Journal of Biochemical and Molecular Toxicology最新文献

{"title":"2-Hydroxyethyl Methacrylate Increases MMP-1 and MMP-3 Production in Human Gingival Fibroblasts","authors":"Risa Okamoto,&nbsp;Yoshitaka Hosokawa,&nbsp;Ikuko Hosokawa,&nbsp;Ai Fukui,&nbsp;Natsuho Miyake,&nbsp;Kazumi Ozaki,&nbsp;Keiichi Hosaka","doi":"10.1002/jbt.71083","DOIUrl":"https://doi.org/10.1002/jbt.71083","url":null,"abstract":"<p>2-Hydroxyethyl methacrylate (HEMA), a monomer commonly used in dental resin materials, has been reported to leach from polymerized resins. However, its potential impact on periodontal tissues remains insufficiently understood. This study investigates the effects of HEMA on human gingival fibroblasts (HGFs), which constitute a major component of periodontal connective tissue. Specifically, we examined whether HEMA induces the production of pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), as well as matrix metalloproteinases (MMP)-1 and MMP-3, which are involved in collagen degradation. Furthermore, we analyzed the intracellular signaling pathways activated by HEMA exposure to elucidate the molecular mechanisms underlying these responses. Cytokine and MMP production were analyzed using the ELISA. In addition, activation of intracellular signaling pathways were examined by Western blot analysis. HEMA treatment did not induce IL-6 or IL-8 production, but significantly increased MMP-1 and MMP-3 levels in a concentration-dependent manner. In contrast, tissue inhibitor of metalloproteinases (TIMP)-1 production was suppressed by HEMA. Moreover, compared with 24-h exposure, 48-h exposure induced increases in MMP production and decreases in TIMP-1 production at lower concentrations of HEMA. Furthermore, HEMA enhanced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and protein kinase B (Akt). Inhibitor studies revealed that the p38 MAPK, extracellular signal-regulated kinase (ERK), JNK, and Akt signaling pathways are involved in the regulation of MMP-1 and MMP-3 production. These findings suggest that HEMA leaching from resin materials may contribute to periodontal tissue destruction by promoting MMP production in HGFs through activation of specific signaling pathways. Given the potential impact of HEMA on periodontal tissues, it is important to ensure complete polymerization of light-curable resin materials and thorough removal of excess resin cement. The use of HEMA-free materials may also be worth considering to minimize biological risks.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784594","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":"Downregulation of circ_0001112 Enhances Myocardial Infarction Through Regulation of miR-324-5p/CDK6 Axis","authors":"Aizhen Hu,&nbsp;Lina Zhang,&nbsp;Xingping Men","doi":"10.1002/jbt.70995","DOIUrl":"https://doi.org/10.1002/jbt.70995","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial infarction (MI) usually results in severe heart failure (HF), and patients suffer from the repercussions of MI, elucidation of the pathological basis of MI is crucial to optimize the prevention and treatment of MI. This study investigated the role of dysregulated circ_0001112 in MI. In our study, circ_0001112 was significantly upregulated in the MI model and by hypoxia treatment. Circ_0001112 overexpression inhibited hypoxia-induced cardiomyocyte apoptosis. Luciferase assay showed that circ_0001112 sponged miR-324-5p that regulated the expression of cyclin-dependent kinase 6 (<i>CDK6</i>). Ago2-miRNP immunoprecipitation further confirmed that the 3′-untranslated region (3'UTR) of <i>CDK6</i> was targeted by miR-324-5p. Either miR-324-5p overexpression or CDK6 knockdown prevented cardiomyocyte apoptosis induced by circ_0001112 overexpression. In conclusion, this study demonstrated that the downregulation of circ_0001112 promoted cardiomyocyte apoptosis by sponging miR-324-5p and upregulating CDK6 expression in MI.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Mesenchymal Stem Cells Rescue Tendon Injury by Regulating FTO-Mediated m6A Methylation of ELOB","authors":"Zhao-Rong Dai,&nbsp;Guo-Hua Luo,&nbsp;Yan-Qiu Xie","doi":"10.1002/jbt.71069","DOIUrl":"https://doi.org/10.1002/jbt.71069","url":null,"abstract":"<p>Bone marrow mesenchymal stem cells (BMSCs) prominent capacity for tissue repair and regenerative applications due to their multipotent differentiation potential and immunomodulatory activities. This study explores the function of BMSCs in tendon repair, with a particular focus on their regulatory effect on fat mass and obesity-associated protein (FTO)-mediated m6A methylation of Elongin B (ELOB). In this study, BMSCs were isolated from mice with experimental tendon injury and characterized by detecting the expression of surface biomarkers (CD90, CD44, CD29, CD34, CD45). The proliferation, migration, apoptosis, and intracellular reactive oxygen species (ROS) levels of tenocytes were assessed using CCK-8 assay, wound healing assay, and flow cytometry. RT-qPCR and Western blot analysis were applied to quantify gene and protein expression, respectively. Dual luciferase reporter assay and methylated RNA immunoprecipitation (MeRIP) were performed to verify the regulatory relationship between FTO and ELOB. Functional recovery of injured tendons in mice was evaluated via behavioral tests and hematoxylin and eosin (HE) histological staining. The results showed that BMSCs effectively facilitated tendon repair in the murine tendon injury model. The RNA demethylase FTO was markedly downregulated in injured tendon tissues, and its expression could be modulated by BMSCs. Mechanistically, BMSCs upregulated FTO to accelerate tenocyte proliferation and migration, and simultaneously suppress oxidative stress during tendon injury. FTO repressed ELOB expression through m6A modification. Functional assays further demonstrated that FTO improved tenocyte proliferation and migration, and alleviated oxidative stress by downregulating ELOB. In vivo assays validated that overexpression of FTO boosted tendon repair by reducing ELOB expression. In conclusion, BMSCs improve tendon repair by stimulating tenocyte proliferation and migration and alleviating oxidative stress. This protective mechanism is dependent on the regulation of FTO-mediated m6A methylation of ELOB.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784595","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":"miR-138-5p Inhibits Aortic Valve Interstitial by Targeting SLC39A14 and Activating Nrf2 Signaling","authors":"Fei Yan,&nbsp;Ying Zhao,&nbsp;Yuanyuan Wu,&nbsp;Dubiao Xian,&nbsp;Lei Shi,&nbsp;Yunheng Liang,&nbsp;Ning Wang,&nbsp;Ruiling He,&nbsp;Hongwang Cui,&nbsp;Zhihao Xie","doi":"10.1002/jbt.71034","DOIUrl":"https://doi.org/10.1002/jbt.71034","url":null,"abstract":"<p>This study explored the role of <i>miR-138-5p</i> in calcific aortic valve disease (CAVD), focusing on its regulation of osteogenic differentiation in human aortic valve interstitial cells (hAVICs) and underlying mechanisms. Aortic valve tissues from CAVD patients and controls were analyzed for <i>miR-138-5p</i> expression using qRT-PCR. hAVICs were cultured in osteogenic medium (OM) and transfected with <i>miR-138-5p</i> mimics or inhibitors. Calcification was evaluated via ALP and Alizarin Red staining. Western blot assessed osteogenic markers (RUNX2, ALP, OPN, BMP-2). Dual-luciferase assays confirmed <i>miR-138-5p</i> targeting of SLC39A14. The role of SLC39A14 and the Nrf2 pathway was examined through overexpression experiments and Western blot for Nrf2, HO-1, and NQO1. ML385 was used to inhibit Nrf2. <i>miR-138-5p</i> was significantly downregulated in CAVD tissues and OM-induced hAVICs. Overexpression of <i>miR-138-5p</i> inhibited calcification, reducing ALP activity, nodule formation, and osteogenic marker expression. Inhibition of <i>miR-138-5p</i> promoted calcification. SLC39A14, upregulated in CAVD, was validated as a direct target of <i>miR-138-5p</i>. Its overexpression promoted calcification, which was reversed by co-transfection with <i>miR-138-5p</i>. Mechanistically, <i>miR-138-5p</i> was associated with activation of the Nrf2 pathway, as evidenced by increased Nrf2 nuclear translocation and HO-1/NQO1 expression, whereas SLC39A14 overexpression showed the opposite effect. Nrf2 inhibition with ML385 diminished the anti-calcific effect of <i>miR-138-5p</i>. <i>miR-138-5p</i> inhibits hAVIC calcification, at least in part through regulation of SLC39A14 and the Nrf2 pathway, highlighting a potentially important regulatory mechanism in CAVD and a candidate therapeutic target for valve calcification.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783842","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":"SLC3A1 Mitigates Ferroptosis and Promotes Enzalutamide Resistance in Prostate Cancer","authors":"Peng Liu,&nbsp;Haocheng Zhang,&nbsp;Yuhang Qian,&nbsp;Jiong Zhang,&nbsp;Xiaojun Deng,&nbsp;Bin Sun","doi":"10.1002/jbt.71080","DOIUrl":"https://doi.org/10.1002/jbt.71080","url":null,"abstract":"<p>Prostate cancer (PCa) remains a leading cause of cancer-related mortality in aging male, with resistance to enzalutamide (Enza) representing a major therapeutic challenge. This study identifies SLC3A1 as a key driver of Enza resistance. Through integrative bioinformatics analysis of GEO datasets, we found <i>SLC3A1</i> significantly upregulated in Enza-resistant PCa models. WGCNA and single-cell RNA sequencing confirmed its association with adverse prognosis and activation of key survival pathways. Functional experiments demonstrated that <i>SLC3A1</i> knockdown reduced AKT phosphorylation, and inhibited colony formation in LNCaP cells. Conversely, <i>SLC3A1</i> overexpression activated PI3K-AKT signaling, suppressed ferroptosis and conferred Enza resistance in vitro and in vivo. These results reveal SLC3A1 is a promising therapeutic target for advanced prostate cancer.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753929","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":"Synthesis, Anticancer Evaluation, mRNA Expression Analysis, and Molecular Docking of Fluorinated Picolinamide–Benzothiazole Derivatives Against Breast Cancer-Related Genes CDK2, ERK2, and BCL2","authors":"Nagalakshmamma Vadabingi,&nbsp;Venkataswamy Mallepogu,&nbsp;Surendra Pothuraju,&nbsp;Chiranjeevi Pasala,&nbsp;Sumithra Poreddy,&nbsp;Uma Maheswari Amineni,&nbsp;Suresh Reddy Cirandur,&nbsp;Balaji Meriga","doi":"10.1002/jbt.71025","DOIUrl":"https://doi.org/10.1002/jbt.71025","url":null,"abstract":"<p>The present study focuses on the design, synthesis, characterization, and biological evaluation of two new series of derivatives 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide (<b>3a–e</b>) and 2-aminobenzothiazole (<b>5a-e</b>) as potential antioxidant and anticancer agents. The compounds were synthesized via a one-pot condensation reaction of 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide and 2-aminobenzothiazole with various phenyl isocyanates, isothiocyanates, and sulfonamides in the presence of triethylamine at 60°C. Reaction progress was monitored by TLC, and products were purified using column chromatography. Structural elucidation was achieved using FT-IR, ¹H NMR, ¹³C NMR, HRMS, and CHN analyses. Antioxidant activity, evaluated by DPPH and ABTS assays, revealed that compounds <b>3d</b> and <b>5b</b> exhibited the highest radical scavenging potential, with IC₅₀ values of 21.45 μg/mL and 20.05 μg/mL (DPPH) and 22.24 μg/mL and 21.98 μg/mL (ABTS), comparable to ascorbic acid. Cytotoxicity assessment by MTT assay demonstrated strong antiproliferative activity of <b>3d</b> and <b>5b</b> against MDA-MB-231 breast cancer cells (IC₅₀ = 22.13 μg/mL and 20.11 μg/mL), with minimal toxicity toward normal 3T3-L1 cells. Fluorescence microscopy and flow cytometry confirmed apoptosis profile induction and G2/M phase arrest. The qRT-PCR analysis showed significant down-regulation of Bcl-2, CDK2, and ERK2 gene expression, correlating with apoptotic activation. Molecular docking and MM-GBSA analyses revealed stable and high-affinity binding of <b>3d</b> and <b>5b</b> with Bcl-2, CDK2, and ERK2 proteins, supported by multiple hydrogen bonding and π–π interactions. Molecular dynamics simulations (150 ns) confirmed the structural stability of these complexes. Overall, compounds <b>3d</b> and <b>5b</b> emerged as promising dual-function ‘antioxidant and anticancer’ candidates and in vivo evaluations for therapeutic development.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753779","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":"Modulatory Role of Melatonin in Cyclophosphamide-Treated Platelets: Insights From Ex Vivo Oxidative Stress Model","authors":"Anusha Berikai Ananthakrishna,&nbsp;Magdaline Christina Rajanand,&nbsp;Vani Rajashekaraiah","doi":"10.1002/jbt.71079","DOIUrl":"https://doi.org/10.1002/jbt.71079","url":null,"abstract":"<p>Cyclophosphamide (CYP) is implicated in oxidative stress (OS)-related platelet destruction during chemotherapy, leading to thrombocytopenia. Antioxidants can potentially attenuate the side effects of drugs and improve therapeutic outcomes. Melatonin is highly permeable and has radical scavenging and antioxidant enzyme-stimulating activity. This study investigates the influence of melatonin on platelets during CYP-induced OS under ex vivo conditions. Platelets isolated from the whole blood of male Wistar rats (<i>n</i> = 5) were categorized and treated as follows: Controls (CON) and Experimentals: (i) CYP, (ii) melatonin (MEL), and (iii) CYP+melatonin (CYP + MEL). Antioxidant defenses, OS and platelet function markers were assessed. Catalase, total antioxidant capacity (TAC), and lactate dehydrogenase decreased; ATP secretion, activation and cell viability decreased; and glucose and aggregation increased in CYP compared to CON. Catalase, TAC and glucose were maintained in MEL compared to CON. However, catalase increased, thereby decreasing lipid peroxidation and enhancing activation and aggregation in CYP + MEL compared to CYP. Melatonin mitigates CYP-induced cellular damage by scavenging ROS and augmenting antioxidant defenses. Platelets possess a complex network of signaling cascades, and can serve as ex vivo models to study platelet dysfunction. They can provide insights into platelet behavior under simulated physiological and pathological conditions.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753923","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":"Fisetin Attenuates Amyloid-Beta-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells: Integrating In Silico Target Prediction and In Vitro Validation","authors":"Charu Jaiswal,&nbsp;Ishika Singh,&nbsp;Abhishek Kumar Singh","doi":"10.1002/jbt.71076","DOIUrl":"https://doi.org/10.1002/jbt.71076","url":null,"abstract":"<p>The accumulation of amyloid beta (Aβ) and tau tangles in the brain leads to Alzheimer's disease (AD). Fisetin, a natural flavonoid, is an antioxidant molecule, and its neuroprotective effects are not clearly understood. Therefore, attempts have been made to evaluate the neuroprotective effects of fisetin using in silico methods and an Aβ1-42-induced neurotoxicity model in human neuroblastoma SH-SY5Y cells. In silico studies demonstrated that fisetin binds strongly and with high stability to different proteins, such as ULK1 (autophagy marker), p21 (senescence/cell cycle marker), and synaptophysin (synaptic marker), which are responsible for maintaining brain health and are implicated in AD. Moreover, Aβ1-42 was also found to bind to these protein targets, indicating that Aβ1-42 and fisetin both target common binding sites. In vitro studies on SH-SY5Y cells further confirmed that fisetin promotes cell survival under the toxic effects of Aβ1-42. It reduced oxidative stress and restored the activities of ion channels, which were impaired by Aβ1-42 treatment. Fisetin increased antioxidant defense and restored the activity of molecules that control brain signals. Overall, fisetin acts on multiple targets to protect neurons by reducing oxidative damage, supporting ion channel activity, and inducing the autophagy process.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753928","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":"Iron-Sulfur Cluster Targeting: A Novel Perspective for Treating Alcohol-Related Lipid Metabolic Diseases","authors":"Li Xu,&nbsp;Zhenyang Xu,&nbsp;Chenli Su,&nbsp;Yanqian Zhao,&nbsp;Linjing Qiang,&nbsp;Xiayong Jing,&nbsp;Yuxiang Sun","doi":"10.1002/jbt.71082","DOIUrl":"https://doi.org/10.1002/jbt.71082","url":null,"abstract":"<p>Iron–sulfur (Fe–S) clusters are pivotal molecular cofactors bridging inorganic chemistry and organic life processes, with their tightly regulated biosynthesis and function underpinning cellular metabolic homeostasis. Chronic alcohol-induced metabolic stress impairs Fe–S cluster stability and biosynthesis via reactive oxygen species (ROS)-mediated oxidative damage and direct acetaldehyde toxicity, culminating in functional failure of this core cofactor. Current evidence is synthesized herein to delineate the hierarchical pathogenic cascade triggered by Fe–S cluster dysfunction. At the cellular level, Fe–S cluster depletion inactivates aconitase, driving citrate accumulation and redirecting carbon flux toward lipogenesis; concurrently, succinate dehydrogenase dysfunction causes succinate buildup, which epigenetically suppresses fatty acid oxidation. Impaired tRNA thiolation further compromises mitochondrial translational fidelity. Together, these defects precipitate an energy crisis and a self-perpetuating lipotoxicity–oxidative stress vicious cycle. At the systemic level, this metabolic dysregulation fuels disease progression from fatty liver and hyperlipidemia to atherosclerosis, mediated by enhanced hepatic VLDL secretion, reduced HDL levels, and oxidized LDL (Ox-LDL) formation. Furthermore, a hypothetical structural model for acetaldehyde-driven Fe–S cluster disintegration, grounded in organometallic chemistry principles. Collectively, this review highlights the central role of Fe–S clusters in alcohol-associated metabolic disorders and provides a novel theoretical framework for developing therapeutics targeting Fe–S cluster homeostasis.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753780","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":"Individual and Combined Cardioprotective Effects of 1,25(OH)2D3 and Dimethyl Fumarate in an Isoproterenol-Induced Myocardial Injury Model","authors":"Fatma Hande Karpuzoğlu,&nbsp;Serhat Kilinç,&nbsp;İlayda Sözmen,&nbsp;İlknur Bingül,&nbsp;Abdurrahman Fatih Aydin,&nbsp;Aysel Bayram,&nbsp;Semen Önder,&nbsp;Efe Akçe,&nbsp;Semra Doğru-Abbasoğlu,&nbsp;Müjdat Uysal","doi":"10.1002/jbt.71081","DOIUrl":"https://doi.org/10.1002/jbt.71081","url":null,"abstract":"<p>Acute myocardial infarction (AMI) is closely associated with excessive oxidative stress, inflammation, and activation of the renin–angiotensin system (RAS). The active form of vitamin D [1,25(OH)₂D₃] and the Nrf2 activator dimethyl fumarate (DMF) exhibit antioxidant and anti-inflammatory effects. This study investigated the individual and combined protective roles of 1,25(OH)₂D₃ and DMF in an isoproterenol (ISO)-induced model of myocardial injury. Male Sprague–Dawley rats received ISO (85 mg/kg, two doses 24 h apart) and were pretreated with 1,25(OH)₂D₃ or DMF alone, a combination pretreatment, or a combination post-treatment. Myocardial injury was assessed using serum biomarkers, histopathology, oxidative stress markers (ROS, MDA, GSH), inflammatory markers (TNF-α), RAS components (Ang II, AT1R, ACE), and mRNA expression of Nrf2, NQO1, and NF-κB. ISO administration caused marked myocardial injury, oxidative imbalance, and increased inflammatory and RAS activation while suppressing Nrf2 and NQO1. Both 1,25(OH)₂D₃ and DMF significantly reduced oxidative stress, inflammation, and components of the RAS. Combination pretreatment and post-treatment further improved redox status and molecular markers. These groups showed elevated Nrf2 and NQO1 expression and reduced NF-κB, AT1R, and ACE expression compared with ISO controls. However, synergistic enhancement was not observed. 1,25(OH)₂D₃ and DMF provide both preventive and therapeutic protection against ISO-induced myocardial injury by modulating oxidative stress, inflammation, the Nrf2 and NF-κB signaling pathways, and RAS regulation.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753833","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}