Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.","authors":"Joachim Neumann, Britt Hofmann, Ulrich Gergs","doi":"10.1007/s00210-025-04029-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04029-7","url":null,"abstract":"<p><p>The calcitonin gene-related peptide (CGRP) is an endogenous peptide that is known to be involved in the development of a migraine. CGRP is also present in the human heart, acts via CGRP receptors, and has been shown to increase the force of contraction (FOC) in isolated, electrically driven human atrial preparations (HAP) from adult patients obtained during open-heart surgery. Here, the hypothesis was tested that the positive inotropic effect (PIE) of CGRP could be attenuated by three anti-migraine drugs, namely ubrogepant, erenumab (both CGRP receptor antagonists), and eptinezumab (a CGRP antagonist). CGRP, cumulatively applied at concentrations ranging from 1 to 100 nM, increased the FOC. In the presence of cilostamide, an inhibitor of phosphodiesterase III, CGRP was more potent and effective than in the absence of cilostamide. Furthermore, when 100 nM CGRP was administered, subsequent application of ubrogepant (1 nM), erenumab (2 nM), and eptinezumab (6 nM) led to a reduction of FOC in HAP. In a more effective way, 1 µM carbachol and 1 µM (-)-N⁶-phenylisopropyladenosine (PIA) attenuated the PIE of CGRP in the presence of cilostamide. Conversely, when we applied first ubrogepant (1 nM), erenumab (2 nM), or eptinezumab (6 nM), then, this pre-incubation attenuated the PIE in HAP of cumulatively applied CGRP compared to CGRP given alone. We conclude that ubrogepant, erenumab, and eptinezumab are functional antagonists of CGRP in HAP at therapeutic concentrations of these anti-migraine drugs. Further investigation is necessary to determine whether this reduction in FOC is beneficial or detrimental for migraine patients.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630644","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":"Ameliorative and protective effects of coenzyme Q10 against natural and chemical toxicity: a narrative review.","authors":"Majid Keshavarzi, Karim Naraki, Bibi Marjan Razavi, Hossein Hosseinzadeh","doi":"10.1007/s00210-025-03992-5","DOIUrl":"https://doi.org/10.1007/s00210-025-03992-5","url":null,"abstract":"<p><p>Coenzyme Q10 (CoQ10) or ubiquinone is the most known dietary and nutritional supplementation, which has various functions in the body such as involvement in adenosine triphosphate production, modulation of gene expression, antioxidant, and anti-inflammatory effects. It has been indicated that it is useful against cardiotoxicity, hepatotoxicity, neurotoxicity, nephrotoxicity, and so on, which are induced by various toxicants. In this review, we selected articles that include the protective effects of CoQ10 against the toxicity of various chemical and natural compounds including pharmaceuticals, metals, pesticides, etc. Scientific databases including PubMed/Medline, Science Direct, Scopus, and Google Scholar were searched to find relevant in vitro and in vivo studies. The underlying protective mechanisms for CoQ10 against natural and chemical compound toxicity included the enhancement of antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and suppression of pro-inflammatory markers such as tumor necrosis factor-alpha, interleukin-1, and IL-6. Furthermore, it has anti-apoptotic potential by regulating the B-cell lymphoma, Bcl-2-associated X protein, and caspase3/9. Overall, these properties make CoQ10 a highly fascinating compound that may contribute to different aspects of health.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625335","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":"Novel drug delivery systems in topical treatment of atopic dermatitis.","authors":"Meghna Dabhadkar, Madhur Kulkarni","doi":"10.1007/s00210-025-04002-4","DOIUrl":"https://doi.org/10.1007/s00210-025-04002-4","url":null,"abstract":"<p><p>Atopic dermatitis (AD), also known as eczema, is a chronic skin condition, affecting all ages, characterized by inflammation, itching, dryness, and redness, which can severely impact quality of life. Based on clinical features and symptoms, AD is of several types like contact dermatitis, dyshidrotic eczema, neurodermatitis, seborrheic dermatitis, stasis dermatitis, and nummular eczema. Its pathophysiology involves genetic, environmental, and immunological factors, leading to skin barrier dysfunction. Current treatments for AD involve a combination of pharmacological and non-pharmacological strategies tailored to individual needs. Management includes topical therapies of corticosteroids, calcineurin inhibitors, phosphodiesterase inhibitors, and janus kinase inhibitors in the form of gels, creams, ointments, and lotions. Systemic treatments like immunosuppressants and biologics are employed for severe cases. Long term and regular use of current treatments can lead to numerous adverse effects like skin thinning, atrophy, burning sensation, emergence of skin lymphomas, tolerance, and systemic side effects. Emerging topical nanoformulations, such as lipid-based nanoparticles, polymeric carriers, liposomes, cubosomes, ethosomes, nanoemulsions enhance drug delivery, improve therapeutic outcomes, and reduce toxicity, making them promising options for AD treatment. Clinical trials of nanoformulations for AD show significant improvements in treatment efficacy and skin absorption compared to conventional therapies. However, nanomedicine faces challenges in terms of inadequate evaluation studies and formulation instability, requiring stringent regulatory compliance and a thorough preclinical and clinical data investigation. This review aims to describe types of AD, its pathophysiology and current treatments and their challenges. The review further focuses on emerging trends of various nanoformulations for treatment of AD.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625344","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":"Trans-sodium crocetinate attenuates acute kidney injury induced by rhabdomyolysis in rats: focusing on PI3K/AKT, apoptosis, and autophagy pathways.","authors":"Tahereh Aminifard, Soghra Mehri, Abolfazl Khajavirad, Zahra Moosavi, Sara Hosseinian, Hossein Hosseinzadeh","doi":"10.1007/s00210-025-03910-9","DOIUrl":"https://doi.org/10.1007/s00210-025-03910-9","url":null,"abstract":"<p><p>Rhabdomyolysis (RM) is a clinical disorder characterized by the release of potentially toxic muscle cell components into the bloodstream, with acute kidney injury (AKI). Trans-sodium crocetinate (TSC) is derived from the carotenoid crocetin known for its renoprotective, anti-inflammatory, and antioxidant properties. This study aimed to assess the protective effects of TSC on RM-induced AKI in rats. Six groups of rats (n = 6) were used: control, AKI (50% glycerol 10 mL/kg, intramuscularly), AKI treated with TSC (10, 20, and 40 mg/kg, intraperitoneally), and TSC (40 mg/kg) alone groups. Two days after the initial injection, urine and blood samples were collected over 24 h to investigate creatine phosphokinase (CPK), kidney function markers, and electrolyte levels. Additionally, kidney tissue was collected to assess renal oxidative markers, histological alterations, and the expression of protein markers related to autophagy, apoptosis, renal injury, inflammation, and the PI3K/AKT signaling pathway. After glycerol administration, there was an increase in oxidative stress, autophagy, apoptosis, renal injury, and inflammatory marker levels, accompanied by a decrease in the proteins of the PI3K/AKT signaling pathway in the kidney. The co-administration of TSC with glycerol resulted in the improvement of renal dysfunction and structural abnormalities, achieved through a reduction in oxidative stress. TSC also down-regulated autophagy, apoptotic, renal injury, and inflammatory markers. Furthermore, TSC treatment led to a decrease in the renal expression of PI3K/AKT signaling pathway proteins. In conclusion, TSC exhibited a protective effect against RM-induced AKI by modulating oxidative stress, autophagy, apoptosis, and the PI3K/AKT pathway.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625345","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":"Neuroprotection in traumatic brain injury: effects of alpha-asarone and Acorus calamus extract in mice using weight drop model.","authors":"Sunishtha Kalra, Himanshu Sachdeva, Aditya Bhushan Pant, Govind Singh","doi":"10.1007/s00210-025-03977-4","DOIUrl":"https://doi.org/10.1007/s00210-025-03977-4","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a significant public health concern characterized by severe neurological consequences. The management of TBI remains a formidable challenge, necessitating a multifaceted approach aimed at reducing secondary injury and promoting neuroprotection. This study assessed the neuroprotective potential of Alpha-asarone (AA) at 12.5, 25, 50 mg/kg, p.o (phytoconstituent of Acorus calamus) at, and Acorus calamus (AC) extract at 190 mg/kg, p.o in a murine TBI model induced by weight drop method. Blood-Brain Barrier (BBB) permeability and oxidative stress were evaluated on 1^st and 3^rd day, while Neurological Severity Score (NSS) was assessed on 1^st, 3^rd, 7^th, 14^th, and 21^st day after TBI. The administration of AA and AC extract at all tested doses demonstrated a dose-dependent restoration of blood-brain barrier (BBB) integrity and oxidative stress markers. Specifically, AA at doses of 25 mg/kg and 50 mg/kg, as well as AC extract at 190 mg/kg, administered orally, exhibited significant effects on BBB integrity and oxidative stress at 1^st and 3^rd day post-treatment. Furthermore, enhanced neurological outcomes were observed at 14^th and 21^st day post TBI, evidenced by improved NSS, particularly with the 50 mg/kg dose of AA and the 190 mg/kg dose of AC extract. This research underscores the potential of AA and AC extract as neuroprotective agents. The findings highlight their efficacy in improving BBB integrity, mitigating oxidative stress-induced cellular damage and enhancing neurological impairments following TBI. These results hold promise for the development of innovative neuroprotective therapies and advocate for the exploration of natural compounds as adjunctive interventions in TBI management.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625340","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":"Exploring mechanisms of britannin against colorectal cancer based on experimentally validated network pharmacology.","authors":"Xiaoli Liu, Qiuxia Ye, Mengdi Hao, Huimin Li, Dajin Yuan, Wenbin Huang, Wenjie Li, Lei Ding","doi":"10.1007/s00210-025-03995-2","DOIUrl":"https://doi.org/10.1007/s00210-025-03995-2","url":null,"abstract":"<p><p>Britannin is an active compound derived from Inula japonica Thunb. that possess a wide range of pharmacological activities. However, the mechanism underlying its influence on colorectal cancer (CRC) is not clear. This study aimed to explore the mechanism of britannin in treating colorectal cancer. We employed network pharmacology and single-cell RNA sequencing to assess the potential mechanism of britannin in CRC therapy. In vivo and in vitro experiments were conducted to confirm the effect of britannin on CRC cells and tumor environment. Network pharmacology analysis identified 36 britannin-related genes associated with CRC. Key signaling pathways, including the PI3K-Akt pathway, PD-L1 expression, and HIF-1 signaling, were implicated in britannin's anti-CRC effects. CIBERSORT and scRNA-seq analyses revealed that britannin affects tumor cells, macrophages, and endothelial cells, with a particular impact on macrophage polarization. In vitro assays confirmed that britannin suppressed CRC cell proliferation, promoted apoptosis, and inhibited AKT phosphorylation. In vivo, britannin significantly suppressed tumor growth and modulated the tumor microenvironment by inhibiting M1 macrophage polarization. Britannin may inhibit colorectal by directly inhibiting colon cancer cells and modulating macrophage polarization.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625337","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":"Potential prognostic biomarker of OSBPL10 in pan-cancer associated with immune infiltration.","authors":"Jiapeng Qi, Kun Yu, Bei Liu, Yan Wang, Wei Wang, Ran An, Chaojun Wang, Na Li, Dongqian Xu, Lin Liu","doi":"10.1007/s00210-025-03998-z","DOIUrl":"https://doi.org/10.1007/s00210-025-03998-z","url":null,"abstract":"<p><p>Oxysterol binding protein-related protein 10 (OSBPL10) is a crucial sterol transporter that plays a significant role in regulating metabolic homeostasis. Previous studies have indicated that OSBPL10 promotes the development of several tumors. However, an integrative bioinformatics and immune infiltration analysis of OSBPL10 across various cancers has yet to be conducted. In this study, we comprehensively analyzed the expression patterns, prognostic value, genetic variations, protein modifications, immune infiltration characteristics, and biological functions of OSBPL10 in 33 human cancers using bioinformatics methods and publicly available databases, including TCGA, GEPIA2, GTEx, UCSC, UALCAN, HPA and TISCH2.0. The function of OSBPL10 and its associated mechanisms were confirmed in the pancreatic cancer cell lines Panc-1 and Mia PaCa-2. Our results revealed that OSBPL10 mRNA expression was significantly upregulated in 12 types of tumor tissues and downregulated in 3 cancers, which was notably associated with poor prognosis, pathological stage, and subtype in 10 tumors. Additionally, the level of promoter methylation exhibited a significant negative correlation with OSBPL10 mRNA expression. OSBPL10 expression was found to be dramatically associated with the levels of chemokines, chemokine receptors, immune checkpoints, and immune cell infiltration across various tumors by activating cancer pathways related to the extracellular matrix (ECM) and TSC/mTOR while downregulating tumor cell stemness. Furthermore, elevated OSBPL10 expression was negatively correlated with most drug sensitivities. In vitro experiments showed that OSBPL10 promoted the proliferation and migration of pancreatic cancer cells through the VEGF/AKT signaling pathway. In conclusion, our pan-cancer analysis suggests that OSBPL10 may serve as a critical biomarker for improving prognosis through OSBPL10-targeted therapies, immunotherapies, and chemotherapeutic combinations in cancer patients.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616279","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":"Role of human microbiota in facilitating the metastatic journey of cancer cells.","authors":"Himisa Shah, Princy Patel, Abhay Nath, Umang Shah, Ruma Sarkar","doi":"10.1007/s00210-025-03957-8","DOIUrl":"https://doi.org/10.1007/s00210-025-03957-8","url":null,"abstract":"<p><p>Cancer continues to be the leading cause of mortality worldwide, with metastasis being the primary contributor to cancer-related deaths. Despite significant advancements in cancer therapies, metastasis remains a major challenge in effective cancer management. Metastasis, the process by which cancer cells spread from the primary tumor to distant organs, is a complex phenomenon influenced by multiple factors, including the human microbiota. The human body encompasses various microorganisms, comprising bacteria, viruses, fungi, and protozoa, collectively known as microbiota. In fact, the microbiota is more abundant than human cells, and its disruption, leading to an imbalance in host-microbiota interactions (dysbiosis), has been linked to various diseases, including cancer. Among all microbiota, bacteria are one of the key contributors to cancer progression. Bacteria and bacteria-derived components such as secondary metabolites, QSPs, and toxins play a pivotal role in the metastatic progression of cancers. This review explores the intricate relationship between the human microbiota and cancer progression, focusing on different bacterial species which have been implicated in tumorigenesis, immune evasion, and metastasis. The present review explores the role of the human microbiome, specifically of bacteria in promoting metastasis in different types of cancers, demonstrating its ability to impact both the spread of tumors and their underlying mechanisms. This review also highlights the therapeutic potential and challenges of microbiome-based interventions in combating metastatic cancers. By addressing these challenges and by integrating microbiome-targeted strategies into clinical cancer treatment could represent a transformative approach in the fight against metastasis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616280","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":"Harnessing bee venom for inflammatory diseases management: from traditional medicine to nanotechnology.","authors":"Vandna Bhardwaj, Naresh Thakur, Priyanka Kumari","doi":"10.1007/s00210-025-03991-6","DOIUrl":"https://doi.org/10.1007/s00210-025-03991-6","url":null,"abstract":"<p><p>This review investigates the anti-inflammatory potential of bee venom, a natural compound comprising peptides, enzymes, biogenic amines other bioactive amines, and other bioactive components. It aims to elucidate how bee venom mitigates inflammatory responses caused by tissue injury, infections, and trauma. This study also explores the advancements in nanotechnology to enhance bee venom's therapeutic effects. A systematic review of studies from Google Scholar and PubMed, up to 2025, was conducted. Both in vitro and in vivo research focusing on bee venom's effects on proinflammatory mediators were analyzed. Specific attention was given to its molecular mechanisms, therapeutic impact on inflammatory conditions, and the role of nanotechnology in improving drug delivery and stability. Bee venom and its components, including melittin, apamin, and phospholipase A2 demonstrate robust anti-inflammatory properties by inhibiting key proinflammatory mediators. These effects have been observed in the treatment of chronic inflammatory conditions such as rheumatoid arthritis and skin disorders. Studies show bee venom's capacity to reduce excessive inflammatory responses effectively. Moreover, incorporating nanotechnology significantly enhances its therapeutic benefits by improving delivery, stability, and bioavailability, paving the way for advanced applications. Bee venom offers a natural, powerful approach to combating the inflammation and related chromic disorders. Its ability to regulate inflammatory pathways is promising for therapeutic use. The integration of nanotechnology further amplifies its potential, providing innovative solutions for efficient and targeted treatments. This study also highlights the need for more clinical trials to establish bee venom as a mainstream therapeutic agent in modern medicine.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616273","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":"Erbium oxide nanoparticles induce potent cell death, genomic instability and ROS-mitochondrial dysfunction-mediated apoptosis in U937 lymphoma cells.","authors":"Hanan R H Mohamed, Yusuf Ahmed Elberry, Hagar Magdy, Maryam Ismail, Maivel Michael, Nourhan Eltayeb, Gehan Safwat","doi":"10.1007/s00210-025-03962-x","DOIUrl":"https://doi.org/10.1007/s00210-025-03962-x","url":null,"abstract":"<p><p>Erbium oxide nanoparticles (Er₂O₃-NPs) have attracted significant attention for their unique physicochemical properties, including high surface area, biocompatibility, and stability. However, the impact of Er₂O₃-NPs on lymphoma cells (LCs) has not been explored, making this an innovative avenue for exploration. Therefore, the current study aimed to explore the influence of Er₂O₃-NPs on cell viability, genomic and mitochondrial DNA integrity, reactive oxygen species (ROS) generation and apoptosis induction in human U937 LCs. Er₂O₃-NPs were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The effect of Er₂O₃-NPs on cell viability and genomic DNA integrity was estimated after 48 h using the WST-1 cytotoxicity and alkaline Comet assays, respectively. The generation level of reactive oxygen species (ROS) and mitochondrial membrane potential were also analyzed. Flow Cytometry was used to assess apoptosis induction and quantitative RT-PCR was conducted to measure the apoptotic (p53), anti-apoptotic (Bcl2), and mitochondrial (ND3) gene expression. Our results demonstrated the purity and well distribution of Er₂O₃-NPs and revealed that Er₂O₃-NPs induce strong cytotoxicity on U937 cells, as evidenced by a concentration-dependent reduction in cell viability with an IC50 value of 3.20 µg/ml. Exposure of U937 LCs to the IC50 concentration (3.20 µg/ml) of Er₂O₃-NPs promoted excessive ROS generation, leading to dramatic damage to genomic DNA and mitochondrial membrane potential, as well as marked dysregulation of apoptotic (p53), anti-apoptotic (Bcl2) and mitochondrial ND3 gene expression. This cascade of events triggered both apoptosis and necrosis in Er₂O₃-NPs-treated U937 LCs. In conclusion, these findings highlight the strong in vitro cytotoxic potential of Er₂O₃-NPs against highly aggressive U937 LCs, mediated by excessive ROS production, which leads to severe genomic DNA and mitochondrial membrane damage, as well as profound alterations in apoptotic, anti-apoptotic and mitochondrial gene expression. Future research is needed to further investigate the potential use of Er₂O₃-NPs in treating lymphoma and to optimize their therapeutic efficacy.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616269","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}