Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Correction to ‘Initiation of Anticoagulants During the COVID-19 Pandemic in Sweden: An Interrupted Time Series Analysis’","authors":"","doi":"10.1111/bcpt.70055","DOIUrl":"https://doi.org/10.1111/bcpt.70055","url":null,"abstract":"<p>\u0000 <span>P.-J. Samuelsen</span>, <span>B. Wettermark</span>, <span>F. Nyberg</span>, <span>M. Hajiebrahimi</span>, “ <span>Initiation of Anticoagulants During the COVID-19 Pandemic in Sweden: An Interrupted Time Series Analysis</span>,” <i>Basic &amp; Clinical Pharmacology &amp; Toxicology</i> <span>136</span>, no. <span>2</span> (<span>2025</span>): e14119, https://doi.org/10.1111/bcpt.14119.\u0000 </p><p>In the article cited above, several discrepancies occurred between the final author-approved manuscript and the published version.</p><p>\u0000 <b>Confidence intervals</b>\u0000 </p><p>\u0000 <b>In-text citation corrections</b>\u0000 </p><p>\u0000 <b>Reference list corrections</b>\u0000 </p><p>Reference [32] cited a corrigendum instead of the original guideline. The correct reference is:</p><p>G. Hindricks, T. Potpara, N. Dagres, et al., “2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC,” <i>European Heart Journal</i> 42, no. 5 (2021): 373–498, https://doi.org/10.1093/eurheartj/ehaa612.</p><p>In addition, seven references contained minor inaccuracies. The corrected references are listed in the table below:\u0000 </p><p>These corrections do not affect the conclusions of the article. We apologize for this error.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944591","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":"Rutin-Associated Hepatoprotection: A Review of Mechanisms and Therapeutic Prospects","authors":"Yanting Feng,&nbsp;Lanchun Peng,&nbsp;Xiaohui Liu,&nbsp;Qingzhu Zheng,&nbsp;Min Qian,&nbsp;Meiling Deng,&nbsp;Jiangli Peng,&nbsp;Yamei Li,&nbsp;Limei Lin,&nbsp;Qiuxian Peng","doi":"10.1111/bcpt.70042","DOIUrl":"https://doi.org/10.1111/bcpt.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Liver disorders pose a considerable global health challenge, accompanied by rising mortality rates. Current therapeutic strategies, though effective, often face limitations due to adverse effects and therapeutic resistance, prompting the exploration of alternative treatments, particularly safer natural compounds. Rutin, a widely available bioflavonoid, has emerged as a promising candidate owing to its varied pharmacological properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive search on PubMed and Web of Science using the following keywords: ‘rutin’, ‘liver diseases’, ‘hepatoprotection’, ‘clinical observations’, ‘mechanisms, pharmacology’ and various combinations of these terms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review systematically examines rutin's therapeutic potential in hepatic disorders, focusing on its molecular mechanisms, particularly its effects on inflammatory pathways, oxidative stress and hepatocellular protection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We analyse existing evidence supporting rutin's hepatoprotective efficacy, identify its cellular and molecular targets and evaluate its potential applications in various liver diseases. Our systematic analysis provides theoretical support for developing rutin-based therapies in hepatic disease management and identifies future research directions and clinical applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939546","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":"Differences in the Inflammatory Response and Corticoid Responsiveness of Human Lung Macrophages and Parenchymal Explants Exposed to Cigarette Smoke Extracts","authors":"Marion Brollo,&nbsp;Quentin Marquant,&nbsp;Hélène Salvator,&nbsp;Justine Cohen,&nbsp;Matthieu Glorion,&nbsp;Alexis Ferré,&nbsp;Martin Dres,&nbsp;Nicolas Roche,&nbsp;Stanislas Grassin-Delyle,&nbsp;Philippe Devillier","doi":"10.1111/bcpt.70046","DOIUrl":"https://doi.org/10.1111/bcpt.70046","url":null,"abstract":"<p>Smoking is the main cause of chronic obstructive pulmonary disease (COPD) and is associated with corticosteroid resistance. Given the paucity of data on human lung preparations, macrophages (LMs), and parenchymal explants (LPEs) were exposed to cigarette smoke extracts (CSE) in the presence or absence of lipopolysaccharide (LPS). Moreover, LMs and LPEs were treated with budesonide prior exposure to CSE or LPS. The levels of cytokines (TNF-α, IL-6) and chemokines (CCL2, CCL4, CXCL1, CXCL5, and CXCL8) in the supernatants were measured using ELISAs.</p><p>In LMs, exposure to CSE was not associated with significant difference in the production of cytokines and chemokines, with the notable exception of greater CXCL8 production. The results were generally the same for LPEs. CSE exposure did not potentiate the LPS-induced production of the cytokines and chemokines and even tended to reduce this production in LMs and LPEs. Lastly, CSE exposure inhibited budesonide’s anti-inflammatory activity in LMs but not in LPEs.</p><p>This study extends the data on the CSE inflammatory effects and its inhibition of corticosteroid efficacy in human lung preparations. Our findings question the relevance of these preparations with regard to the long-term toxicity of smoking and the corticosteroid resistance observed in smokers and in patients with COPD.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925898","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":"The Potential Ability of Betulinic Acid to Prevent Experimentally Induced Acute Pancreatitis in Rats","authors":"Guler Yenice,&nbsp;Seckin Ozkanlar,&nbsp;Ismail Bolat,&nbsp;Serkan Yildirim","doi":"10.1111/bcpt.70052","DOIUrl":"https://doi.org/10.1111/bcpt.70052","url":null,"abstract":"<p>Acute pancreatitis (AP) is a serious pancreatic inflammatory disease that results in pancreatic enzyme activation and autodegradation. Betulinic acid (BA), a pentacyclic triterpene of natural origin that was isolated from several plants, has anti-inflammatory, immunomodulatory and antioxidant effects that can help with AP. With this study, we aimed to investigate the potential positive effects of BA on <span>l</span>-arginine-induced AP. A total of 24 male rats were divided into four groups (control, BA, AP and BA + AP). Animals in the BA group were given BA 50 mg/kg/day for 7 days. AP was induced by administering two doses of 250-mg/100-g <span>l</span>-arginine to animals in the AP group. The animals in the BA + AP group were administered 50-mg/kg/day BA (gavage) for 7 days and two doses of 250-mg/100-g <span>l</span>-arginine on the seventh day. BA pretreatment inhibited the increased lipase activity caused by AP and showed protective activity against oxidative damage to pancreatic tissue. It decreased the severity of inflammation by suppressing the release of pro-inflammatory cytokines while increasing the level of the anti-inflammatory cytokine IL-10. It showed a protective effect on pancreatic tissue by inhibiting tumour necrosis factor (TNF-α) and Bax expression. The findings of the study show that BA exhibits multifaceted protective activity in experimental AP induced with <span>l</span>-arginine.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925899","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":"Emergency Department Visits due to Medication Overdose in a Finnish University Hospital","authors":"Sami Mustajoki,&nbsp;Aleksi Reito,&nbsp;Kalle Peltonen","doi":"10.1111/bcpt.70053","DOIUrl":"https://doi.org/10.1111/bcpt.70053","url":null,"abstract":"<p>There are no recent reports from the Nordic countries describing emergency department (ED) visits due to medication overdose.</p><p>All patients visiting EDs of Tampere University Hospital, Finland, with ICD-10 codes T36–T50.9 during the year of 2021 were included in this study.</p><p>A total of 803 ED visits by 631 individual patients were identified, comprising 0.7% of all ED visits in 2021. The intention of the overdose was self-harm in 70%, inebriation in 17% and other in 13% of the visits. The mean age of the patients was 35 (range 1–95) years, and 63% were female. In 52% of the visits, the patient had taken more than one medication. Benzodiazepines were involved in 40% of the visits, followed by antipsychotics (28%), antidepressants (19%), paracetamol (15%) and opiates (13%). Twenty-six percent of the patients were admitted to the intensive care or high-dependency care unit, but there were no overdose-related in-hospital deaths. The overall 1-year mortality rate after an overdose was 2.8%.</p><p>The intention of a medication overdose was most often self-harm, followed by inebriation. Over half of the overdoses were multidrug overdoses, and psychoactive medications were predominantly used. There were no in-hospital deaths related to medication overdoses.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909450","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":"Poisonings With Opioids and Benzodiazepines in Denmark: A Retrospective Study From the Danish Poison Information Centre","authors":"Alba K. V. Sigfredsson,&nbsp;Dorte Fris Palmqvist,&nbsp;Kim Dalhoff","doi":"10.1111/bcpt.70044","DOIUrl":"https://doi.org/10.1111/bcpt.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This study describes opioid and benzodiazepine poisonings in Denmark from 2014 to 2022. The analgesic effect of opioids and sedative effect of benzodiazepines are used to treat pain, insomnia and anxiety disorders and can cause abuse and addiction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A retrospective observational register study with data from the Danish Poison Information Centre with alprazolam, clonazepam, oxazepam, buprenorphine, diacetylmorphine, methadone, morphine, oxycodone and tramadol poisonings. Multiple recordings of the same exposure are only registered once.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Totally 10 965 enquiries were included with a 55/43% female/male ratio (2% unaccounted). The number of enquiries regarding poisonings with alprazolam increased from 56 in 2014 to 289 in 2022 (+416%) or from 2.27 to 7.71 per 1000 enquiries to the DPIC (+240%). The corresponding numbers regarding the other eight substances were buprenorphine [22/33 (+50%); 0.89/0.88 (−1%)], morphine [125/250 (+100%); 5.06/6.67 (+32%)], oxazepam [240/364 (+52%); 9.71/9.71 (0%)], oxycodone [44/199 (+352%); 1.78/5.31 (+198%)], tramadol [262/421 (+61%); 10.6/11.23 (+6%)], methadone [65/63 (−3%); 2.63/1.68 (−36%)], clonazepam [60/92 (+53%); 2.43/2.45 (+1%)] and diacetylmorphine [17/20 (+18%); 0.69/0.53 (−23%)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In our 9-year study period, we observed large increases in poisonings with alprazolam and oxycodone. In the remaining drugs examined, we observed no change or even a reduction of the poisonings when adjusted for the general increase in enquiries to the DPIC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909353","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":"Preparing the Future of Research on Deprescribing: Results From a Survey of Early Career Researchers at the 2nd International Conference on Deprescribing","authors":"Jérôme Nguyen-Soenen,&nbsp;Thomas Morel,&nbsp;Kristie Rebecca Weir","doi":"10.1111/bcpt.70049","DOIUrl":"https://doi.org/10.1111/bcpt.70049","url":null,"abstract":"&lt;p&gt;Deprescribing is an expanding area of research with the term first coined in the scientific literature by Woodward in 2003 [&lt;span&gt;1&lt;/span&gt;] and was defined by consensus by Reeve et al. in 2015 [&lt;span&gt;2&lt;/span&gt;]. Consequently, the growing community of deprescribing researchers has led to an increasing number of students and a rise in early career researchers (ECRs) in the field.&lt;/p&gt;&lt;p&gt;An ECR is generally defined as someone within the first 5 years of academic or research-related employment following the completion of their postgraduate training, with a focus on stable research development [&lt;span&gt;3&lt;/span&gt;]. ECRs often face challenges, including securing funding and research grants, balancing the pressure to publish with clinical, teaching or administrative duties, limited job security, and transitioning from supervised to independent research. They can also face difficulties in establishing collaborations, building a professional network, and gaining recognition in their field [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Conferences are an avenue for collaboration, networking and reputation-building in academic communities. The first International Conference on Deprescribing (ICOD) was held in Kolding, Denmark in 2022 followed by ICOD2 in Nantes, France, in 2024. These events brought together global stakeholders, researchers, clinicians and healthcare professionals focused on deprescribing. Our research investigated ECRs' experiences within this community. Our purpose was to characterize the ECRs, the challenges they face, and their insights on the development of a group to support them.&lt;/p&gt;&lt;p&gt;We defined ECR as ‘students or within 5 years of obtaining their PhD or highest degree, not including breaks for part-time work, parental leave, clinical training or health reasons’. Participants of ICOD2 were asked to identify as an ECR when they registered. We distributed an online survey via email on 20 September 2024, with participants having until the start of the conference on 24 September 2024, to submit their responses. Preliminary survey results were presented at an ICOD2 ECR seminar and networking event at the conference.&lt;/p&gt;&lt;p&gt;LimeSurvey (LimeSurvey GmbH, 2023) was used to create the questionnaire. The survey contained 13 questions on demographics, research focus, conference participation, future directions and feedback (Data S1). Future directions included questions on career aspirations, challenges faced and the possible formation of an ECR group. The feedback questions focused on topics of interest at the conference and how the conference could provide support for ECR. The questions were designed by the authors in collaboration with two experts in deprescribing research. The responses were multiple choice, free text or ‘Yes/No’. Responses were anonymous and confidential, and participation was voluntary.&lt;/p&gt;&lt;p&gt;A descriptive analysis was conducted using Excel (Microsoft Corporation, 2021). We defined participants who had a healthcare profession as ‘clinician researc","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908956","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":"Billing Deprescribing Interventions: Portrait of an Initiative in Québec, Canada","authors":"Alexandre Campeau Calfat,&nbsp;Maude Gosselin,&nbsp;Caroline Sirois","doi":"10.1111/bcpt.70050","DOIUrl":"https://doi.org/10.1111/bcpt.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Deprescribing is a patient-centred process in which a healthcare professional reduces or stops medications to improve health outcomes. Since late 2022, community pharmacists in Québec, Canada, have been able to bill for deprescribing interventions, enabling more robust deprescribing research in large cohort studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to assess the prevalence of deprescribing claims in Québec community pharmacies from January 1, 2023, to November 30, 2024, and to identify the most commonly deprescribed medication classes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed the total number of deprescribing claims submitted by pharmacists during this period and categorized deprescribed medications using the American Hospital Formulary Service classification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Over 90 000 claims were submitted for deprescribing interventions, with most involving central nervous system medications. Although the number of claims increased over time, the overall volume remained modest.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While limitations remain, such as the gradual adoption of billing interventions, Québec's reimbursement model for deprescribing interventions provides an important framework for research, offering a mechanism to study deprescribing in real-world settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897040","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":"Acetaminophen in Pregnancy: A Population-Level Drug-Utilization Study of Prescription-Based Acetaminophen Use Among Pregnant Women in Denmark From 2001 to 2023","authors":"S. Pflugfelder,&nbsp;E. B. Gram,&nbsp;P. Damkier","doi":"10.1111/bcpt.70048","DOIUrl":"https://doi.org/10.1111/bcpt.70048","url":null,"abstract":"<p>Acetaminophen is the most used analgetic drug for pain management during pregnancy. A recent academic controversy concerns the safety of acetaminophen during pregnancy related to a potentially increased risk of adverse neurodevelopmental effects. We investigated the population-level trends in prescription-based use of acetaminophen among pregnant women in Denmark between 2001 and 2023. Prescription-based sals of acetaminophen among pregnant women and comparison groups were retrieved from ‘eSundhed’, a publicly available dataset curated by the Danish Health Authorities. The number of prescription-based drug users per 1000 pregnant women increased slightly from 2001 to 2012 (3.9 to 6.5 per 1000) and 2015 to 2023 (52 to 76 per 1000), interrupted by a drastic increase in 2013/2014. Acetaminophen use among pregnant women (2023: 76 per 1000) was lower than in women in an age-matched comparison group (137 per 1000) and in women 12–3 months prior to pregnancy (124 per 1000). Time trends did not notably differ between age groups or comparison groups. Prescription-based acetaminophen sales among pregnant women increased by 50% from 2015 to 2023. A general shift in the prescription pattern towards a substantial increase in prescription-based exposure was observed following legislation changes in 2013, restricting sales of large packages to prescription.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896950","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":"The Synthetic LXR Agonist GW3965 Attenuates Phosgene-Induced Acute Lung Injury Through the Modulation of PI3K/Akt and NF-κB Signalling Pathways","authors":"Dong Yan,&nbsp;Yuanwei Fu,&nbsp;Jie Mei,&nbsp;Junhong Wang,&nbsp;Ayijiang Jiamaliding,&nbsp;Ying Liu,&nbsp;Zanmei Zhao,&nbsp;Qingbian Ma","doi":"10.1111/bcpt.70045","DOIUrl":"https://doi.org/10.1111/bcpt.70045","url":null,"abstract":"<p>Phosgene, used in large-scale industrial production, is highly toxic and irritant. Accidental exposure can lead to varying degrees of injuries, with severe cases potentially resulting in acute lung injury or acute respiratory distress syndrome, resulting in a mortality rate of 40%–50%. The indirect damages of phosgene (inflammation and oxidative stress) are considered important factors in phosgene-induced acute lung injury (P-ALI). The expression of Liver X Receptor α (LXRα) significantly reduces during periods of inflammation. LXRs were initially discovered to be highly expressed in the liver, whereas LXRs are expressed in immune cells and vascular endothelial cells, playing a significant role in anti-inflammatory and antioxidant responses. LXRα may have pulmonary protection in P-ALI. However, evidence to verify this association is still lacking. In this study, rats were divided into six groups to explore the potential role of LXRα in P-ALI. This study found that GW3965 effectively activated LXRα, upregulated its expression and downregulated the levels of proinflammatory cytokines, inhibited malondialdehyde activity while enhancing superoxide dismutase activity, suppressed apoptosis and ameliorated the pathological processes of P-ALI, ultimately exerting pulmonary protection in P-ALI. Further validation revealed that the pulmonary protective effect of LXRα may be associated with the PI3K/Akt and NF-kB signalling pathways.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896949","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}