Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Mitochondrial Oxidative Stress and Cardiac Dysfunction in TERT Deficient Progeria Mice","authors":"Zandong Zhou, Yunpeng Zhang, Rui Zhao, Daiqi Liu, Bingxin Xie, Qingling Zhang, Gary Tse, Feng Wang, Tong Liu","doi":"10.1111/1440-1681.70082","DOIUrl":"https://doi.org/10.1111/1440-1681.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heart failure (HF) is a major cause of hospitalisation in the elderly. Its incidence increases with aging and the presence of risk factors such as hypertension and diabetes. Aging-related myocardial fibrosis, characterised by alterations in the extracellular matrix and myocardial structure, leads to impairment of cardiac function. However, the specific mechanisms linking mitochondrial oxidative stress to cardiac remodelling in aging remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To elucidate the mechanisms underlying aging-related ventricular electrical and structural remodelling and to determine the role of mitochondrial dysfunction in modulating aging-associated HF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We developed third-generation homozygous telomerase reverse transcriptase deficient (TERT<sup>−/−</sup>) progeria mice to model accelerated aging. Compared to wild-type controls, these mice exhibited marked upregulation of aging-associated genes and proteins such as p53 in ventricular tissue. Echocardiographic analysis revealed significant reductions in left ventricular ejection fraction and fractional shortening, indicating both systolic and diastolic dysfunction. Histological staining showed increased interstitial fibrosis and inflammatory cell infiltration, which correlated with elevated expression of fibrosis markers including collagen type I and TGF-β. Electrocardiography and epicardial mapping demonstrated prolonged QRS duration and slowed ventricular conduction velocity. These findings, together with increased conduction heterogeneity, are indicative of electrical remodelling. Furthermore, RNA sequencing and biochemical assays identified upregulation of mitochondrial oxidative stress pathways and elevated levels of malondialdehyde and MnSOD, alongside disrupted mitochondrial ultrastructure and downregulation of mitochondrial dynamics-related proteins such as MFN2 and Drp1. These findings highlight the central role of mitochondrial dysfunction in driving structural and electrical cardiac remodelling in aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings demonstrate that third-generation TERT<sup>−/−</sup> senescent mice exhibit significant cardiac impairments, including electrical remodelling, structural changes, and mitochondrial dysfunction, suggesting mitochondrial oxidative stress may be related to aging-related HF. These insights underscore the potential of targeting mitochondrial dysfunction for therapeutic strategies in aging-related HF. Collectively, these data demonstrate that telomerase deficiency drives cardiac structura","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 12","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284550","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":"Combination of Tanshinone IIA and Matrine Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Supressing Ferroptosis via Nrf2/HO-1 Pathway Activation","authors":"Huanqing Xiong,&nbsp;Yujuan Li,&nbsp;Jiaying Gao,&nbsp;Jian Chen,&nbsp;Gang Liu,&nbsp;Faguang Jin","doi":"10.1111/1440-1681.70072","DOIUrl":"10.1111/1440-1681.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions that involve severe lung inflammation leading to respiratory failure. Tanshinone IIA (TIIA) and Matrine (MAT), two herbal medicinal compounds, have been reported to exhibit several similar pharmacological properties including anti-inflammatory, antioxidant, and anticancer effects. Although previous studies have reported the combined therapeutic efficacy of using two drugs in treating ALI, it remains unknown whether TIIA and MAT have any synergistic effect in alleviating ALI/ARDS. Therefore, this study investigated whether a combined therapy of TIIA and MAT has protective effects against lipopolysaccharide (LPS)-induced ALI and its mechanism of action using mouse and cell models. The results showed that the TIIA + MAT combination ameliorated ALI by reducing edema, tissue injury, and proinflammatory cytokine secretion. This therapy enhanced antioxidant defences, as indicated by upregulated GPX4 and SLC7A11 levels, decreased 4-HNE and ROS levels, and ferroptosis inhibition. Furthermore, TIIA + MAT promoted Nrf2 nuclear translocation, leading to increased HO-1 expression and an anti-oxidative response. These findings suggest that the combination of TIIA and MAT alleviates LPS-induced ALI by inhibiting ferroptosis via activation of the Nrf2/HO-1 pathway. Thus, the co-administration of TIIA and MAT may be an effective therapeutic strategy for ALI, potentially offering a novel clinical approach to mitigate ferroptosis and inflammation.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250346","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":"The Health Education During Root Canal Therapy Reduces the Use of Antibiotics","authors":"Ting Yi,&nbsp;Fan Gu,&nbsp;Shengbo Liu,&nbsp;Qiaowen Li,&nbsp;Li Wang,&nbsp;Wei Yin","doi":"10.1111/1440-1681.70083","DOIUrl":"10.1111/1440-1681.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>Although antibiotics can effectively control infectious diseases, overuse of antibiotics can cause problems such as drug resistance. Pulpitis and apical periodontitis are among the most common infectious diseases in humans. To alleviate the intense tooth pain, patients often self-administer antibiotics. To guide patients in managing pulpitis and apical periodontitis more effectively, we designed a Root Canal Treatment Health Education Form and provided personalised guidance on antibiotic use during the treatment period. From January 2024 to March 2025, a total of 272 patients participated in this project. Benefiting from health education, the proportion of antibiotic use was significantly lower compared to the control group. Both patients and healthcare professionals involved in this health education program held positive attitudes towards the intervention. Our experience suggested that health education should be actively promoted in the treatment of pulpitis and apical periodontitis.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243525","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":"Indole-3-Propionic Acid Improves Vascular Function in High-Fat Diet-Induced Obese Mice via eNOS","authors":"Shaying Yang,&nbsp;Zhiwei Wang,&nbsp;Xin Wen","doi":"10.1111/1440-1681.70081","DOIUrl":"10.1111/1440-1681.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The gut microbiota-derived metabolite indole-3-propionic acid (IPA) has been implicated in vascular homeostasis; however, its role in mesenteric vascular function and blood pressure regulation under obese conditions remains unclear. This study aimed to investigate the effects of IPA on mesenteric vascular endothelial function and blood pressure in high-fat diet-induced obese (DIO) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C57BL/6 mice were fed a high-fat diet for 3 months to induce the DIO model. DIO mice were gavaged daily with IPA (20 mg/kg) for 6 weeks. At the end of the treatment, inflammatory markers and nitric oxide (NO) levels in primary mesenteric artery endothelial cells were assessed by qPCR and fluorescence staining, respectively. Vascular relaxation function of the mesenteric arteries was measured via wire myograph. Additionally, the immediate effect of IPA on blood pressure was monitored via the tail-cuff method following IPA injection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrated that IPA treatment significantly reduced the levels of inflammatory cytokines in the endothelial cells of DIO mice. IPA administration markedly increased NO levels in endothelial cells and enhanced the endothelium-dependent vasodilation of mesenteric arteries. Mechanistically, IPA enhanced the phosphorylation of endothelial nitric oxide synthase (eNOS) via the PI3K/Akt pathway, promoting the production and release of NO, thereby regulating blood pressure. This was further validated in eNOS^−/− mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals the vascular protective effects of IPA in obesity, providing new insights for the treatment of obesity-related cardiovascular diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243461","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":"Correction to “Glaucocalyxin A Induces Apoptosis of Non-Small Cell Lung Carcinoma Cells by Inhibiting the PI3K/Akt/GSK3β Pathway”","authors":"","doi":"10.1111/1440-1681.70080","DOIUrl":"10.1111/1440-1681.70080","url":null,"abstract":"<p>D. Zhang, T. Deng, W. Yuan, T. Chen, and S. Jiang, “Glaucocalyxin A Induces Apoptosis of Non-Small Cell Lung Carcinoma Cells by Inhibiting the PI3K/Akt/GSK3β Pathway,” <i>Clinical and Experimental Pharmacology and Physiology</i> 49, no. 8 (2022):797-804.</p><p>In Figure 3, an incorrect image was inadvertently incorporated during the final graphical assembly process due to erroneous file selection. The correct figure is shown below.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231618","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":"Kisspeptin-10 Preserves the Blood-Brain Barrier's Integrity Post-Stroke by Augmenting Claudin-10 Expression","authors":"Liming Li,&nbsp;Yunlong Guo,&nbsp;Kaijie Zhao","doi":"10.1111/1440-1681.70079","DOIUrl":"10.1111/1440-1681.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>The integrity of the Blood-Brain Barrier (BBB) is crucial in the pathophysiological progression of acute ischemic stroke (AIS). However, the potential of Kisspeptin-10 (Kp-10), with its antioxidant and anti-inflammatory properties, has not been explored experimentally in the context of stroke management. This study aimed to investigate the neurovascular protective effects of Kp-10 following cerebral ischemia using both in vivo and in vitro models. A middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice, followed by Kp-10 administration. Neurological deficits (Longa score), infarct volume (TTC staining), BBB permeability (14C-Sucrose), and Claudin-10 expression (qRT-PCR and immunohistochemistry) were assessed to evaluate the therapeutic effects of Kp-10. Human brain microvascular endothelial cells (HBMVECs) were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) to mimic ischemic conditions. Endothelial permeability, oxidative stress (OS), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels were evaluated. Nrf2 silencing was performed to validate its role in Kp-10-mediated protection. Initially, we observed a significant reduction in Kp-10 expression within the cortical tissue of mice subjected to MCAO. Subsequent administration of Kp-10 not only alleviated neurological deficits but also significantly mitigated blood–brain barrier (BBB) dysfunction following stroke induction, as evidenced by reduced 14C-sucrose leakage. Furthermore, Kp-10 treatment led to an upregulation of Claudin-10 expression in the post-stroke cortical region. In our in vitro experiments, we employed HBMVECs exposed to OGD/R to simulate ischemic conditions. We found that Kp-10 effectively reduced OGD/R-induced endothelial permeability by enhancing Claudin-10 expression. Additionally, Kp-10 exhibited antioxidant capabilities by decreasing mitochondrial reactive oxygen species (ROS) levels, increasing superoxide dismutase (SOD) activity, and upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Notably, when Nrf2 was knocked down in HBMVECs, the protective effects of Kp-10 on endothelial permeability and Claudin-10 expression were abolished, indicating that the beneficial actions of Kp-10 are mediated through the Nrf2 pathway. In conclusion, our findings suggest that Kp-10 holds promise as a therapeutic strategy to preserve BBB integrity and promote neuroprotection following stroke, acting primarily via the Nrf2 signalling pathway. These findings suggest that Kp-10 may represent a promising therapeutic strategy for preserving BBB integrity following ischemic stroke.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191135","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":"Activation of GPR39 Ameliorates Placental Dysfunction by Inhibiting Activation of NLRP1 Inflammasome in Gestational Diabetes Mellitus","authors":"Xiaohua Zhou,&nbsp;Hong Sun","doi":"10.1111/1440-1681.70074","DOIUrl":"10.1111/1440-1681.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) is a metabolic condition defined by glucose intolerance during pregnancy, which frequently results in placental malfunction, oxidative stress, and chronic inflammation, all of which are linked to the activation of the NLRP1 inflammasome. GPR39, a G protein-coupled receptor, has emerged as a possible therapeutic target, and its agonist, TC-G 1008, may provide protection against metabolic disorders. In this study, we investigated the expression of GPR39 in the murine placenta and its role in GDM-related placental dysfunction using a high-fat diet-induced GDM mouse model. Mice were treated with TC-G 1008 (7.5 and 15 mg/kg) from gestational day 0 to 18, and placental tissues were analysed via RT-PCR, Western blot, immunohistochemistry, ELISA, and biochemical assays. Our findings indicated that GPR39 expression was markedly reduced in GDM mice relative to wild-type controls. Administration of TC-G 1008 (7.5 and 15 mg/kg) enhanced fetal outcomes, including survival rate, weight, and crown-rump length, while also mitigating maternal metabolic disorders such as hyperglycaemia, insulin resistance, and dyslipidaemia. Moreover, the administration of TC-G 1008 mitigated placental oxidative stress by augmenting SOD activity and GSH levels, while inhibiting NLRP1 inflammasome activation, as shown by diminished expression of NLRP1, ASC, and Caspase-1, alongside lowered levels of IL-1β and IL-18. Furthermore, GPR39 activation suppressed the NF-κB and MAPK signalling pathways. These findings suggest that GPR39 activation by TC-G 1008 ameliorates placental dysfunction in GDM by mitigating oxidative stress and inflammation via suppression of the NLRP1 inflammasome, highlighting its potential as a therapeutic strategy for GDM-associated complications.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091241","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":"Overexpression of miR-718 in Keratinocytes Affects the Psoriatic Inflammation via Targeting STAT1: In Vitro and In Vivo Evidence","authors":"Himani Rani,&nbsp;Neeru Saini","doi":"10.1111/1440-1681.70073","DOIUrl":"10.1111/1440-1681.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is a complex inflammatory autoimmune skin illness that causes epidermal keratinocyte hyperproliferation and dedifferentiation. In a previous study we did in the lab, we found that treating human keratinocytes (HaCaT) with PUVA increased the expression of hsa-miR-718 compared to control. In this study, an imiquimod (IMQ)-induced mouse model and HaCaT were used to look at how overexpressing miR-718 could help treat psoriasis and its causes. To gain more understanding, the in vivo study used the JAK1/3 inhibitor tofacitinib. We observed that miR-718 overexpression leads to the inhibition of JAK–STAT signalling, as evidenced by the reduced expression of STAT1, JAK proteins, and their phosphorylated forms, both in vitro and in vivo<i>.</i> Luciferase assay demonstrated the direct inhibition of STAT1 due to miR-718 overexpression. Additionally, in vitro experiments showed downregulation of STAT2 and STAT3. Inhibition of basal miR-718 in HaCaT overactivates JAK–STAT signalling proteins. In psoriatic mice, ectopic miR-718 reduces NF-kB, a key mediator of inflammation. IHC shows lower acanthosis and parakeratosis in IMQ-induced psoriatic mice. In the skin of mice that had been miR-718 transfected, there was less VEGF, MMP7 and MMP9. Understanding how miR-718 improves psoriasis not only provides new information but also inspires hope for its potential use as a psoriasis treatment.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084928","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":"Kaempferol Ameliorates Sepsis-Acute Lung Injury by Promoting Succinylation of SRPK1","authors":"Yuan Zhang,&nbsp;Huilin Liu,&nbsp;Yan Jin","doi":"10.1111/1440-1681.70077","DOIUrl":"10.1111/1440-1681.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis is the leading cause of acute lung injury (ALI), and kaempferol has a protective effect against ALI. However, the underlying mechanisms have not been fully elucidated. This study aimed to investigate the role of kaempferol in sepsis-induced ALI and its underlying molecular mechanism, particularly the involvement of succinylation. Human pulmonary microvascular endothelial cells were treated with lipopolysaccharide to induce injury. Cell apoptosis and inflammation were evaluated by flow cytometry and enzyme-linked immunosorbent assay. Succinylation was analysed using immunoblotting, co-immunoprecipitation and protein stability assay. The results showed that kaempferol inhibited apoptosis and inflammation response in LPS-treated HPMVECs and attenuated lung damage in septic mice. Moreover, kaempferol enhanced succinylation levels and reduced SIRT5 protein levels. SIRT5 suppressed the succinylation of SRPK1 at lysine (K) 588 site and facilitated SRPK1 degradation. Overexpression of SIRT5 or knockdown of SRPK1 reversed the inhibitory effects of kaempferol or SIRT5 knockdown on cellular biological behaviours, respectively. In conclusion, kaempferol attenuates sepsis-induced lung injury by inhibiting HPMVEC apoptosis and inflammation. Mechanistically, kaempferol suppresses SIRT5-mediated desuccinylation of SRPK1, thereby promoting SRPK1 protein stability. The findings suggest the important role of SRPK1 succinylation in ALI and kaempferol may be used for the treatment of the disease.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074635","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":"Rufinamide Mitigates Seizures and Behavioural Deficits via BDNF/TrkB Modulation and Oxidative Stress Reduction in Pentylenetetrazole-Kindled Mice","authors":"Saima Abbas,&nbsp;Abida Parveen,&nbsp;Waseem Ashraf,&nbsp;Syed Muhammad Muneeb Anjum,&nbsp;Rana Muhammad Zahid Mushtaq,&nbsp;Faleh Alqahtani,&nbsp;Imran Imran","doi":"10.1111/1440-1681.70075","DOIUrl":"10.1111/1440-1681.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rufinamide (RUF) is a 3rd generation antiseizure medication (ASM) with a triazole ring that blocks voltage-gated sodium channels (VGSCs) and is most commonly used to treat Lennox–Gastaut syndrome. Thus, the present study examined the effect of RUF on EEG activity, behavioural testing, oxidative stress, and mRNA expression in PTZ-kindled mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male BALB/c mice were administered rufinamide (30, 60, and 90 mg/kg) for 21 days along with 11 injections of PTZ (40 mg/kg) given every other day. EEG recordings were monitored and a series of behavioural tests after RUF treatment were done to assess the post-kindling associated anxiety and memory impairment. We also assessed the oxidative alterations, variation in real-time BDNF/TrkB mRNA expression as well as neuroinflammatory markers in isolated mice brains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of results showed that RUF at the dose of 90 mg/kg maximally suppressed the progression of full-bloom seizures and decreased cortical epileptic spike discharge. Moreover, RUF showed significant anxiolytic action and prevented PTZ-induced cognitive decline in a dose-dependent manner. Because of its anti-inflammatory and antioxidant properties, RUF decreased lipid peroxidation, AChE activity, raised glutathione and superoxide dismutase levels in the mice brain. RUF suppressed the PTZ-induced upregulation of BDNF/TrkB signalling and significantly reduced pro-inflammatory cytokines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It is possible that the effects of RUF that have been seen are the consequence of decreased oxidative stress, BDNF/TrkB downregulation, and reduced expression of neuroinflammatory markers, which in turn reduce ictogenesis and improve the neuropsychiatric consequences associated with epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074620","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}