Immunopharmacology and Immunotoxicology最新文献

{"title":"Correction.","authors":"","doi":"10.1080/08923973.2025.2531685","DOIUrl":"https://doi.org/10.1080/08923973.2025.2531685","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600293","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":"ZEB1 silencing protects against ferroptosis and mitochondrial dysfunction in osteoarthritis by inhibiting HSPA5 expression.","authors":"Jie Wan, Feng Shen, Jian Ding, Dong Ye","doi":"10.1080/08923973.2025.2520309","DOIUrl":"https://doi.org/10.1080/08923973.2025.2520309","url":null,"abstract":"<p><strong>Background: </strong>Zinc finger E-box binding homeobox 1 (ZEB1), a ferroptosis-associated gene, is upregulated in osteoarthritis (OA) articular cartilage. However, whether ZEB1 regulates ferroptosis in OA progression remain unclear.</p><p><strong>Methods: </strong>ZEB1 protein levels in cartilage specimens from OA patients and normal controls were measured. Interleukin 1β (IL-1β)-induced chondrocyte injury model was established, followed by short hairpin RNA (shRNA)-mediated ZEB1 silencing in chondrocytes. Chondrocyte viability, apoptosis, inflammatory cytokine expression, extracellular matrix (ECM) degradation were assessed. Moreover, ferrous ion (Fe²⁺) level, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4), mitochondrial membrane potential (MMP) and ATP level were determined. ZEB1-mediated transcriptional regulation of heat shock protein family A member 5 (HSPA5) was validated. Rescue experiments were conducted to validate the ZEB1/HSPA5 regulatory axis in chondrocyte injury. OA mouse model was constructed, and ZEB1 shRNA was injected into OA mice. The pathological changes in cartilage tissues were detected.</p><p><strong>Results: </strong>ZEB1 was upregulated in OA cartilage tissues. ZEB1 silencing attenuated IL-1β-induced apoptosis, inflammation, and ECM degradation. IL-1β treatment increased Fe²⁺, ROS, and MDA levels and decreased GPX4 and GSH levels in chondrocytes, while ZEB1 silencing reversed these changes. ZEB1 silencing abrogated IL-1β-induced MMP and ATP reduction. Mechanistic studies revealed that ZEB1 transcriptionally inhibited HSPA5 expression in chondrocytes. HSPA5 silencing abrogated the protective effects of ZEB1 silencing. Additionally, ZEB1 silencing alleviated articular cartilage degradation, inflammatory response, and iron deposition.</p><p><strong>Conclusion: </strong>ZEB1 silencing ameliorated IL-1β-induced chondrocyte injury and OA progression by suppressing ferroptosis and mitochondrial dysfunction via HSPA5 inhibition.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553404","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":"Anti-inflammatory and immunomodulatory effects of valproate and carbamazepine involve distinct signaling in human peripheral blood mononuclear cells.","authors":"Goran Popović, Sara Rakočević, Miodrag Čolić, Ljiljana Kozić, Marija Drakul, Vanja Mališ, Dejan Bokonjić, Dušan Mihajlović","doi":"10.1080/08923973.2025.2517634","DOIUrl":"https://doi.org/10.1080/08923973.2025.2517634","url":null,"abstract":"<p><strong>Objectives: </strong>Epilepsy is a chronic neurological condition with complex etiopathogenesis, treated with antiepileptics. In addition to their ability to regulate the activation threshold of neurons, antiepileptics have demonstrated a potential in shaping inflammation and the immune response. The main objective of our study was to analyze the effects of valproate, carbamazepine, and lamotrigine (commonly used antiepileptics) on viability, lymphocyte proliferation, and cytokine production by human peripheral blood mononuclear cells (PBMCs).</p><p><strong>Methods: </strong>PBMCs were treated with different concentrations of antiepileptics, with or without phytohemagglutinin (PHA). Cytotoxicity, assessed by viability and apoptosis/necrosis assay, was determined by flow cytometry using the Annexin V/Propidium iodide (PI) staining method. Proliferation was determined using the MTT assay, whereas cytokine levels were assessed by the ELISA assay. A selective peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist (SR-202) was used to evaluate the involvement of PPAR-γ.</p><p><strong>Results: </strong>Nontoxic concentrations of valproate and carbamazepine reduced the levels of three major proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and impaired Th1 and Treg responses, without affecting the Th2 response. Lamotrigine did not exhibit immunomodulatory properties in this model. The effect of valproate on the production of proinflammatory and Th1 cytokines was significantly reversed by inhibiting PPAR-γ. In contrast, the blockade did not modify the effects of carbamazepine.</p><p><strong>Conclusion: </strong>Our results demonstrated that valproate and carbamazepine, although similarly modulating the immune response <i>in vitro</i>, utilize different signaling mechanisms, in contrast to lamotrigine, which did not exhibit immunomodulatory effects.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484117","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":"Adenosine A2B receptor mediates cyclosporine counteraction of inflammatory and renal consequences of sepsis in rats.","authors":"Simone A Salama, Marwa Y Sallam, Sahar M El-Gowilly","doi":"10.1080/08923973.2025.2521005","DOIUrl":"https://doi.org/10.1080/08923973.2025.2521005","url":null,"abstract":"<p><strong>Introduction: </strong>The immunosuppressant drug cyclosporine A (CsA) demonstrates anti-inflammatory properties in numerous pathological conditions. It acts through modulating T-cell receptor signaling, reducing the expression of inflammatory cytokines, and inhibiting mitochondrial permeability, besides modulating vascular response. These features make it a potential drug to prevent or treat septic acute kidney injury (AKI).</p><p><strong>Objective: </strong>In this study, we investigated whether CsA exerts a protective effect against hemodynamic, inflammatory, and renovascular consequences of sepsis and whether these effects are modulated by adenosine receptor signaling.</p><p><strong>Material and methods: </strong>Cecal ligation and puncture (CLP) was utilized to induce sepsis 24 h before hemodynamic and renovascular studies were implicated. Renal vasoconstrictions and vasodilatations were induced by cumulative bolus injections of phenylephrine (PE, 0.41-900 ng) and acetylcholine (ACh, 0.01-7.29 nmol), respectively.</p><p><strong>Results: </strong>The data showed that CsA abrogated CLP-evoked hypotension, tachycardia, and impaired renovascular responsiveness. Similarly, the elevation in kidney biomarkers together with the pro-inflammatory cytokines (Tumor necrosis factor-alpha (TNFα) and Interleukin-6 (IL-6)) were also blunted after CsA administration. Likewise, the elevation in nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and decrease in A2BRs renal tubular expression in sepsis was reversed in CsA-treated rats. These advantageous effects of CsA disappeared upon concurrent exposure to the selective A2BR antagonist, Alloxazine.</p><p><strong>Conclusion: </strong>These results suggest a key role for functional A2BR in CsA counteracting CLP-induced hemodynamic, inflammatory, and renal dysfunction in rats.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325584","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":"Effect of dapagliflozin on sepsis-induced kidney injury in a rat model: modulation of the NLRP3 pathway.","authors":"Ilter Ilhan, Nasıf Fatih Karakuyu, Pınar Karabacak, Adem Milletsever, Oznur Kolay, Gül Baysal, Halil Ascı","doi":"10.1080/08923973.2025.2519597","DOIUrl":"https://doi.org/10.1080/08923973.2025.2519597","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis-induced acute kidney injury (AKI) is a major cause of mortality in critically ill patients. Inflammation, oxidative stress, and apoptosis are key contributors to sepsis-related renal damage. Dapagliflozin (DPG), an SGLT2 inhibitor, has demonstrated anti-inflammatory and nephroprotective effects. This study aimed to investigate the renoprotective effects of DPG in a lipopolysaccharide (LPS)-induced sepsis model, focusing on inflammation, oxidative stress, and apoptosis in the kidneys.</p><p><strong>Methods: </strong>Thirty-two male Wistar albino rats were divided into four equal groups: (1) Control group, which received saline for 5 days; (2) LPS group, which received oral saline for 5 days and a single intraperitoneal LPS injection (5 mg/kg on day 5); (3) LPS+DPG group, which received oral DPG (10 mg/kg/day) for 5 days and a single intraperitoneal LPS injection (5 mg/kg on day 5); (4) DPG group, which received oral DPG (10 mg/kg/day) for 5 days. At the end of the experiment, samples were collected for histopathological, immunohistochemical, biochemical, and genetic analyses.</p><p><strong>Results: </strong>DPG significantly reduced serum urea and creatinine levels, indicating improved renal function. Histopathological analysis of the kidney tissues revealed reduced inflammation, hemorrhage, and necrosis in the LPS+DPG group compared to the LPS group. Also, DPG lowered the expression of pro-inflammatory markers (APAF-1, TNF-α, VCAM-1), reduced oxidative stress (decreased OSI), and downregulated NLRP3, caspase-1, IL-1β, and IL-18 gene expression.</p><p><strong>Conclusion: </strong>Prophylactic DPG administration exerts notable renoprotective effects in sepsis-induced AKI by mitigating inflammation, oxidative stress, and apoptosis. These findings highlight its potential as a preventive strategy, warranting further investigation in therapeutic contexts.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325585","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":"Assessing the effectiveness of camrelizumab plus anti-angiogenesis drug for the treatment of advanced liver cancer: a single‑center retrospective study.","authors":"Fang Lu, Fanrong Wu","doi":"10.1080/08923973.2025.2513481","DOIUrl":"https://doi.org/10.1080/08923973.2025.2513481","url":null,"abstract":"<p><strong>Background: </strong>Camrelizumab has shown encouraging efficacy in advanced liver cancer, either as monotherapy or in combination with chemotherapy; however, there is currently insufficient empirical support for the use of camrelizumab therapy in conjunction with anti-angiogenic drugs to treat intermediate and advanced hepatocellular carcinoma.</p><p><strong>Methods: </strong>Clinical information was gathered retrospectively from patients with intermediate- to advanced-stage hepatocellular carcinoma who were treated with camrelizumab and certain anti-angiogenic drugs at Shanghai Hospital between July 2019 and May 2023.</p><p><strong>Results: </strong>This trial comprised 60 patients with intermediate and advanced hepatocellular carcinoma. Patients receiving first-line therapy had an objective remission rate of 25% (9/36) and a disease control rate of 58.3% (21/36), while those administered second-line therapy and beyond had rates of 12.5% (3/24) and 33.3% (8/24), respectively. Moreover, the median overall survival was 15.17 months (95% CI 12.067, 18.267) and 13 months (95% CI 11.644, 14.356), whereas the median progression-free survival was 7.1 months (95% CI 3.846, 10.354) and 4.67 months (95% CI 2.492, 6.842), respectively. The predominant treatment-emergent adverse events observed during therapy included: elevated total bilirubin in 28 cases (46.7%), proteinuria in 19 cases (31.7%), gastrointestinal reactions in 19 cases (31.7%), and thrombocytopenia in 16 cases (26.7%).</p><p><strong>Conclusion: </strong>Based on real-world data, individuals with intermediate and advanced primary liver cancer undergoing systemic therapy may benefit from camrelizumab combined with anti-angiogenic drugs.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301984","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":"Dichapetalin-type triterpenoids inhibits macrophage interferon expression by regulating the cGas-STING pathway, suggesting potential application in immunosuppression.","authors":"Chuan Zhao, Yi-Ming Sun, Guo-Rong Li, Yue Wang, Yu-Rong Da, Sheng-An Tang, Long Li","doi":"10.1080/08923973.2025.2513476","DOIUrl":"10.1080/08923973.2025.2513476","url":null,"abstract":"<p><strong>Background: </strong>Dichapetalin-type triterpenoids (DTs) derived from <i>Dichapetalum longipetalum</i> (Turcz.) Engl. have attracted extensive attention due to their novel structure, as well as potent anti-tumor and anti-inflammatory activities. In this study, the immunosuppressive effect of Dichapetalin-type triterpenoids on mouse peritoneal macrophages (MPMs) was studied.</p><p><strong>Methods: </strong>MPMs were stimulated with HSV-1 or LPS for the inflammation model. The cytokines and inflammatory mediators were detected by RT-PCR. Western blotting was carried out to determine the phosphorylation of TBK1 and IRF3.</p><p><strong>Results: </strong>Our results showed that DTs inhibited the expression of IFN-β in MPMs infected with HSV-1, and also inhibited the expression of Il-1β and Il-6 in LPS-stimulated MPMs. In addition, compound <b>1</b> (dichapetalin A) down regulated the phosphorylation of Tbk1 and Irf3 in HSV-1-infected MPMs.</p><p><strong>Conclusion: </strong>Taken together, this study suggests that DTs isolated from the <i>Dichapetalum longipetalum</i> (Turcz.) Engl. inhibits macrophage activation through the cGas-STING pathway in MPMs, which would be potential for the treatment of autoimmune diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181491","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":"Immune checkpoint inhibitors and immunosuppressive tumor microenvironment: current challenges and strategies to overcome resistance.","authors":"Gurpreet Singh Gill, Simmi Kharb, Gitanjali Goyal, Prasenjit Das, Kailash Chand Kurdia, Ruby Dhar, Subhradip Karmakar","doi":"10.1080/08923973.2025.2504906","DOIUrl":"10.1080/08923973.2025.2504906","url":null,"abstract":"<p><strong>Objectives: </strong>Immune checkpoint inhibitors (ICIs) are shown to improve cancer treatment effectiveness by boosting the immune system of the patient. Nevertheless, the unique and highly suppressive TME poses a significant challenge, causing heterogeneity of response or resistance in a considerable number of patients. This review aims to explore the challenges posed by the immunosuppressive tumor microenvironment (TME) in response to immune checkpoint inhibitors (ICIs) and discusses potential strategies to overcome resistance.</p><p><strong>Material & methods: </strong>A comprehensive review of existing literature was conducted to analyze the immunosuppressive features of the TME, including the role of immunosuppressive cells, cytokine and chemokine signaling, metabolic alterations, and overexpression of immune checkpoint molecules (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, BTLA). Additionally, strategies to overcome resistance-such as targeting immunosuppressive cells, normalizing tumor vasculature, dual or triple checkpoint blockade, and combining ICIs with vaccines, oncolytic viruses, and metabolic inhibitors-are elaborated. The need for predictive biomarkers to stratify patients and assess treatment response was also discussed.</p><p><strong>Results: </strong>The review highlights that the immunosuppressive TME contributes significantly to resistance against ICIs, mediated through various mechanisms. Potential strategies to overcome resistance include modulating the TME by targeting immunosuppressive components, combination therapies, and the identification of predictive biomarkers. Further research and innovative approaches are required to fully understand TME-ICI interactions and change the face of cancer treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-23"},"PeriodicalIF":2.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077827","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":"Punicalagin ameliorates lipopolysaccharide-induced inflammatory response in dental pulp cells via inhibition of the NF-κB/Wnt5a-ROR2 pathway.","authors":"Yumeng Yang, Ke Deng, Shan Jiang, Xiaolan Guo, Yiming Zhong, Buling Wu, Liu Wei","doi":"10.1080/08923973.2025.2470343","DOIUrl":"10.1080/08923973.2025.2470343","url":null,"abstract":"<p><strong>Introduction: </strong>Punicalagin (PCG) is a major polyphenolic component with potent anti-inflammatory, anti-atherogenic, anti-cancer, and antioxidant activities. This study aimed to investigate the impact and underlying mechanisms of PCG on lipopolysaccharide (LPS)-induced dental pulpitis.</p><p><strong>Methods: </strong>A rat pulpitis model was constructed, and the infected pulp was covered with a PCG collagen sponge. <i>In vitro</i>, dental pulp cells (DPCs) were isolated, and the effects of LPS and PCG on cell viability were assessed. The expression levels of inflammation-related factors were investigated by qRT-PCR and ELISA. The Nuclear Factor kappa B (NF-κB) transcription factors and Wnt family member 5a-Receptor tyrosine kinase like Orphan Receptor 2 (Wnt5a-ROR2) levels were evaluated by immunofluorescence staining and Western blotting.</p><p><strong>Results: </strong>We demonstrated that the PCG collagen sponge effectively reduced the infiltration of inflammatory cells in the pulp. PCG significantly alleviated the inflammatory response by reducing the mRNA expression levels of IL-1β, IL-6, IL-8, ICAM-1, and VCAM-1 and the secretion of IL-6 and IL-8 in a concentration-dependent manner. Immunofluorescence staining showed that the activation of the NF-κB pathway was hindered by PCG, which affected with the nuclear translocation of P65. PCG reduced the phosphorylation levels of P65 and IκBα and suppressed the expression levels of Wnt5a and ROR2 induced by LPS. The NF-κB inhibitor Bay11-7082 reduced the activation of the NF-κB/Wnt5a-ROR2 pathway and the inflammatory response; the application of PCG significantly augmented this inhibitory effect.</p><p><strong>Discussion: </strong>PCG demonstrated an anti-inflammatory effect in LPS-induced DPCs by targeting the NF-κB/Wnt5a-ROR2 signaling pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"317-327"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491896","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":"Vildagliptin attenuates doxorubicin-induced hepatotoxicity via activating Nrf2/HO-1 and SIRT1 and suppressing NF-κB signals in rats.","authors":"Heba M Mahmoud, Emad H M Hassanein, Marwa M Khalaf","doi":"10.1080/08923973.2025.2482863","DOIUrl":"10.1080/08923973.2025.2482863","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is an anticancer commonly employed in cancer treatment. However, the clinical application of DOX is associated with hepatotoxicity. Vildagliptin is an anti-hyperglycemic agent that inhibits the dipeptidyl peptidase-4 enzyme. Besides being used in managing type-2 diabetes, vildagliptin showed potential anti-inflammatory, antioxidant, and other activities.</p><p><strong>Objective: </strong>Our investigation targeted the hepatoprotective effects of vildagliptin against DOX-induced hepatotoxicity.</p><p><strong>Methods: </strong>Vildagliptin was given in a dose of 30 mg/kg, once daily; p.o. for 2 weeks while DOX was injected in a single dose of 30 mg/kg, i.p.</p><p><strong>Results: </strong>Vildagliptin effectively decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, while it effectively elevated serum total protein (TP) level. Histologically, vildagliptin administration resulted in significant hepatoprotective efficacy with abundant figures of normal hepatocytes. Moreover, vildagliptin considerably decreased lipid peroxidation biomarker malondialdehyde (MDA), and the cytokines interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2, while it remarkably boosted the antioxidative defenses of glutathione (GSH) and catalase (CAT). Dual antioxidant and anti-inflammatory activities were mediated by upregulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2), silent information regulator 1 (SIRT1), and heme oxygenase (HO-1) and suppressing the nuclear factor kappa B (NF-κB) signals. Finally, vildagliptin alleviated apoptosis by downregulating hepatic p53 and cytochrome (Cyt)-C.</p><p><strong>Conclusion: </strong>Our findings suggest that vildagliptin improved hepatocellular architecture and reduced hepatic oxidative injury, inflammation, and apoptosis associated with DOX treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"364-374"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730081","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}