BMC Pharmacology & Toxicology最新文献

{"title":"Correction to: In vitro comparative quality evaluation of different brands of metformin hydrochloride tablets available in Mekelle City, Tigray Regional State, Ethiopia.","authors":"Brhane Gebrehiwot Welegebrial, Zenawi Gezae, Samrawit Kidanemariam Gebrekidan, Gebru Gebremeskel Gebrerufael, Haylay Araya Gebregzabiher, Abrahaley Mulu Kidane, Gebretekle Gebremichael Hailesilase","doi":"10.1186/s40360-026-01202-3","DOIUrl":"10.1186/s40360-026-01202-3","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic attenuation by L-carnitine of trastuzumab-induced downregulation of adenosine monophosphate -activated protein kinase signal in cardiac H9c2 cells.","authors":"Yasmin M Attia, Abdel-Moneim M Osman, Emad Shash, May Elgazzar, Marwa Sharaky, Fawaz E Alanazi, Mohamed M Sayed-Ahmed, Riham M Karkeet","doi":"10.1186/s40360-026-01235-8","DOIUrl":"10.1186/s40360-026-01235-8","url":null,"abstract":"<p><strong>Background: </strong>Clinical usefulness of trastuzumab (TZ) is restrained owing to its cardiotoxic effect. This investigation was initiated to evaluate the potential protective impact of carnitine (CARN) against TZ-related cardiac influence; and to uncover the underlining mechanism.</p><p><strong>Methods: </strong>Cytotoxic effect of TZ, CARN and their combination was assessed in cardiac H9c2 cells. Carnitine pamlitoyltransferase-1B (CPT1B) and adenosine monophosphate activated protein kinase-α2 (AMPK-α2) expression were investigated using quantitative real-time Polymerase Chain Reaction (RT-PCR). Troponin I, creatine kinase-MB (CK-MB), Adenosine triphosphate (ATP), malonyl-CoA, acetyl-CoA carboxylase-2 (ACC2) and autophagy protein 5 (ATG-5) were investigated using Enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Challenging cardiac cell with TZ resulted in concentration-dependent decrease in cell viability with inhibitory concentration 50 (IC₅₀) of (1.21 uM). Combining TZ's IC₅₀ and CARN (5 mM) resulted in the most profound drop of cardiac cellular toxicity. Trastuzumab elevated Troponin I, CK-MB, ACC-2 and Malonyl-CoA, while CARN counteracted this elevation. TZ decreased mRNA expression of AMPK-α2 and CPT1B; as well as ATP and ATG-5 levels, but combination of TZ and CARN counteracted this reduction.</p><p><strong>Conclusions: </strong>TZ disorders AMPK-α2 downstream signaling with the consequent decrease of ATP production and disturbs autophagy. Carnitine tempers TZ-related cardiotoxicity and acts as guard against TZ-related cardiac impact. The current findings are preliminary and highlight the need for additional studies to answer this current research question.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and bioequivalence evaluation of teneligliptin hydrobromide tablets following single-dose administration in healthy Chinese volunteers under fasting and fed conditions.","authors":"Zhaofeng Guan, Mingqi Chen, Biying Wei, Jianfen Su, Dongmei Tan, Jiefeng Ke, Guoping Huang","doi":"10.1186/s40360-026-01234-9","DOIUrl":"https://doi.org/10.1186/s40360-026-01234-9","url":null,"abstract":"<p><strong>Background: </strong>By inhibiting dipeptidyl peptidase-4 (DPP-4), teneligliptin provides a therapeutic option for type 2 diabetes mellitus (T2DM) that is widely used in Asia. A generic product could lessen treatment costs, provided that its systemic availability is equivalent to that of the branded formulation. Such comparative information remains scarce for Chinese recipients of teneligliptin hydrobromide. We therefore investigated a new generic tablet as the test product and Tenelia^® as the reference product in fasted and fed settings.</p><p><strong>Methods: </strong>A total of 52 healthy Chinese adults participated in a randomized, open-label crossover investigation involving one dose, two sequences, and two periods; 26 participants were assigned to each sequence. The test and reference products were each administered at 40 mg in the fasting and fed studies, and administrations were 7 days apart. A validated LC-MS/MS assay yielded plasma teneligliptin concentrations. After logarithmic transformation, AUC_0-t, AUC_0-∞, and C_max were subjected to analysis of variance (ANOVA). Equivalence required the 90% confidence interval (CI) of each test/reference geometric mean ratio (GMR) to fall completely between 80% and 125%. CTCAE v5.0 was used to grade adverse events (AEs).</p><p><strong>Results: </strong>In each dietary setting, the two products produced similar teneligliptin exposure. For AUC_0-t, AUC_0-∞, and C_max, every test/reference GMR had a 90% CI between the predefined boundaries of 80% and 125%. Serious adverse events (SAEs) did not occur.</p><p><strong>Conclusion: </strong>Whether administered in the fasting or fed state, the generic tablet met the regulatory requirements for bioequivalence with Tenelia^®. The pharmacokinetic comparison consequently supports the generic product as an equivalent alternative.</p><p><strong>Trial registration: </strong>The study was registered retrospectively in the Chinese Clinical Trial Registry (ChiCTR2500112749; November 19, 2025). Ethical approval was obtained from the Ethics Committee of The Affiliated Panyu Central Hospital, Guangzhou Medical University (PYZXYYEC [2025-013 (YW)]-01).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLGA-loaded puerarin attenuates arsenic-induced liver injury through modulation of ferroptosis, oxidative stress, inflammation, and apoptotic signaling.","authors":"Shaza A Alyamani, Badriah A Hifni, Nasser S Alqahtani, Ekramy M Elmorsy, Ayat B Al-Ghafari, Huda A Al Doghaither, Wajid Ali Chatha, Gehad E Elshopakey","doi":"10.1186/s40360-026-01221-0","DOIUrl":"10.1186/s40360-026-01221-0","url":null,"abstract":"<p><strong>Background: </strong>Arsenic (AR) is an environmental and mining occupational toxicant with reported hepatotoxic effects. Ferroptosis has recently emerged as a critical mechanism involved in arsenic-induced hepatotoxicity. This study investigated the hepatoprotective effects of puerarin (PU) and its PLGA-loaded nanoparticle formulation (PU-PLGA) against arsenic-induced liver injury in rats, with particular emphasis on ferroptosis pathways modulation.</p><p><strong>Methods: </strong>Sixty adult male Sprague-Dawley rats were randomly assigned into six groups: control, PU, PU-PLGA, arsenic (AR), AR + PU, and AR + PU-PLGA. Subacute hepatotoxicity was induced by oral administration of arsenic (10 mg/kg) for 14 days. Oxidative stress, ferroptosis-related biomarkers, inflammatory mediators, apoptotic markers, fibrotic indicators, DNA damage, histopathological alterations, and ultrastructural changes were evaluated.</p><p><strong>Results: </strong>Arsenic exposure induced marked hepatic injury characterized by Fe²⁺ accumulation, increased lipid peroxidation markers (MDA and 4-HNE), upregulation of ACSL4, and suppression of GPX4 and SLC7A11, indicating enhanced ferroptotic activity. These alterations were accompanied by oxidative stress, inflammatory activation (NF-κB, TNF-α, IL-6, IL-1β, and COX-2), apoptotic signaling (Bax and caspase-3), DNA damage (8-OHdG and DNA fragmentation), and fibrotic responses (TGF-β and collagen I). Treatment with PU and PU-PLGA significantly attenuated arsenic-induced hepatic injury by reducing iron accumulation and lipid peroxidation, restoring GPX4 and SLC7A11 expression, and suppressing ACSL4 upregulation. Notably, PU-PLGA demonstrated greater efficacy than free PU in modulating ferroptosis-related biomarkers, restoring antioxidant and survival signaling (Nrf2, p-AKT, and Bcl-2), and improving hepatic histopathological and ultrastructural integrity.</p><p><strong>Conclusion: </strong>P PU-PLGA nanoparticles exerted potent hepatoprotective effects against arsenic-induced liver injury, associated with modulation of ferroptosis-related pathways, oxidative stress, inflammatory responses, apoptosis-associated signaling, and profibrotic alterations. These findings highlight PU-PLGA as a promising nanotherapeutic strategy for arsenic-associated hepatotoxicity, although further mechanistic and translational validation is warranted.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of serious adverse effects of antidiabetic drugs and complications associated with type II diabetes mellitus.","authors":"Hadeer Ehab Barakat, Mohamed Adel Ibrahim, Ahmed Essam AbouWarda, Mariym Youssif Abdelmoneam, Mohamed F Sallam, Salwa Selim Abougalambou","doi":"10.1186/s40360-026-01211-2","DOIUrl":"10.1186/s40360-026-01211-2","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is a major global health problem for which a wide range of antidiabetic medications are available. Adverse effects of antidiabetic medications may negatively affect patients' health and treatment adherence. In Egypt, limited data are available regarding the adverse-effect profiles of antidiabetic agents.</p><p><strong>Aim: </strong>This study aimed to compare safety profiles, treatment-related adverse effects, and diabetes-related complications associated with commonly prescribed antidiabetic medications.</p><p><strong>Materials and methods: </strong>A multicenter, cross-sectional observational study was conducted across diabetes outpatient clinics in Egypt from February 2024 to May 2024. Adult patients with type 2 diabetes on antidiabetic regimens were enrolled. Data was collected through medical records and patient interviews, including demographics, clinical history, laboratory results, diabetes complications, and treatment-related adverse events. Univariate logistic regression analyses were performed to assess the associations between antidiabetic medications and diabetes-related complications and adverse outcomes. Unadjusted odds ratios (ORs) with 95% confidence intervals were reported. Statistical significance was set at p-value ≤ 0.05.</p><p><strong>Results: </strong>Several statistically significant associations were observed between the use of different antidiabetic medications and the prevalance of side effects and diabetes-related complications. Among 1,534 participants, insulin was associated with increased odds of cardiovascular, renal, and peripheral complications. Metformin, liraglutide, and empagliflozin were linked to gastrointestinal issues. Various mental disorders were notably associated with insulin. Empagliflozin and sitagliptin showed higher infection risks, while insulin and sulphonylureas were linked to some organ damage and retinopathy.</p><p><strong>Conclusion: </strong>Understanding the safety profiles of antidiabetic drugs is essential for optimizing treatment. The observed associations may help inform clinical decision-making and improve patient outcomes. However, they should be interpreted as associations rather than causal relationships and warrant further investigation in well-designed prospective studies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-informed AUC-guided dosing for parenteral vancomycin in critically ill patients: impact on target attainment and renal safety - a pre-post intervention study.","authors":"Laura Gundlach, Mareike Kunkel, Oliver Scherf-Clavel, Güzin Surat","doi":"10.1186/s40360-026-01224-x","DOIUrl":"10.1186/s40360-026-01224-x","url":null,"abstract":"<p><strong>Background: </strong>Parenteral vancomycin is essential for the treatment of certain gram-positive infections but is associated with acute kidney injury (AKI). The 2020 IDSA guideline recommends AUC₂₄-based dosing for MRSA to increase treatment safety. Due to the low MRSA prevalence at the University Hospital of Würzburg (UKW), this study investigated the impact of model-informed precision dosing (MIPD) of vancomycin on AKI incidence and target attainment in MRSA and non-MRSA infections.</p><p><strong>Methods: </strong>This pre-post intervention study compared a retrospective group (January 1, 2019 - June 30, 2021) with a prospective group (October 17, 2022 - December 31, 2023), including critically ill patients from intensive and intermediate care units. The prospective group received AUC₂₄-based MIPD using Bayesian pharmacometric modeling performed by a clinical pharmacist. The primary outcome was the incidence of AKI. Secondary outcomes included vancomycin therapeutic target attainment and the proportions of therapies within, below, and above the therapeutic range.</p><p><strong>Results: </strong>AKI occurred in 27.8% of the retrospective group and 14.0% of the prospective group (p = 0.04). The AUC-based group achieved therapeutic targets more frequently (70.2% vs. 55.1%, p = 0.049) and had fewer supratherapeutic levels (8.8% vs. 24.5%, p = 0.01).</p><p><strong>Conclusions: </strong>AUC₂₄-based MIPD for vancomycin improved therapeutic target attainment and was associated with a lower observed incidence of AKI. These findings support further evaluation of AUC-guided dosing for both MRSA and non-MRSA infections.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multinational pharmacovigilance assessment of drug-associated esophageal ulceration and perforation: evidence from FAERS, JADER, and Canada Vigilance.","authors":"Lihua Zhang, Xinchi Luan, Caiqi Liu, Xiaofei Xin, Xiaolei Zhang, Shufen Zhao, Wensheng Qiu","doi":"10.1186/s40360-026-01223-y","DOIUrl":"10.1186/s40360-026-01223-y","url":null,"abstract":"<p><strong>Background: </strong>Drug-associated esophageal ulceration and perforation are uncommon but clinically serious adverse events. This study characterized post-marketing reporting patterns for these events across three spontaneous reporting systems.</p><p><strong>Methods: </strong>Reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), Japanese Adverse Drug Event Report database (JADER), and Canada Vigilance from 2004 to 2025 were analyzed using predefined Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. Disproportionality was assessed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). In FAERS, least absolute shrinkage and selection operator (LASSO) regression followed by multivariable logistic regression was used for exploratory signal prioritization. Reported time-to-onset was summarized for drug-report records with valid therapy start and event onset dates.</p><p><strong>Results: </strong>FAERS contained 8,061 reports meeting the prespecified composite case definition. Among the 50 most frequently reported FAERS primary-suspect drugs, the largest disproportionality estimates were observed for doxycycline (ROR 41.15, 95% confidence interval [CI] 36.47-46.43), alendronic acid (ROR 21.45, 95% CI 19.14-24.04), and clindamycin (ROR 18.59, 95% CI 15.40-22.44). JADER and Canada Vigilance showed descriptively overlapping but heterogeneous reporting patterns. Reported time-to-onset was heterogeneous, with both short and long recorded intervals.</p><p><strong>Conclusions: </strong>This multidatabase analysis identified prominent reporting signals for established pill-injury drugs and exploratory reporting patterns involving other drug categories. These findings are hypothesis-generating and should not be interpreted as estimates of incidence, comparative clinical risk, or causal effects.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the toxicological effects of synthetic musk ketone using the Caenorhabditis elegans model.","authors":"Jun-Tao Sun, Qi Zhao, Ying-Ying Ren, Tian-Yu Wang, Wen-Hua Qi","doi":"10.1186/s40360-026-01220-1","DOIUrl":"10.1186/s40360-026-01220-1","url":null,"abstract":"<p><strong>Background: </strong>Synthetic musk ketone (MK) is extensively used in perfumes, cosmetics, and detergents. Due to its high lipophilicity, persistence, and limited removal efficiency in wastewater treatment, MK has been detected in various environmental matrices and human tissues. However, the ecotoxicity of MK remains poorly characterized. This study aimed to systematically evaluate the toxicological effects of MK and elucidate its underlying mechanisms using Caenorhabditis elegans (C. elegans) as a model organism.</p><p><strong>Methods: </strong>Wild-type C. elegans (strain N2) were exposed to MK at concentrations ranging from 0.4 to 20 mg/L for 24 h. Physiological endpoints including body size, locomotor activity, lifespan, and brood size were assessed. Biochemical markers comprising reactive oxygen species (ROS) levels and lipofuscin accumulation were quantified. Acute heat-stress tolerance was evaluated to assess stress resistance. Transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) were employed to investigate molecular mechanisms. Differential gene expression analysis was performed using DESeq2, and functional enrichment analyses were conducted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.</p><p><strong>Results: </strong>MK exposure significantly and concentration-dependently reduced body length and width, locomotor activity (head thrash and body bend frequencies), brood size, and lifespan. Lipofuscin accumulation and intracellular ROS levels were markedly elevated. Acute heat-stress tolerance was significantly impaired. Transcriptomic analysis identified 159 differentially expressed genes (DEGs) at 2 mg/L MK (19 up-regulated, 140 down-regulated) and 136 DEGs at 20 mg/L MK (30 up-regulated, 106 down-regulated). Key DEGs included ugt-30 (detoxification), Y9C9A.16 (oxidation-reduction), msp-59 (spermatogenesis), and acdh-8 (lipid metabolism). GO enrichment revealed significant alterations in spermatogenesis, protein catabolism, and kinase activity. KEGG pathway analysis identified perturbations in sulfur metabolism, branched-chain amino acid metabolism, fatty acid metabolism, and apoptosis. Protein-protein interaction network analysis identified cyc-2.2 and acdh-8 as hub genes.</p><p><strong>Conclusions: </strong>MK exposure induces multi-faceted toxicity in C. elegans, including developmental impairment, neurotoxicity, reproductive toxicity, accelerated aging, and diminished stress resilience. These adverse outcomes are strongly associated with oxidative stress, germline impairment, and disrupted lipid metabolism, suggesting that these pathways play central roles in MK-induced toxicity. Our findings indicate that environmental exposure to MK may pose significant toxicological risks to living organisms and warrant further assessment of its ecological and health impacts.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin-loaded liposomal nanoparticles alleviate streptozotocin-induced diabetic hepatopathy associated with modulation of ferroptosis-related and inflammatory signaling.","authors":"Badriah A Hifni, Shaza A Alyamani, Nasser S Alqahtani, Ayat B Al-Ghafari, Huda A Al Doghaither, Ekramy M Elmorsy, Manal S Fawzy, Gehad E Elshopakey","doi":"10.1186/s40360-026-01213-0","DOIUrl":"10.1186/s40360-026-01213-0","url":null,"abstract":"<p><strong>Background: </strong>Diabetic hepatopathy is a major complication of type 2 diabetes mellitus characterized by metabolic dysregulation, oxidative stress, inflammation, and emerging evidence of ferroptosis-mediated liver injury. Icariin (IC), a bioactive flavonoid, exhibits hepatoprotective potential; however, its clinical applicability is limited by poor bioavailability. Liposomal nanoformulation represents a potential approach to modify IC delivery and enhance its pharmacological efficacy.</p><p><strong>Methods: </strong>Ninety rats were randomly assigned to six groups (n = 15/group): Control, IC, IC-LNPs, NA-STZ, NA-STZ + IC, and NA-STZ + IC-LNPs. Type 2 diabetes was induced by nicotinamide (120 mg/kg, i.p.) followed 15 min later by streptozotocin (60 mg/kg, i.p.). Five days after diabetes confirmation, diabetic treatment groups received IC or IC-LNPs at an IC-equivalent dose of 80 mg/kg/day, i.p., for eight consecutive weeks. Hepatic injury was assessed through biochemical parameters, oxidative stress markers, inflammatory cytokines, ferroptosis-related markers, and histopathological and ultrastructural analyses.</p><p><strong>Results: </strong>NA-STZ administration induced significant metabolic dysfunction, including hyperglycemia, insulin depletion, dyslipidemia, weight loss, and elevated hepatic enzyme levels. IC treatment significantly improved these parameters, while IC-LNPs produced a more pronounced protective effect. Diabetic induction was associated with reduced hepatic NRF2 and HO-1 levels, accompanied by reduced levels of GSH, SOD, CAT, and GPX, and increased oxidative stress markers (MDA and H₂O₂). IC-LNPs more effectively restored antioxidant defenses and redox homeostasis than free IC. Moreover, NA-STZ increased NF-κB and COX-2 expression and the inflammatory mediators TNF-α, IL-6, and IL-1β, which were markedly reduced by IC-LNP treatment. Importantly, diabetic hepatopathy was associated with alterations in ferroptosis-related markers, evidenced by iron accumulation (Fe²⁺), upregulation of ACSL4 and TFR1, and downregulation of GPX4 and SLC7A11. IC-LNPs significantly attenuated these alterations, consistent with modulation of ferroptosis-related processes. Histopathological and ultrastructural analyses confirmed severe hepatic damage in diabetic rats, whereas IC-LNPs markedly preserved hepatic architecture.</p><p><strong>Conclusion: </strong>IC-LNPs provided greater protection than free IC against NA-STZ-induced diabetic hepatopathy, associated with attenuation of oxidative stress and inflammation and modulation of NRF2/HO-1, NF-κB/COX-2, and ferroptosis-related markers. These findings support the potential of liposomal IC as a preclinical approach for diabetic liver injury; however, pharmacokinetic, biodistribution, safety, and further mechanistic studies are required before its therapeutic or translational potential can be established.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective role of aldehyde dehydrogenase 2 in retinal pigment epithelium cells with CoCl₂-induced hypoxic injury: an in-vitro study.","authors":"Sheng Zhang, Guanyu Chen, Lin Xiao, Jialing Dong, Yin Chao, Yuxin Xia, Pan Long, Weiming Yan","doi":"10.1186/s40360-026-01207-y","DOIUrl":"10.1186/s40360-026-01207-y","url":null,"abstract":"<p><strong>Background: </strong>Retinal pigment epithelial (RPE) cells are vulnerable to hypoxia-related and oxidative stress. Cobalt chloride (CoCl₂) is widely used as a chemical hypoxia mimetic; however, an appropriate concentration window for producing measurable RPE injury without the more extensive damage associated with higher concentrations remains incompletely defined. Aldehyde dehydrogenase 2 (ALDH2) contributes to reactive-aldehyde detoxification and cellular stress defense.</p><p><strong>Methods: </strong>ARPE-19 cells were exposed to 0, 10, 100, 500, 1000, or 2000 µM CoCl₂. Scratch-wound recovery and representative morphology were evaluated for up to 72 h, and relative CCK-8 metabolic activity was quantified at 24, 48, and 72 h. The 500 µM condition was selected for molecular and pharmacological experiments based on the integrated dose-response profile. Culture-supernatant 4-HNE and VEGF-A were measured by ELISA, whereas HIF-1α, ALDH2, and BAX were assessed by Western blotting. Alda-1 and Daidzin were used as an ALDH2 activator/chemical chaperone and an enzymatic inhibitory comparator, respectively.</p><p><strong>Results: </strong>CoCl₂ caused concentration- and time-associated impairment of scratch-wound recovery. Wound closure was largely preserved at 0-100 µM, whereas 500-2000 µM produced wound-closure failure. The CCK-8 profile showed that 500 µM retained a nonmaximal metabolic signal compared with the substantially greater late reductions observed at 1000 and 2000 µM. Thus, 500 µM represented the lowest tested concentration producing significant functional injury while avoiding the more extensive injury phenotype observed at higher concentrations. Under 500 µM CoCl₂, HIF-1α increased early, ALDH2 protein abundance decreased, and culture-supernatant 4-HNE and VEGF-A increased at the later time point. Alda-1 improved wound recovery and restored ALDH2 protein abundance, whereas Daidzin aggravated the functional injury phenotype and shifted extracellular stress-marker readouts in an unfavorable direction.</p><p><strong>Conclusions: </strong>CoCl₂ produced a concentration-resolved, hypoxia-related and aldehyde-associated RPE injury phenotype. Alda-1 improved wound recovery and increased ALDH2 protein abundance, whereas Daidzin aggravated the functional injury phenotype. These findings support ALDH2-associated aldehyde-detoxifying defense as a modulatory component of CoCl₂-induced RPE stress.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}