European journal of pharmacology最新文献

Corrigendum to “Rutaecarpine prevented ox-LDL-induced VSMCs dysfunction through inhibiting overexpression of connexin 43”[Eur J Pharmacol.853(2019) 84–92/EJP-49538] “Rutaecarpine通过抑制connexin 43的过度表达来预防ox- ldl诱导的VSMCs功能障碍”[J] .中国药理学杂志，2019,34(5):557 - 557。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-14 DOI: 10.1016/j.ejphar.2025.177694

Meiling Wang , Yusi Wu , Yanrong Yu , Yanqi Fu , Hang Yan , Xiaoying Wang , Tingting Li , Weijie Peng , Dan Luo

引用次数: 0

Inhibiting 5-HT_2C Receptor in the Hippocampus Rescues EphB2-Dependent Memory Impairment in Mice. 抑制海马5-HT2C受体对ephb2依赖性记忆损伤的修复作用

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-13 DOI: 10.1016/j.ejphar.2025.177729

Subhajit Jana, Sailendrakumar Kolatt Chandran, Kobi Rosenblum, Raphael Lamprecht

{"title":"Inhibiting 5-HT<sub>2C</sub> Receptor in the Hippocampus Rescues EphB2-Dependent Memory Impairment in Mice.","authors":"Subhajit Jana, Sailendrakumar Kolatt Chandran, Kobi Rosenblum, Raphael Lamprecht","doi":"10.1016/j.ejphar.2025.177729","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177729","url":null,"abstract":"<p><p>EphB2 is a tyrosine kinase receptor that regulates key neuronal functions such as synaptic transmission and morphogenesis. EphB2 dysfunction is associated with neurological disorders and dementia. In Alzheimer's disease, impaired EphB2 receptor function leads to memory deficits in mouse models, and its levels are reduced in patients. EphB2 expression also declines with aging. Moreover, EphB2 dysfunction has been linked to autism. Here, we show that long-term memory (LTM) of auditory fear conditioning is impaired in EphB2<sup>lacZ/lacZ</sup> male mice that lack EphB2 forward signaling. However, LTM was significantly increased when we microinjected the 5-HT<sub>2C</sub> serotonin receptor antagonist SB 242084 into the hippocampus before fear memory retrieval. SB 242084 microinjection before testing did not affect freezing in EphB2<sup>lacZ/lacZ</sup> when mice were exposed to the tone per se during training and testing. The 5-HT<sub>2C</sub> antagonist did not affect fear LTM in wild-type mice. SB 242084 was ineffective when injected before fear conditioning training. Microinjection of the 5-HT<sub>2C</sub> receptor agonist MK-212 into the hippocampus of wild-type mice before memory retrieval did not affect LTM. We further revealed that SB 242084 altered the intrinsic properties of pyramidal hippocampal neurons leading to increased excitability only in EphB2<sup>lacZ/lacZ</sup> but not in wild-type mice. The results show that memory is not lost in EphB2<sup>lacZ/lacZ</sup> mice but rather memory is inaccessible and can be recovered with 5-HT<sub>2C</sub> antagonists. Furthermore, it may be possible to rescue such memory impairments in brain diseases where EphB2 dysfunction is involved.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177729"},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Immune-endothelial cell crosstalk in hepatic endothelial injury of liver fibrotic mice 免疫内皮细胞串扰在肝纤维化小鼠肝内皮损伤中的作用。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-13 DOI: 10.1016/j.ejphar.2025.177730

Xue Fan , Qianhui Tang , Ninglin Xia , Jiwei Wang , Wen Zhao , Ming Jin , Qian Lu , Jinyu Hu , Rongmi Zhang , Luyong Zhang , Zhenzhou Jiang , Qinwei Yu

{"title":"Immune-endothelial cell crosstalk in hepatic endothelial injury of liver fibrotic mice","authors":"Xue Fan , Qianhui Tang , Ninglin Xia , Jiwei Wang , Wen Zhao , Ming Jin , Qian Lu , Jinyu Hu , Rongmi Zhang , Luyong Zhang , Zhenzhou Jiang , Qinwei Yu","doi":"10.1016/j.ejphar.2025.177730","DOIUrl":"10.1016/j.ejphar.2025.177730","url":null,"abstract":"<div><h3>Introduction</h3><div>Liver fibrosis is a common pathological process in chronic liver disease, reflecting the advanced stage of the disease. Liver endothelial cells (ECs), especially liver sinusoidal endothelial cells (LSECs), are recognized as critical modulators of liver homeostasis and play essential roles in the recruitment and function of liver immune cells. In this study, we aimed to explore the mechanism of hepatic EC injury and the potential regulatory pathways of intercellular communication in liver fibrosis.</div></div><div><h3>Methods</h3><div>In this study, C57BL/6 male mice were treated with CCl<sub>4</sub> for 6 weeks to establish a liver fibrosis model. Masson staining and immunohistochemistry were performed to assess the extent of liver fibrosis. Hepatic endothelial injury was detected by using scanning electron microscopy (SEM) and PCR technology. Single-cell RNA sequencing (scRNA-seq) was performed to analyze phenotypic changes in nonparenchymal cells and dissect intercellular crosstalk.</div></div><div><h3>Results</h3><div>A total of 24,534 cells were clustered into 10 main cell subsets. The LSEC fenestrae and surface receptor expression were reduced, and the expression of Cd34 was upregulated. Liver ECs exhibited dense cellular crosstalk with immune cells (macrophages, T and B cells). The analysis of intercellular signaling pathways revealed that immune cells targeted liver ECs through the Ptprc-Mrc1 and Sell-Podxl signaling pathways to maintain cellular interactions during liver fibrosis.</div></div><div><h3>Conclusion</h3><div>We revealed apparent damage and capillarization of liver ECs and demonstrated the cell-cell communications among liver immune cells and ECs during the development of liver fibrosis. The Ptprc-Mrc1 and Sell-Podxl signaling pathways exerted prominent roles in liver immune cell-EC interactions.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177730"},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Activation of the Nrf2 pathway by a novel bipyrazole compound mitigates doxorubicin-induced cardiotoxicity in Wistar albino rats 一种新型联吡唑化合物激活Nrf2通路可减轻阿霉素诱导的Wistar白化大鼠心脏毒性

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-13 DOI: 10.1016/j.ejphar.2025.177731

Abdelrahim Alqudah , Esam Qnais , Yousra Bseiso , Sireen Abdul Rahim Shilbayeh , Alaa A.A. Aljabali , Omar Gammoh

{"title":"Activation of the Nrf2 pathway by a novel bipyrazole compound mitigates doxorubicin-induced cardiotoxicity in Wistar albino rats","authors":"Abdelrahim Alqudah , Esam Qnais , Yousra Bseiso , Sireen Abdul Rahim Shilbayeh , Alaa A.A. Aljabali , Omar Gammoh","doi":"10.1016/j.ejphar.2025.177731","DOIUrl":"10.1016/j.ejphar.2025.177731","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX) clinical utility is limited by its dose-dependent cardiotoxicity. This study aimed to evaluate the cardioprotective potential of 2′,3,3,5′-Tetramethyl-4′-nitro-2′H-1,3′-bipyrazole (TMNB) in a rat model of DOX-induced cardiac injury.</div></div><div><h3>Methods</h3><div>Rats were divided into control, DOX, TMNB, and TMNB + DOX groups. TMNB was administered for 14 days. A single dose of DOX was given on day 7. Serum, oxidative stress, cytokines, apoptosis markers, and Nrf2 pathway gene expression were assessed. One-way ANOVA followed by Tukey's post-hoc test were used.</div></div><div><h3>Results</h3><div>TMNB pretreatment reduced CK-MB and LDH levels by 42.9 % and 50 %, respectively (Cohen's d > 6.4, <em>p</em> < 0.001). Histologically, TMNB significantly reduced myocardial damage (d = 6.63). MDA levels declined by 45.1 % in TMNB-treated rats (d = 7.18), while antioxidant enzymes SOD and CAT increased by 99.4 % and 74.1 %, respectively (<em>p</em> < 0.001). TMNB restored GSH and GPx-1 levels, reversing DOX-induced oxidative depletion (all d > 4.7). Pro-inflammatory cytokines TNF-α and IL-1β were reduced with TMNB pretreatment by over 40 % (d > 9.3, <em>p</em> < 0.001). Similarly, TMNB significantly downregulated NF-κB gene expression (d = 9.46). Caspase-3 and Bax were reduced by 44.9 % and 65.5 %, respectively (<em>p</em> < 0.001), while Bcl-2 expression was restored. TUNEL staining confirmed reduced apoptosis (d = 11.20). TMNB increased Nrf2, HO-1, and NQO1 expression (Nrf2 d = 8.21) while decreasing Keap1 (<em>p</em> < 0.0001).</div></div><div><h3>Conclusion</h3><div>TMNB significantly mitigates DOX-induced cardiotoxicity likely via Nrf2 pathway activation. These findings support TMNB's potential as a cardioprotective adjunct during chemotherapy, warranting further investigation in chronic and clinical models.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177731"},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Estradiol Replacement Enhances Sweet Taste Preference in Ovariectomized Rats: Interaction with Energy Intake Regulation. 雌二醇替代增强去卵巢大鼠的甜味偏好：与能量摄入调节的相互作用。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-11 DOI: 10.1016/j.ejphar.2025.177719

Natsumi Kosugi, Konomi Kanamori, Sayaka Kondo, Aoi Takahashi, Nanako Sakagawa, Mio Nishimaki, Keiko Morimoto, Akira Takamata

{"title":"Estradiol Replacement Enhances Sweet Taste Preference in Ovariectomized Rats: Interaction with Energy Intake Regulation.","authors":"Natsumi Kosugi, Konomi Kanamori, Sayaka Kondo, Aoi Takahashi, Nanako Sakagawa, Mio Nishimaki, Keiko Morimoto, Akira Takamata","doi":"10.1016/j.ejphar.2025.177719","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177719","url":null,"abstract":"<p><p>Estrogens exert anorectic and anti-obesity effects via homeostatic regulation. However, their role in hedonic ingestive behavior, particularly in sweet taste preference, remains unclear. We examined the effects of estradiol replacement on the intake of sweetened solutions, water, and total energy in ovariectomized rats with concurrent access to sweetened solutions, water, and a standard rodent chow. Compared with the non-replaced (E2(-)) group, the estradiol-replaced (E2(+)) group exhibited a higher intake of various sweetened solutions, including those containing non-caloric artificial sweeteners and natural sugars. Food intake was lower in the E2(+) group than in the E2(-) group. Total energy intake was lower in the E2(+) group than in the E2(-) group when rats consumed water, sucralose, and fructose, but not when rats consumed glucose or sucrose. To explore the involvement of μ-opioid receptors in the estrogen-induced enhancement of sucrose intake, we chronically infused naltrexone (NTX), a partial μ-opioid receptor antagonist. NTX attenuated sucrose intake in the E2(+) group but not in the E2(-) group. By contrast, NTX reduced food intake in the E2(-) group. Additionally, c-Fos expression in the nucleus accumbens shell was attenuated by NTX in the E2(+) group during the short-term sucrose preference test. These findings suggest that estrogen enhances sweet taste preference and that available palatable glucose or sucrose diminishes the estrogen-induced attenuation of homeostatic energy intake. Moreover, μ-opioid receptors possibly play a role in the estrogen-induced enhancement of hedonic sweet taste preference, while they are involved in the enhancement of homeostatic food/energy intake in the absence of estrogen.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177719"},"PeriodicalIF":4.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Menstrual Blood and Endometrial Mesenchymal Stem/Stromal Cells: A Frontier in Regenerative Medicine and Cancer Therapy. 经血与子宫内膜间充质干细胞/基质细胞：再生医学和癌症治疗的前沿。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-09 DOI: 10.1016/j.ejphar.2025.177726

Maryam Rahnama, Navid Ghasemzadeh, Zeinab Latifi, Fatemeh Kheradmand, Fariba Abbasi Koukia, Khan Sharun, Ali Golchin

{"title":"Menstrual Blood and Endometrial Mesenchymal Stem/Stromal Cells: A Frontier in Regenerative Medicine and Cancer Therapy.","authors":"Maryam Rahnama, Navid Ghasemzadeh, Zeinab Latifi, Fatemeh Kheradmand, Fariba Abbasi Koukia, Khan Sharun, Ali Golchin","doi":"10.1016/j.ejphar.2025.177726","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177726","url":null,"abstract":"<p><p>The acquisition of suitable stem cell sources is a significant issue in regenerative medicine. There has been considerable interest in utilizing mesenchymal stem cells (MSCs) derived from endometrial and menstrual blood as a promising resource of MSCs, owing to their unique biochemical properties and prospective use in clinical therapies. This population of stem cells has distinct characteristics in terms of immunophenotype, proliferation rate, and differentiation capacity. A notable characteristic of these stem cells is their capacity to develop into mesodermal lineages, highlighting their regenerative capability. Moreover, the presence of certain surface markers facilitates the augmentation of clonogenic endometrial MSCs. Their distinctive characteristics, along with their swift multiplication ability, underscore their significant promise for therapeutic applicability in regenerative medicine and cell-based treatments. Current investigations are examining possible usage of diverse stem cell resources in the treatment of inflammatory diseases and perhaps intractable illnesses like Parkinson's disease, utilizing their immunomodulatory properties. This review aims to analyze stem cell-related research that has utilized endometrial and menstrual blood-derived MSCs (enMSCs and MenSCs) with a special focus on their clinical application. We will explore the existing evidence about the therapeutic potential for these stem cells across many medical diseases and address the obstacles and prospective trajectories in this domain. Additionally, we will study the unique properties of enMSCs and MenSCs that make them promising candidates for regenerative medicine.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177726"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Single-cell omics: moving towards a new era in ischemic stroke research 单细胞组学：迈向缺血性脑卒中研究的新时代

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-09 DOI: 10.1016/j.ejphar.2025.177725

Jieqiong Zeng , Huifen Zhou , Haitong Wan , Jiehong Yang

{"title":"Single-cell omics: moving towards a new era in ischemic stroke research","authors":"Jieqiong Zeng , Huifen Zhou , Haitong Wan , Jiehong Yang","doi":"10.1016/j.ejphar.2025.177725","DOIUrl":"10.1016/j.ejphar.2025.177725","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a highly complex and heterogeneous disease involving multiple pathophysiological events. A better understanding of the pathophysiology of IS will enhance preventive, diagnostic and therapeutic strategies. Despite significant advances in modern medicine, the molecular mechanisms of IS are still largely unknown. The high-throughput omics approach opens new avenues for identifying IS biomarkers and elucidating disease pathogenesis mechanisms. Single-cell omics enables a more thorough and in-depth analysis of the cellular interactions and properties in IS. This will lead to a better understanding of the onset, treatment and prognosis of IS. In this paper, we first reviewed the disease signatures and mechanisms research of IS. Subsequently, the use of single-cell omics to comprehend the mechanisms of IS was discussed, along with some recent developments in the field. To further delineate the upstream pathogenic alterations and downstream molecular impacts of IS, we also discussed the current use of machine learning approaches to single-cell omics data analysis. Particularly, single-cell omics is being used to inform risk assessment, early patient diagnosis and treatment strategies, and their potential impact on precision medicine. Thus, we summarized the role of single-cell omics in precision medicine. Despite the relative youth of the field, the development of single-cell omics promises to provide a powerful tool for elucidating the pathogenesis of IS.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177725"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

In Vivo and In Vitro Crosstalk Among CBD, Aβ, and Endocannabinoid System Enzymes and Receptors. CBD， Aβ和内源性大麻素系统酶和受体的体内外串扰。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-09 DOI: 10.1016/j.ejphar.2025.177720

Fangyuan Duan, Dan Xiao, Jiayu Wang, Runze Li, Xiaoyue Si, Weihong Lu

{"title":"In Vivo and In Vitro Crosstalk Among CBD, Aβ, and Endocannabinoid System Enzymes and Receptors.","authors":"Fangyuan Duan, Dan Xiao, Jiayu Wang, Runze Li, Xiaoyue Si, Weihong Lu","doi":"10.1016/j.ejphar.2025.177720","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177720","url":null,"abstract":"<p><p>Cannabidiol (CBD), a non-psychotropic compound derived from Cannabis sativa, has garnered attention as a potential therapeutic agent for various neurodegenerative diseases, including Alzheimer's disease (AD). Despite growing interest, additional research is required to clarify the specific mechanisms by which CBD influences the pathological accumulation of β-amyloid (Aβ) associated with AD. Moreover, the interactions between CBD and the endocannabinoid system (ECS), both in the presence and absence of Aβ expression, remain a subject of active investigation. Elucidating these mechanisms may provide valuable insights for advancing both our understanding and the development of targeted interventions in neurodegenerative disease management. Using a multifaceted approach that integrates pharmacological interventions, immunofluorescence imaging, flow cytometry, and biochemical assays, we examined the effects of CBD on Aβ40 and Aβ42. Additionally, we analyzed the modulation of cannabinoid receptor 1(CB1 receptor) and fatty acid amide hydrolase (FAAH) in the presence or absence of Aβ expression, uncovering the intricate regulatory mechanisms of CBD. Our findings indicate a nuanced response to CBD; while it may produce side effects in non-pathological cells, it demonstrates an ability to induce autophagy and apoptosis in Aβ-expressing cells via the activation of the Microtubule-associated protein 1 light chain 3 B(LC3B) and Caspase-3 pathways. Furthermore, our investigation into faah-1 involvement highlighted its role in alleviating pharyngeal dysfunction and counteracting weight loss in Aβ-expressing Caenorhabditis elegans(C. elegans) strains. These insights advance our understanding of CBD's therapeutic potential in addressing neurodegenerative pathologies.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177720"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Eating a high fat/high carbohydrate diet enhances morphine tolerance, while eating a ketogenic diet mitigates morphine withdrawal in male rats 吃高脂肪/高碳水化合物的饮食可以增强吗啡耐受性，而吃生酮饮食可以减轻雄性大鼠的吗啡戒断。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-08 DOI: 10.1016/j.ejphar.2025.177709

Nina M. Beltran , Leslie L. Sullivan , Gabriela M. Naime , Vanessa Minervini , Katherine M. Serafine

{"title":"Eating a high fat/high carbohydrate diet enhances morphine tolerance, while eating a ketogenic diet mitigates morphine withdrawal in male rats","authors":"Nina M. Beltran , Leslie L. Sullivan , Gabriela M. Naime , Vanessa Minervini , Katherine M. Serafine","doi":"10.1016/j.ejphar.2025.177709","DOIUrl":"10.1016/j.ejphar.2025.177709","url":null,"abstract":"<div><div>Obesity is associated with greater prescription rates of pain-relieving drugs (i.e., opioids). However, it is not known if opioid sensitivity is altered by diet, in particular with regard to fat and carbohydrate consumption. While eating a high fat/high carbohydrate diet leads to weight gain, a high fat/low carbohydrate diet (i.e., a ketogenic diet) leads to weight loss. In this report, male Sprague-Dawley rats (<em>n</em> = 7–8/dietary group) ate either a standard, high fat/high carbohydrate, or ketogenic diet. Morphine-induced antinociception was evaluated using the warm water tail withdrawal procedure following saline or cumulative doses of morphine (0.32–56 mg/kg; i.p.). After acute morphine testing, rats were administered morphine twice-daily, increasing in quarter log doses every 3 days (3.2–56 mg/kg; i.p) for 19 days to induce dependence and evaluate tolerance. Next, naltrexone-precipitated withdrawal was evaluated. Based on previous data, it was hypothesized that the magnitude of tolerance would be greater from eating a high fat/high carbohydrate diet, while withdrawal would be less severe for rats eating a ketogenic diet. Antinociception induced by acute doses of morphine was comparable among groups, regardless of diet. Further, rats in all groups developed tolerance to morphine; however, the magnitude of tolerance was greater for rats eating the high fat/high carbohydrate diet as compared to those eating a ketogenic diet. Rats eating a ketogenic diet displayed less severe withdrawal than rats in other groups. These results suggest that dietary intake can impact morphine sensitivity in ways that might be relevant for chronic pain management and opioid use disorder.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177709"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Delirium risk associated with esketamine, sevoflurane, propofol, and dexmedetomidine: A real-world study based on the FDA adverse event reporting system 谵妄风险与艾氯胺酮、七氟醚、异丙酚和右美托咪定相关：基于FDA不良事件报告系统的真实世界研究

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-05-08 DOI: 10.1016/j.ejphar.2025.177723

Yichun Shuai, Yan Liu, Xiahong Yang, Qiaoqian Wan, Jie Zhao, Xin Wang

{"title":"Delirium risk associated with esketamine, sevoflurane, propofol, and dexmedetomidine: A real-world study based on the FDA adverse event reporting system","authors":"Yichun Shuai, Yan Liu, Xiahong Yang, Qiaoqian Wan, Jie Zhao, Xin Wang","doi":"10.1016/j.ejphar.2025.177723","DOIUrl":"10.1016/j.ejphar.2025.177723","url":null,"abstract":"<div><h3>Objective</h3><div>Delirium is a serious postoperative complication, increasingly recognized for its heightened risk following the use of sedative drugs. This study aimed to assess the relationship of esketamine, sevoflurane, propofol, and dexmedetomidine with the risk of delirium.</div></div><div><h3>Methods</h3><div>Data were obtained from the FDA Adverse Event Reporting System (FAERS) database covering the period from the first quarter of 2004 to the second quarter of 2024. Cases of delirium associated with these medications were identified using preferred terms (PTs) defined by the Medical Dictionary for Regulatory Activities (MedDRA 20.0). Disproportionality analyses employed reported odds ratios (ROR) and multiple gamma-Poisson shrinkage (MGPS), while logistic regression assessed the effects of age and sex on the risk of delirium.</div></div><div><h3>Results</h3><div>A total of 21,433,114 adverse events (AEs) were recorded in the FAERS database, including 16 cases of delirium associated with esketamine, 189 with propofol, 90 with sevoflurane, and 103 with dexmedetomidine. Propofol (ROR: 5.44, EBGM05: 4.8), sevoflurane (ROR: 9.9, EBGM05: 8.26), and dexmedetomidine (ROR: 21.1, EBGM05: 17.67) were significantly associated with the delirium risk, whereas esketamine (ROR: 1.45, EBGM05: 0.96) did not show a significant association. Age was identified as a significant risk factor for delirium, particularly in patients aged 55 years and older.</div></div><div><h3>Conclusion</h3><div>The findings indicate a significant correlation between propofol, sevoflurane, and dexmedetomidine and the risk of delirium, whereas esketamine does not appear to have a significant association with delirium. Future studies should further explore drug administration and dosage effects on delirium risk to improve clinical safety.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177723"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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