Basic & Clinical Pharmacology & Toxicology最新文献

{"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}

{"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}