Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Network Pharmacology and Molecular Docking Reveals Mechanism of Camphor on Liver Toxicity in Zebrafish","authors":"Man Wei,&nbsp;Leihui Xie,&nbsp;Jie Gan,&nbsp;Zhongshang Xia,&nbsp;Zhengcai Du","doi":"10.1111/bcpt.70222","DOIUrl":"10.1111/bcpt.70222","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the hepatotoxicity of camphor on zebrafish and its mechanism of toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We calculated concentration-response curves for zebrafish larvae treated with camphor at 72-h postexposure (hpe) and observed its toxic effects on liver. Employing network pharmacology and molecular pairs to predict key targets of camphor-induced hepatotoxicity, these critical targets were subsequently validated via qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study indicates that following 72 hpe to camphor, the LC50 and LC10 values for zebrafish larvae were 336 and 300 μg/mL, respectively. Concentrations of 300- and 150-μg/mL camphor significantly reduced liver fluorescence intensity and markedly elevated ALT and AST levels in zebrafish. At 300 μg/mL, pathological alterations in liver tissue were observed, including vacuolation, disordered hepatocyte arrangement and loosening of tissue structure, indicating potential hepatic damage. Integrative analysis via network pharmacology, molecular docking and qPCR revealed that camphor induces hepatotoxicity through multiple targets and pathways, either directly or indirectly. Key targets included GSR, GCLC and NQO1, while major involved pathways encompassed drug metabolism—other enzymes, chemical carcinogenesis—receptor activation, biosynthesis of cofactors and glutathione metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study has identified potential hepatotoxicity of camphor in zebrafish larvae, with its toxic mechanism involving multiple targets and pathways. The primary targets are likely GSR, GCLC and NQO1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643766","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":"In Vitro Antitrypanosomal and Antibacterial Activity of Aqueous, Hydroethanolic and Ethanolic Extracts of Rumex obtusifolius L. Leaf and Root","authors":"Gabriela K. Borges,&nbsp;Gabriella B. Das Neves,&nbsp;Letícia Reichardt,&nbsp;Ubirajara Maciel da Costa,&nbsp;Luiz C. Miletti,&nbsp;Amanda L. Bastos-Pereira","doi":"10.1111/bcpt.70230","DOIUrl":"10.1111/bcpt.70230","url":null,"abstract":"<p>Plant extracts are an important raw material for the development of new drugs. <i>Rumex obtusifolius</i> L., popularly known as ‘bitter dock’, has significant pharmacological properties. This study evaluated the in vitro antitrypanosomal activity of aqueous, hydroethanolic and ethanolic extracts from the leaf and roots of <i>R. obtusifolius</i> L. against <i>Trypanosoma evansi</i>, as well as their antibacterial activity against <i>Escherichia coli</i> and <i>Streptococcus aureus</i>. Antitrypanosomal assays were performed using extract concentrations of 0.5%, 1% and 2% and analysed by flow cytometry (necrosis). The antimicrobial activity was assessed at 1–100 mg/mL. Cytotoxicity was evaluated in mammalian cells for extracts active against <i>T. evansi</i>. The hydroethanolic and ethanolic leaf extracts exhibited significant anti-<i>T. evansi</i> activity, inducing necrosis rates of 64.6% and 63.7%, respectively. Besides, treatment with the ethanolic leaf extract (2%) of <i>R. obtusifolius</i> reduced cell viability to 14.3% after 24 h, whereas the hydroethanolic extract (2%) exhibited lower cytotoxicity, with cell viability remaining at approximately 65%–70%. None of the extracts exhibited antibacterial activity. In addition, our findings demonstrate a previously unreported pharmacological property of <i>R. obtusifolius</i>: the antitrypanosomal activity of its hydroethanolic and ethanolic extracts against <i>T. evansi</i>. Nevertheless, further studies are required to elucidate the mechanisms of action and to confirm a possible in vivo antitrypanosomal efficacy of these extracts.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632217","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":"Continuing the Progress in Deprescribing: Learnings From the Second International Conference on Deprescribing","authors":"Carina Lundby,&nbsp;Wade Thompson,&nbsp;Jean-Pascal Fournier","doi":"10.1111/bcpt.70231","DOIUrl":"10.1111/bcpt.70231","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618231","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":"Tailoring an Implementation Strategy for Deprescribing as Part of a Comprehensive Geriatric Assessment (dCGA) in Long-Term Care Facilities: A Roundtable Discussion","authors":"Dora Belec,&nbsp;Kieran Dalton,&nbsp;Clara H. Heinrich,&nbsp;Maja Ortner Hadžiabdić,&nbsp;Maria D. Donovan","doi":"10.1111/bcpt.70212","DOIUrl":"10.1111/bcpt.70212","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Comprehensive geriatric assessments (CGAs), with deprescribing as an integral component, improve outcomes for older adults in long-term care facilities (LTCFs). However, they remain underutilised in Croatia, partly due to systemic and cultural barriers, including limited recognition of pharmacists' roles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To tailor an existing deprescribing implementation strategy to support the introduction of deprescribing as part of a CGA (dCGA) in Croatian LTCFs, focusing on healthcare professional (HCP) behaviour change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A roundtable was held with Croatian HCPs—general practitioners, pharmacists and a nurse—experienced in LTCF care. Participants first ranked barriers and enablers to dCGA, then engaged in a structured discussion to explore tailored strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Key barriers included limited resources, fragmented data and restrictive policies. Enablers included multidisciplinary collaboration and education. A three-phase strategy (pre-, during, post-MDT) was developed, assigning the head nurse as dCGA lead and positioning pharmacists as deprescribing experts and trainers. Proposed mechanisms targeted priority barriers using Behaviour Change Techniques such as restructuring the social environment, goal setting and feedback loops.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study co-developed a feasible, context-specific strategy to integrate deprescribing into CGA in Croatian LTCFs. Future steps include pilot testing and evaluation in diverse LTCF settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618358","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":"Understanding Medication Errors Through Patient Complaints in a Danish University Hospital","authors":"Olga Tchijevitch,&nbsp;Søren Birkeland,&nbsp;Lars Morsø,&nbsp;Søren Bie Bogh","doi":"10.1111/bcpt.70233","DOIUrl":"10.1111/bcpt.70233","url":null,"abstract":"<p>Patient complaints are an important source of data, as they may help illuminate medication safety issues from the patient's perspective. We aimed to identify and describe medication errors (MEs) reported in patient complaints and compare them with MEs from safety incident reports. This descriptive hospital-based study (1) compared patient complaints with and without MEs using the Health Complaint Analysis Tool (HCAT) and (2) analysed MEs identified in both patient complaints and incident reports using the standard taxonomy of the reporting system. Of 6301 complaints, 310 (4.9%) were related to MEs. Compared with other complaints, ME-related complaints were more often submitted by family members (ratio 1.6), directed towards nursing staff (ratio 2.5), involved ward-based events (ratio 4.3) and occurred during discharge or transfer (ratio 2.9). Following selection and additional deduplication procedures, 202 MEs were identified in patient complaints. Compared with 8364 MEs from safety incident reports, patient complaints revealed higher proportions of antiepileptic and antipsychotic medication (ratio: 1.9), prescribing errors (ratio: 1.5), wrong medicine errors (ratio: 1.6) and errors with severe or fatal outcomes (ratio: 14.6). Patient complaints may uncover unique MEs not captured by traditional reporting systems. They may serve as a valuable complement to safety incident reports.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618292","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":"Repurposing Hetrombopag for Multiple Myeloma by Targeting PNPO: A Celastrol-Inspired Approach","authors":"Tianyi Yu,&nbsp;Cheng Wang,&nbsp;Jingru Xie,&nbsp;Yongxin Wei,&nbsp;Hongwei Cui,&nbsp;Huaxia Zhang,&nbsp;Fan Zhou,&nbsp;Zhendong Deng,&nbsp;Ye Yang,&nbsp;Chunyan Gu","doi":"10.1111/bcpt.70227","DOIUrl":"10.1111/bcpt.70227","url":null,"abstract":"<p>Multiple myeloma (MM) is a malignancy of plasma cells whose excessive immunoglobulin production elevates reactive oxygen species (ROS), promoting pathogenesis. Active compounds from Traditional Chinese Medicine, such as celastrol, can exert antitumour effects by further increasing ROS levels to toxic levels, thereby inducing apoptosis. Our previous study has demonstrated that pyridoxine-5′-phosphate oxidase (PNPO) is the specific target of celastrol. In this study, we discovered that PNPO, a key enzyme involved in vitamin B6 coenzyme metabolism, is highly expressed in various cancers, including MM. Increased PNPO levels correlated with MM disease progression, promoting cell proliferation and inducing osteoclast differentiation via exosomes. Concurrently, through a structure-based virtual screening workflow targeting critical PNPO residues (R95 and K117), we identified Hetrombopag as a potential PNPO inhibitor. Hetrombopag simultaneously inhibited MM cell proliferation and osteoclast differentiation. Preliminary data from clinical trials also supported the idea that hetrombopag treatment can prolong survival in MM patients. Our research highlights the significant role of PNPO in MM progression and suggests hetrombopag as a promising therapeutic option for MM treatment.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580532","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":"Impact of Tacrolimus Intra-Patient Variability on Toxicity Development Among Lung Transplant Recipients","authors":"Rita Nogueiras-Álvarez,&nbsp;Víctor Manuel Mora-Cuesta,&nbsp;José Manuel Cifrián-Martínez,&nbsp;María del Mar García-Saiz","doi":"10.1111/bcpt.70229","DOIUrl":"10.1111/bcpt.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>Immunosuppressive treatment helps to reduce the risk of rejection after transplantation. However, it is important to be aware of the potential toxicities that can develop after this therapy initiation. Tacrolimus is currently the calcineurin inhibitor of choice in the post-transplantation immunosuppressive therapy, and its intra-patient variability (Tac-IPV) has been proposed in recent years as a useful biomarker in post-transplant outcomes. We performed an observational retrospective study in 195 lung transplant recipients to determine the potential impact of Tac-IPV as a biomarker in the development of cardiovascular toxicities and renal impairment in the post-transplantation evolution. Different Tac-IPV calculation measurements were shown to be statistically associated with the development of arterial hypertension <i>de novo</i> in the univariate analysis: the standard deviation (<i>p</i> = 0.016 for tacrolimus C_min values; <i>p</i> = 0.022 for tacrolimus dose-adjusted values); the coefficient of variation (<i>p</i> = 0.021 for C_min; <i>p</i> = 0.031 for dose-adjusted values); and the mean absolute deviation (MAD) (<i>p</i> = 0.043 for C_min; <i>p</i> = 0.033 for dose-adjusted values). Those patients with a MAD ≥ 16.47% had a higher risk of renal impairment (<i>p</i> = 0.045). In our study, different Tac-IPV measures were associated with arterial hypertension in lung transplantation follow-up. Patients with a high Tac-IPV, using the MAD as a measurement, showed a higher risk for renal impairment. No other statistically significant associations were found for the other studied events.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509399","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":"Natural Compounds From Traditional Chinese Medicine Against Doxorubicin-Induced Cardiotoxicity: Biological Mechanisms and Therapeutic Potential","authors":"Min Li,&nbsp;Ruijin Qiu,&nbsp;Shuai Wang,&nbsp;Qianqian Xu,&nbsp;Kunze Li,&nbsp;Hong Chen,&nbsp;Chen Zhao,&nbsp;Huichan Yuan,&nbsp;Jianquan Chen,&nbsp;Huiyuan Sun,&nbsp;Hongcai Shang","doi":"10.1111/bcpt.70228","DOIUrl":"10.1111/bcpt.70228","url":null,"abstract":"<p>The clinical application of doxorubicin (DOX) is severely restricted by its dose-dependent cardiotoxicity. This study aimed to investigate the protective mechanisms of traditional Chinese medicine–derived natural compounds (TCM-NCs) against DOX-induced cardiotoxicity. A systematic analysis was performed on 104 preclinical studies (encompassing in vivo and in vitro models) retrieved from PubMed, Web of Science and Embase, summarising the cardioprotective effects and mechanisms of 65 TCM-NCs. These compounds exert multitarget protective effects by modulating six core pathways: oxidative stress/ferroptosis, apoptosis, inflammation/pyroptosis, mitochondrial homeostasis, autophagy and endoplasmic reticulum stress. Target validation further identified Nrf2, Sirt1, mTOR and AMPK as potential central hub nodes underlying their protective actions. These findings offer a theoretical foundation and promising drug candidates for the prevention of chemotherapy-related cardiac injury, with future research directions focusing on clinical translation and druggability optimisation.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509414","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":"Community Pharmacists' Role in Antidepressant Discontinuation: A Survey of Barriers and Facilitators","authors":"Ketura Verheye,&nbsp;Ine Vangrieken,&nbsp;Kato De Pril,&nbsp;Els Mehuys,&nbsp;Koen Boussery,&nbsp;Thierry Christiaens,&nbsp;Ellen Van Leeuwen","doi":"10.1111/bcpt.70226","DOIUrl":"10.1111/bcpt.70226","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Long-term antidepressant use is widespread in high-income countries. While general practitioners (GPs) are central in reviewing and discontinuing antidepressants, community pharmacists (CP) may support this process. However, barriers and facilitators to CP involvement remain underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aims to explore CPs' perceptions of long-term antidepressant discontinuation and their roles in the antidepressants discontinuation process and to identify key barriers and facilitators for engaging in this process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional online survey was conducted among Belgian CPs. Items assessing perceived roles and barriers/facilitators were rated on Likert scales and categorized by mean scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 190 CPs completed the survey. Pharmacists identified their main responsibilities as informing patients, compounding tapering formulations and contacting physicians during tapering when problems arise. The only barrier classified as major was resistance from GPs to antidepressant discontinuation. Eleven major facilitators were identified, including patient-initiated requests, good GP collaboration, strong trust relationships with patients and access to guidelines, information and education on discontinuation of antidepressants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CPs currently tend to adopt a largely reactive approach towards discontinuing long-term antidepressants. Interventions aiming to promote more proactive engagement may focus on clarifying roles and responsibilities, strengthening collaboration with GPs and supporting pharmacists through education, practical resources and communication training.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484331","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":"Nephroprotective Effects of Vanillic Acid on Bortezomib-Induced Renal Injury: Role of Oxidative Stress, Mitochondrial Dysfunction, Apoptosis and miR-204/Nephrin/Podocin/CD2AP Axis","authors":"Medine Akkan Öz,&nbsp;Hasan Şimşek,&nbsp;Selçuk Özdemir,&nbsp;Sefa Küçükler,&nbsp;Özge Kandemir,&nbsp;Hüseyin Mutlu,&nbsp;Ramiz Yazıcı,&nbsp;Fatih Mehmet Kandemir","doi":"10.1111/bcpt.70223","DOIUrl":"10.1111/bcpt.70223","url":null,"abstract":"<div>\u0000 \u0000 <p>Bortezomib (BTZ) is clinically important in the nephrological field because of its increasing use in plasma cell disorders and antibody-mediated kidney diseases, where it can both exert therapeutic benefits and, paradoxically, cause significant renal toxicity. This study investigated the protective effects of vanillic acid (VA) against BTZ-induced acute kidney injury using biochemical and molecular approaches. BTZ administration elevated serum creatinine, blood urea nitrogen, KIM-1 and NGAL, while co-treatment with VA partially normalized these markers. BTZ increased apoptotic markers (BAX, PUMA and TRAIL) and inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-10), which were attenuated by VA. Oxidative stress–related genes NQO1, NOX4 and XO were upregulated, and GPX4 was downregulated by BTZ; VA restored these expressions. BTZ disrupted mitochondrial dynamics and energy metabolism (MFN2, CPT1A and OxPhos decreased; FIS1 increased), with VA ameliorating these changes. Energy imbalance induced by BTZ, reflected by reduced ATP and increased LDH and TAG, was also mitigated by VA. Podocyte proteins nephrin, podocin and CD2AP were reduced, accompanied by increased LAMP1 and decreased miR-204-5p; VA partially restored these levels. Overall, VA protected against BTZ-induced kidney injury via antioxidant, anti-inflammatory, antiapoptotic and mitochondrial mechanisms, potentially involving the miR-204-5p–nephrin axis.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490358","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}