SHE) cells (Table 1), RET, B[&lt;i&gt;a&lt;/i&gt;]P and DMBA showed positive results for malignant transformation. Furthermore, structural alerts of the type &lt;i&gt;genotoxic carcinogenicity&lt;/i&gt; were detected for all PAHs investigated using ToxTree (Table 1). Moreover, when organ-specific carcinogenicity was analysed using the ROSC-Pred calibrated for rodents, RET, B[&lt;i&gt;a&lt;/i&gt;]P and DMBA were predicted to induce tumours in different organs or tissues, such as skin, lung, liver, and kidney (Supporting Information S2).&lt;/p&gt;&lt;p&gt;The compounds RET, B[&lt;i&gt;a&lt;/i&gt;]P and DMBA did not induce changes in body weight (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;6,34&lt;/sub&gt; = 1.203, &lt;i&gt;p&lt;/i&gt; = 0.32) or increase mortality (&lt;i&gt;p&lt;/i&gt; &gt; 0.42) (Supporting Information S3). Water (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;15,90&lt;/sub&gt; = 1.428, &lt;i&gt;p&lt;/i&gt; = 0.15) and food intake (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;2,40&lt;/sub&gt; = 0.904, &lt;i&gt;p&lt;/i&gt; = 0.43) remained unchanged among the experimental groups (Supporting Information S3). After 16 weeks of chemical exposure (Figure 1A), the B[&lt;i&gt;a&lt;/i&gt;]P, RET 10 μM and 30 μM groups developed papules, fungiform nodules and isolated leukoplastic plaques. In contrast, the SC and RET 10 μM groups exhibited skin thickening, wrinkling, minor ulcers and scaly hyperkeratosis, likely resulting from continuous acetone application. The InL varied significantly among groups (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;6,34&lt;/sub&gt; = 8.601, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) (Figure 1B)","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818630","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}

{"title":"Foetal Exposure to Phthalates and Endocrine Effects on the Leydig Cell","authors":"Sarah Philbert Nielsen,&nbsp;Line Mathiesen,&nbsp;Peter Møller","doi":"10.1111/bcpt.70035","DOIUrl":"https://doi.org/10.1111/bcpt.70035","url":null,"abstract":"<p>This review examines the association between early life exposure to phthalates in human males and Leydig cell endocrine function. A systematic search was performed in PubMed and EMBASE, identifying 17 studies for analysis. Association scores weighted for number of phthalates and subjects were calculated for luteinizing hormone (LH), testosterone, testosterone/LH ratio and insulin-like factor 3 (INSL3). The scores ranges from full consistency of positive (score = 1), through inconsistent (score = 0), to negative/inverse (score = −1) associations. LH and early life phthalate exposure showed a statistically significant weighted phthalate association score of 0.18. Testosterone showed largely null results, whereas testosterone/LH ratio showed a negative association, both not statistically significant. A rise in LH, and decrease of testosterone/LH ratio, indicates that early life phthalate exposure results in a demand for a larger LH stimulus to produce the same amount of testosterone, and perhaps a decreased function of the Leydig cells, that manifests with the onset of high testosterone production in puberty and adulthood. A statistically non-significant decrease in INSL3 with a weighted phthalate association score of −0.29 supports this finding. An early life phthalate exposure-induced decline in Leydig cell function could possibly impact the spermatogenesis and adult male fertility.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809729","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}