European journal of pharmacology最新文献

{"title":"Corrigendum to \"Effects of maternal smoking on inflammation, autophagy/mitophagy, and miRNAs in endothelial cells: Influence of newborn sex\" [Europ. J. Pharmacol. 998 (2025) 177648].","authors":"Flavia Franconi, Valeria Lodde, Giampiero Capobianco, Massimo Criscione, Andrea Montella, Ilaria Campesi","doi":"10.1016/j.ejphar.2025.177930","DOIUrl":"10.1016/j.ejphar.2025.177930","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177930"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616895","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}

{"title":"Corrigendum to: \"Involvement of protein A and IL-16 in the hyperalgesia and allodynia evoked by Staphylococcus aureus in mice\" [Eur J Pharmacol. 2025 1002:177861].","authors":"Luis Menéndez, Alejandro Álvarez-Artime, Sara González-Rodríguez, Gemma Fernández-García, María González-Amor, Ángel Manteca, Ana Baamonde","doi":"10.1016/j.ejphar.2025.177876","DOIUrl":"10.1016/j.ejphar.2025.177876","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177876"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564710","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}

{"title":"Corrigendum to \"Combination therapy with citalopram, bupropion, and lithium for the amelioration of the depressive-related effects induced by dexamethasone in male mice\" [Eur. J. Pharmacol. 1002 (2025) 177780].","authors":"Elmira Daliri, Zahra Hamyani, Ali Arjangi, Fatemeh Khakpai, Sakineh Alijanpour, Mohammad-Reza Zarrindast","doi":"10.1016/j.ejphar.2025.177835","DOIUrl":"10.1016/j.ejphar.2025.177835","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177835"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599836","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}

{"title":"Corrigendum to \"Dietary alpha-lipoic acid prevents depression-like and anxiety-like behavior under aircraft noise exposure in young adult male mice\" [Eur. J. Pharmacol. 1002 (2025) 177834].","authors":"Kangli Zhang, Liyong Yan, Xiaojing Lin, Chenyi Li, Xueqing Yi, Zhongya Shi, Cheng-Hsien Lin, Gang Sun","doi":"10.1016/j.ejphar.2025.177904","DOIUrl":"10.1016/j.ejphar.2025.177904","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177904"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607789","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}

{"title":"Dipyrone induces sex-dependent latent sensitization in a preclinical model of medication overuse headache","authors":"Fernanddo José Spagnol ,&nbsp;Julia Maria Zortea ,&nbsp;Larissa Cieslinsky Gomes ,&nbsp;Fernanda Mariano Ribeiro da Luz ,&nbsp;Darciane Favero Baggio ,&nbsp;Vanessa Bordenowsky Pereira Lejeune ,&nbsp;Luiz Eduardo Nunes Ferreira ,&nbsp;Caroline Machado Kopruszinski ,&nbsp;Juliana Geremias Chichorro","doi":"10.1016/j.ejphar.2025.178173","DOIUrl":"10.1016/j.ejphar.2025.178173","url":null,"abstract":"<div><div>The excessive use of medications for the symptomatic treatment of primary headaches can lead to the development of Medication Overuse Headache (MOH), a secondary chronic headache. It is considered that the excessive use of any over-the counter analgesic can induce MOH, but there is little preclinical and clinical evidence. This study aimed to evaluate whether prolonged exposure to dipyrone (metamizole) in both male and female rats induces MOH. First, the acute effect of dipyrone (60 mg/kg) was assessed in migraine-related responses induced by injection of calcitonin-gene related peptide (CGRP, 0.1 nmol/10 μL) in the trigeminal ganglion. Next, the animals were orally treated with dipyrone (120 mg/kg, 2 x day/30 days) and the periorbital mechanical threshold was assessed at 5-day intervals. At the end of the treatment, the animals were exposed to a bright light for allodynia reinstatement. Mechanical thresholds in the hindpaw region, locomotor activity as well as plasma levels of CGRP were also assessed. A single administration of dipyrone reduced periorbital mechanical allodynia induced by CGRP in male and female rats. Male and female rats treated with dipyrone for 30 days did not show any change in the periorbital mechanical threshold. However, chronic dipyrone induced latent sensitization, revealed by bright light exposure, selectively in females. Prolonged dipyrone treatment did not affect the paw mechanical threshold, the locomotory behavior, or the plasmatic levels of CGRP. These results suggest that prolonged treatment with dipyrone can cause sensitization of the trigeminal system and potentially induced MOH, with females being more vulnerable.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178173"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079999","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}

{"title":"Selective PI3Kγ inhibition attenuates chemotherapy-induced intestinal mucositis without compromising the anticancer properties of irinotecan","authors":"Aurilene Gomes Cajado ,&nbsp;Marina Helena Lopes ,&nbsp;Gisele Fátima Pinheiro Rangel ,&nbsp;Kayanny Queiroz Ferreira ,&nbsp;Celia Choquenaira Quispe ,&nbsp;Raiza Lima Silva ,&nbsp;Luana Maria Moura Ferreira ,&nbsp;Lívia Maria Soares Nobre ,&nbsp;Jussara Matyelle Rodrigues Silva ,&nbsp;Lízias Claudia Sampaio Quintela ,&nbsp;Ana Lizeth Padilha Paguada ,&nbsp;Anamaria Falcão Pereira ,&nbsp;Ana Paula Negreiros Nunes Alves ,&nbsp;Nylane Maria Nunes Alencar ,&nbsp;Roberto César Pereira Lima-Júnior ,&nbsp;Deysi Viviana Tenazoa Wong","doi":"10.1016/j.ejphar.2025.178165","DOIUrl":"10.1016/j.ejphar.2025.178165","url":null,"abstract":"<div><div>Irinotecan-based anticancer therapy induces intestinal mucositis, increasing the risk of sepsis and patient death. The phosphoinositide 3-kinases (PI3K) are involved in cancer and inflammatory diseases, but their role in intestinal mucositis remains unknown. C57BL/6 male mice received vehicle (1 % DMSO, 10 ml/kg, p.o.), irinotecan alone or in combination with AS-605240 (a PI3Kγ inhibitor, 10 mg/kg, p.o.) or GSK2269557 (a PI3Kδ inhibitor, 3 mg/kg, p.o.). Histopathology, inflammatory markers, and diarrhea were assessed to evaluate mucositis. The antitumor effect was evaluated in mice inoculated with the Mc-38 colorectal cancer cell line. PI3Kγ inhibition attenuated irinotecan-induced intestinal injury, as evidenced by improved villus/crypt ratio. PI3Kγ inhibition also caused milder neutrophil accumulation, reduced expression of <em>Tlr2</em>, <em>Tlr4</em>, and <em>Tlr9</em>, and decreased levels of interleukin-1β and −6, as well as attenuated immunofluorescence for F4/80, a macrophage marker, and the regulatory T cell transcription factor FOXP3 (P &lt; 0.05 <em>vs.</em> irinotecan). Additionally, AS-605240 prevented goblet cell loss and attenuated diarrhea. Moreover, PI3Kγ inhibition combined with irinotecan showed no synergistic anticancer effects. In contrast, PI3Kδ blockade did not prevent the development of mucositis but rather enhanced neutrophil accumulation in the intestine. PI3Kγ inhibition attenuates chemotherapy-associated intestinal mucositis without compromising the anticancer efficacy of irinotecan. However, selective inhibition of PI3Kδ exacerbates the inflammatory response and tissue damage.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178165"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080053","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}

{"title":"Prognostic implications of antitumour efficacy and adverse events of EGFR-TKIs in non-small cell lung cancer: an ambispective cohort study","authors":"Ling Yong ,&nbsp;Yan'e Liu ,&nbsp;Weizhe Jian ,&nbsp;Lei Cai ,&nbsp;Tianyu Bao ,&nbsp;Pingyao Luo ,&nbsp;Enze Gan ,&nbsp;Chen Liu ,&nbsp;Tianyu Wang ,&nbsp;Qingyu Yao ,&nbsp;Rong Chen ,&nbsp;Baoshan Cao ,&nbsp;Wei Liu ,&nbsp;Tianyan Zhou","doi":"10.1016/j.ejphar.2025.178168","DOIUrl":"10.1016/j.ejphar.2025.178168","url":null,"abstract":"<div><div>The objective of this study was to quantify the impact of longitudinal tumour dynamics, time-varying drug-related adverse events (DRAEs), and other clinical characteristics on long-term outcomes in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). An ambispective cohort of 277 patients was analysed and externally validated using independent clinical trial data from 470 patients in the Project Data Sphere. Individual tumour growth trajectories were characterised by predicted sum of the longest diameters (SLD) using tumour growth inhibition (TGI) modelling. Time-dependent Cox and parametric time-to-event models were then applied to evaluate the influence of predicted tumour growth trajectories, observed dynamic DRAE profiles, cross-sectional variables derived from these measures, and additional covariates on time-to-treatment failure (TTF) and progression-free survival (PFS). The TGI models effectively captured individual tumour dynamics. Across both Cox and parametric time-to-event models, prognostic factors consistently included DRAEs, baseline metastasis, EGFR-TKI treatment history, and the specific EGFR-TKI administered. Notably, grade 2 DRAEs were associated with an optimal balance between efficacy and safety, and this association remained robust in sensitivity analyses and was preliminarily validated using external data. These findings emphasise the clinical relevance of DRAE grades in indicating long-term clinical benefit. By linking manageable toxicity with durable therapeutic outcomes, the study provides valuable insights for developing safe and effective EGFR-TKI treatment strategies in patients with NSCLC.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178168"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080055","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}

{"title":"Corrigendum to \"Exploring monoamine oxidase B in nitric oxide dysregulation and vascular disease\" [Europ. J. Pharmacol. 1002 (2025) 1-7 177863].","authors":"Vijay Elipay, Atanu Mandal, Sanjiv Singh","doi":"10.1016/j.ejphar.2025.177903","DOIUrl":"10.1016/j.ejphar.2025.177903","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177903"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599837","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}

{"title":"Resatorvid as a promising neuroprotective agent in pentylenetetrazol-kindling rat model: Suppressing neuroinflammation and enhancing cognitive and motor functions","authors":"Mennatallah H. Zidan,&nbsp;Hanan S. El-Abhar,&nbsp;Samira Saleh ,&nbsp;Nesrine S. El Sayed,&nbsp;Suzan M. Mansour","doi":"10.1016/j.ejphar.2025.178160","DOIUrl":"10.1016/j.ejphar.2025.178160","url":null,"abstract":"<div><div>Toll-like receptor 4 (TLR4) plays a key role in promoting seizure susceptibility, neuronal damage, and network dysfunction in epilepsy through its downstream inflammatory pathways. However, the therapeutic potential of resatorvid, a TLR4 inhibitor remains underexplored. This study investigated the neuroprotective effects of resatorvid (0.25 mg/kg) in a pentylenetetrazole (PTZ)-induced kindling model in rats. Seizures were induced by PTZ (35 mg/kg, every other day, i.p), and once full kindling was established, animals received either resatorvid or the standard antiepileptic drug carbamazepine for 14 days.</div><div>Resatorvid significantly reduced seizure severity, duration, and latency, mirroring the effects of carbamazepine. Using the Morris water maze and open field tests demonstrated improvements in locomotor activity, spatial memory, and cognitive performance. These behavioral gains correlated with hippocampal histopathological improvements, including reduced neuronal damage in the CA1 and CA3 regions as observed via H&amp;E staining.</div><div>At the molecular level, resatorvid treatment downregulated hippocampal protein expression of high mobility group box 1 (HMGB1), TLR4, and its downstream inflammatory signal, phosphorylated-nuclear factor kappa (NF-κ)B p65, and proinflammatory cytokines interleukin (IL)-1β and IL-8, while restoring that of the inhibitory kappa (Iκ)B. In addition, resatorvid reduced glial activation, as evidenced by decreased expression of the astrocytic marker GFAP and microglial marker Iba1 in the cytoplasm. These findings suggest that resatorvid exerts a multimodal neuroprotective effect by attenuating neuroinflammation and glial reactivity, preserving hippocampal structure, and improving cognitive and motor functions. Altogether, the results highlight resatorvid as a promising therapeutic candidate for epilepsy, warranting further exploration in preclinical and clinical settings.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178160"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079992","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}

{"title":"Doxorubicin increases G-protein coupled receptor-mediated vasoconstriction in coronary arteries via the mitogen-activated protein kinase kinase 1/2 pathway","authors":"Caroline Lozahic,&nbsp;Helen Maddock,&nbsp;Mark Wheatley,&nbsp;Hardip Sandhu","doi":"10.1016/j.ejphar.2025.178162","DOIUrl":"10.1016/j.ejphar.2025.178162","url":null,"abstract":"<div><div>Anthracyclines are one of the most effective chemotherapy drugs, but are associated with cardiotoxicity, including hypertension, however, little is known about the effect of anthracyclines on the vascular tone. Emerging data indicate that the anthracycline doxorubicin induces increases in vascular tone via endothelin subtype A (ET_A) and B (ET_B), serotonin (5-HT) subtype 1B (5-HT_1B), and thromboxane prostanoid (TP) G-protein coupled receptors (GPCRs) in coronary arteries. This study examined for the first time whether the mitogen-activated protein kinase kinase 1/2 (MEK 1/2) pathway is involved in the doxorubicin-induced increase of vasoconstriction. This study used an organ culture model, where left anterior descending arteries (LAD) from rats were incubated with doxorubicin (0.5 μM) in the absence and presence of the MEK 1/2 specific inhibitor U0126 (5 μM), and GPCR-mediated vasoconstriction was analysed by wire-myography. GPCR mRNA levels and GPCR expression and localisation on LAD arteries were investigated by real-time PCR and immunohistochemistry. Doxorubicin treatment increased the vasoconstriction through ET_A (278 % increase at 10^−8.5 M endothelin-1 (ET-1), 5-HT_1B (193 % increase at 10^−5.5 M 5-carboxamidotryptamine (5-CT)) and TP (32 % increase at 10^−6.5 M U46619) receptors, and decreased ET_B-mediated vasoconstriction (37 % decrease at 10^−7.5 M Sarafotoxin 6c (S6c)), however, a decrease in ET_B mRNA was detected. Co-incubation with U0126 decreased doxorubicin-mediated increased vasoconstriction through ET_A, 5-HT_1B, and TP receptors. This novel study shows that doxorubicin treatment of LAD arteries increases vasoconstriction through ET_A, 5-HT_1B, and TP receptors through the MEK 1/2 pathway.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178162"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080026","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}