Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Combination of 5-Fluorouracil and Thymoquinone for Enhanced Cytotoxicity, Genotoxicity and Apoptosis In Colorectal Cancer: In Vitro and In Vivo Studies","authors":"Eray Metin Guler,&nbsp;Kubra Bozali,&nbsp;Onder Huseyinbas,&nbsp;Mert Celikten,&nbsp;Abdurrahim Kocyigit","doi":"10.1002/jbt.70276","DOIUrl":"https://doi.org/10.1002/jbt.70276","url":null,"abstract":"<p>Research on the effects of herbal-derived natural active substances on cancer treatment and their combination with conventional treatments has intensified. This study analyzed the cytotoxic, genotoxic, apoptotic, and anticancer effects of combined treatment with 5-Fluorouracil (5-FU) and thymoquinone (TQ) on colorectal cancer. Cytotoxicity was evaluated using the ATP assay, DNA damage was assessed through the comet assay, apoptosis was measured via acridine orange/ethidium bromide staining and annexin V-FITC dye, and the expression of proapoptotic and antiapoptotic proteins was determined by western blot analysis. Transfected LoVo cells were injected subcutaneously into nude mice, and following treatment, oxidative stress and inflammation markers were examined in blood samples, while growth factors and vascularization markers were analyzed in tissue samples. The combination therapy at low concentrations resulted in increased cytotoxicity, DNA damage, apoptosis, and intracellular reactive oxygen species (<i>p</i> &lt; 0.001), while simultaneously decreasing mitochondrial membrane potential and glutathione levels (<i>p</i> &lt; 0.001), in comparison to monotherapy with TQ or 5-FU. Additionally, tissue levels of TGF-β1 and VEGF-α were significantly reduced (<i>p</i> &lt; 0.001). Results demonstrates that while TQ or 5-FU alone have notable anticancer effects, their combination offers greater efficacy in mitigating molecular changes in both In Vitro and In Vivo models. Future studies should focus on optimizing the formulation, understanding the molecular mechanisms, and evaluating the efficacy and safety of the TQ and 5-FU combination across different cancer types.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889111","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":"Quercetin Mitigates Sulfasalazine-Induced Toxicity by Inhibiting p53-Dependent Apoptosis and DNA Damage in Rat Epididymis, Semen and Bone Marrow","authors":"Sharon O. Osawe,&nbsp;Ebenezer O. Farombi","doi":"10.1002/jbt.70277","DOIUrl":"https://doi.org/10.1002/jbt.70277","url":null,"abstract":"<div>\u0000 \u0000 <p>Sulfasalazine, an anti-inflammatory drug used in the treatment of inflammatory bowel disorders poses a threat to male reproductive potential. With a growing interest in the therapeutic ability of dietary flavonoids to mitigate drug-related reproductive dysfunction in males, we evaluated the possible protective potentials of quercetin against sulfasalazine-induced genotoxicity in the bone marrow and apoptosis in testis, semen, and epididymis of Wistar rats. Twenty rats were placed into four groups (<i>n</i> = 5) and orally administered the following for 14 consecutive days: Group 1: 0.5% sodium carboxymethyl cellulose (1 ml/kg). Group 2: quercetin (20 mg/kg). Group 3: sulfasalazine (600 mg/kg). Group 4: sulfasalazine (600 mg/kg) + quercetin (20 mg/kg). Tumor suppressor protein (Tp53), caspase 9, and caspase 3 levels were increased in semen, while TUNEL positive sperm increased in epididymis of sulfasalazine-treated rats, indicative of apoptotic death of sperm. These were significantly decreased in sulfasalazine-treated rats co-administered with quercetin. However, levels of Tp53, caspase 9 and 3 remained unchanged, while TUNEL-stained sperm cells were not evident in testes of rats treated with sulfasalazine. Again, sulfasalazine increased the frequency of micronuclei (MN) in bone marrow of treated rats, evident of its genotoxic potential. MN frequency was, however, decreased in their bone marrow on co-administration of quercetin. In conclusion, our findings suggest that quercetin holds promise in ameliorating the apoptotic death of sperm cells associated with sulfasalazine's detrimental effect on male fertility and DNA.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884159","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":"Knockdown of circRNA_0030042 Attenuates Heart Failure via miR-568/PRG4 Pathway","authors":"Li-li Wang,&nbsp;Hong-mei Yao,&nbsp;Xing-xing Zhao,&nbsp;Xiao-wei Yin,&nbsp;Jin-sheng Tian","doi":"10.1002/jbt.70267","DOIUrl":"https://doi.org/10.1002/jbt.70267","url":null,"abstract":"<div>\u0000 \u0000 <p>Heart failure is a common heart disease and cause of death globally which is caused by structural and functional abnormalities. circRNA_0030042 is a newly discovered circRNA that derived from its host gene forkhead box O1 (FOXO1). However, the role of circRNA_0030042 in heart failure is not revealed. This study aims to explore the role of circRNA_0030042 in heart failure progression. In this study, AC16 cell heart failure model was induced in a medium containing 200 µM H₂O₂. circRNA_0030042 was markedly elevated in peripheral blood from patients with heart failure and H₂O₂-induced AC16 cells. Knockdown of hsa-circRNA_0030042 repressed the apoptosis of H₂O₂-induced AC16 cells and facilitated the viability of H₂O₂-induced AC16 cells. Besides, knockdown of hsa-circRNA_0030042 decreased iron ion level, ferroptotic markers ROS and MDA levels, increased GSH level, ferroptosis-associated proteins SLC7A11 and GPX4 protein expressions in H₂O₂-induced AC16 cells. In addition, hsa-circRNA_0030042 could interact with miR-568, and negatively modulate miR-568 expression in AC16 cells. miR-568 also targeted PRG4, and negatively modulated PRG4 expression. hsa-circRNA_0030042 positively regulated PRG4 via miR-568 in AC16 cells. Furthermore, knockdown of circRNA_0030042 promoted the proliferation, repressed the iron ion level, ROS level, increased SLC7A11 and GPX4 protein expressions in H₂O₂-induced AC16 cells via miR-568/PRG4 pathway. Finally, transverse aortic constriction (TAC) mice model were conducted by a thoracotomy procedure under the microscope. In vivo experiments showed that knockdown of mmu-circRNA_0030042 ameliorated cardiac dysfunction, decreased myocardial injury markers cTnI, CK-MB and BNP levels, relieved cardiac histopathological damage, decreased the apoptosis of heart tissue, and increased GSH, SLC7A11 and GPX4 protein expressions in heart tissue of TAC mice. Therefore, knockdown of circRNA_0030042 attenuated heart failure via miR-568/PRG4 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883858","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":"Enhancing Male Fertility: The Role of Crocin in Boosting Sperm Motility Through Antioxidant Activity and Mitochondrial Pathways","authors":"Manel Boussabbeh,&nbsp;Manel Haddar,&nbsp;Amira Sallem,&nbsp;Abir Chaieb,&nbsp;Rania Khdhiri,&nbsp;Salwa Abid-Essefi,&nbsp;Meriem Mehdi","doi":"10.1002/jbt.70275","DOIUrl":"https://doi.org/10.1002/jbt.70275","url":null,"abstract":"<div>\u0000 \u0000 <p>Excessive production of reactive oxygen species (ROS) is a critical factor adversely affecting semen quality, particularly sperm motility. Crocin, a key compound of <i>Crocus Sativus</i> (saffron), is recognized for its antioxidant properties. This study aimed to investigate the potential of crocin to improve in vitro sperm motility in case of asthenozoospermia. Sperm samples from 95 patients with asthenozoospermia were incubated for 3 h at 37°C with varying concentrations of crocin (0, 0.2, 0.5, 1, or 1.5 mM). Sperm motility was assessed using time-lapse video microscopy. Intracellular ROS levels were evaluated through the DCFH-DA assay while ROS-induced damage was quantified through lipid peroxidation and carbonylated proteins levels. Catalase, superoxide dismutase, and glutathione peroxidase were analyzed. Additionally, mitochondrial function was assessed via mitochondrial activity via MTT assay and potential via Rh123 assay. Our findings revealed a significant increase in sperm velocity by 93% (G1) and 91% (G2) and in the distance traveled by motile spermatozoa by 76.5% (G1) and 72.1% (G2) (<i>p</i> &lt; 0.001). ROS levels decreased by 1.5-fold (G1) and 2.4-fold in (G2) (<i>p</i> &lt; 0.001), while malondialdehyde levels dropped twofold (G1) and 3.4-fold (G2) (<i>p</i> &lt; 0.001). Carbonylated protein content decreased by 2.8-fold (G1) and threefold (G2) (<i>p</i> &lt; 0.001). Improvements also included succinate dehydrogenase activity (2.14-fold in G1, 1.85-fold in G2, <i>p</i> &lt; 0.001) and mitochondrial membrane potential (1.7-fold in G1, 1.9-fold in G2, <i>p</i> &lt; 0.001). These findings highlight crocin's potential to enhance sperm motility and reduce oxidative stress in asthenozoospermic samples.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884158","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":"Effects of PM2.5 Metal Components Derived From Porcine Farm Exposure on Sperm Function in Mice","authors":"Chae Yeon Kim,&nbsp;Chae Rim Kim,&nbsp;Eungyung Kim,&nbsp;Kanghyun Park,&nbsp;Hyeonjin Kim,&nbsp;Lei Ma,&nbsp;Ke Huang,&nbsp;Zhibin Liu,&nbsp;Junsu Park,&nbsp;Minwoong Jung,&nbsp;Shengqing Li,&nbsp;Weihong Wen,&nbsp;Sangsik Kim,&nbsp;Sijun Park,&nbsp;Zae Young Ryoo,&nbsp;Junkoo Yi,&nbsp;Myoung Ok Kim","doi":"10.1002/jbt.70279","DOIUrl":"https://doi.org/10.1002/jbt.70279","url":null,"abstract":"<p>This study aimed to identify the effects of major metal components present in particulate matter (PM)2.5 on the reproductive system, sperm function, and embryo development. Through intratracheal instillation, male mice were exposed to various concentrations of metal components, including calcium oxide (Ca), iron oxide (Fe), aluminum oxide (Al), zinc oxide (Zn), lead oxide (Pb), and a mixture of these metals, in PM2.5 collected from the porcine farm. After 14 days, testicular inflammation and abnormal sperm morphology were observed in the exposed mice. These results indicate that such metal exposure enhances inflammatory cytokines in the testis and oxidative stress-induced apoptosis. Moreover, the exposure influenced sperm deformation, capacitation status, testosterone levels, and testosterone biosynthesis. Importantly, embryo development was also found to be impacted due to decreased sperm fertility. This study demonstrates that major metal components of PM2.5 derived from porcine farm pose adverse effects on the male reproductive system.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883859","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-186-5p Down-Regulates PD-L1 Level in Acute Myeloid Leukemia Cells and Inhibits Tumorigenesis and Immune Escape","authors":"Cheng Lian,&nbsp;Yanhui Liu,&nbsp;Pingchong Lei","doi":"10.1002/jbt.70278","DOIUrl":"https://doi.org/10.1002/jbt.70278","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is a malignant tumor of blood cells, which seriously interferes with the generation of normal cells. Although miR-186-5p is diminished in AML, its exact mechanism is not well understood. miR-186-5p and PD-L1 levels in AML cells (HL-60, KG-1, TF-1a, MOLT-3) and subcutaneous tumor tissue were discovered through qRT-PCR and Western blot. miR-186-5 p and PD-L1 combining sites were foreseen by the database and verified by dual luciferase and immunoprecipitation experiments. AML cells with miR-186-5p overexpression or knockdown and PD-L1 overexpression were cocultured with CD4⁺ and CD8⁺ T cells. The proliferation, migration, invasion and apoptosis of AML cells, CD8⁺ and CD4⁺ T cell growth and apoptosis, and activated markers (Perforin and Granzyme B) and secreted cytokines (IFN-γ, IL-4 and TNF-α) levels were detected by CCK8, Transwell, flow cytometry, CFSE, Western blot and ELISA, respectively. Subcutaneous xenograft magnitude and mass in nude mice were measured. Ki67 level was identified through immunohistochemistry. CD4⁺ and CD8⁺ T cell level and infiltration were detected by immunofluorescence and flow cytometry. miR-186-5p was downregulated, and PD-L1 was boosted in AML cells and subcutaneous tumor tissues (<i>p</i> &lt; 0.05), while miR-186-5p targeted down-regulate PD-L1. miR-186-5p upregulation hindered AML cell multiplication, migration, invasion and facilitate cell death, and enhanced the proliferation activity, activation markers (Perforin and Granzyme B) and secreted cytokines (IFN-γ, IL-4, TNF-α) of CD8⁺ and CD4⁺ T cells, inhibited apoptosis, and inhibited immune escape (<i>p</i> &lt; 0.05). Knockdown of miR-186-5p can promote AML progression, but PD-L1 upregulation weakens the antitumor impact of miR-186-5p overexpression (<i>p</i> &lt; 0.05). Transplanted tumor mice experiments also found that miR-186-5p hindered PD-L1 and tumor growth (<i>p</i> &lt; 0.05). In conclusion, miR-186-5p can target inhibit PD-L1, suppress AML cells multiplication, movement, invasion and immune escape, and then reduce AML, aiming to provide support and basis for the pathological mechanism and prevention and treatment strategy of AML.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875649","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":"RETRACTION: The Pyrethroid Insecticide Permethrin Confers Hepatotoxicity Through DNA Damage and Mitochondria-Associated Apoptosis Induction in Rat: Palliative Benefits of Fumaria Officinalis","authors":"","doi":"10.1002/jbt.70250","DOIUrl":"https://doi.org/10.1002/jbt.70250","url":null,"abstract":"<p><b>RETRACTION:</b> N. Aoiadni, N. Chiab, H. Jdidi, R.G. Bouzid, A. El Feki, H. Fetoui, and F.G. Koubaa, “The Pyrethroid Insecticide Permethrin Confers Hepatotoxicity Through DNA Damage and Mitochondria-Associated Apoptosis Induction in Rat: Palliative Benefits of <i>Fumaria officinalis, ” Journal of Biochemical and Molecular Toxicology</i> 36, no. 10 (2022): e23172, http://doi.org/10.1002/jbt.23172.</p><p>The above article, published online on 21 July 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Hari K. Bhat, and Wiley Periodicals, LLC. The retraction has been agreed due to unattributed reuse of data and images in Table 4, Table 5, Figure 2A, and Figure 4 from the authors' previously published work. The authors were not able to provide a satisfactory explanation for this reuse and therefore, the article must be retracted. The authors did not respond to this decision.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871872","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":"Therapeutic Potential of Exosomal miRNAs: New Insights and Future Directions","authors":"Haili Duan,&nbsp;Seyedeh Helya Siadat,&nbsp;Saade Abdalkareem Jasim,&nbsp;Pooja Bansal,&nbsp;Harpreet Kaur,&nbsp;Maytham T. Qasim,&nbsp;Munther Kadhim Abosaoda,&nbsp;Raed Fanoukh Aboqader Al-Aouadi,&nbsp;Muath Suliman,&nbsp;payam Ali khiavi","doi":"10.1002/jbt.70270","DOIUrl":"https://doi.org/10.1002/jbt.70270","url":null,"abstract":"<div>\u0000 \u0000 <p>Modern advancements in medicine include developing targeted drug delivery systems in the medical field, which are designed to unravel the potential of therapeutic products and overcome the barriers to the effectiveness of current approaches. Various nanopolymer carrier systems have been introduced in this regard, and the simple characteristics of extracellular vesicles have drawn special attention to their application as an effective drug delivery tool. Exosomes are very similar to transport vesicles and have a lipid-biomembrane covering an aqueous core. They also contain both hydrophilic and lipophilic substances and deliver their cargo to the desired targets. These properties enable exosomes to overcome some of the limitations of liposomes. Exosomes can easily diffuse into body fluids and remain in the bloodstream for a long time, crossing physiological barriers and entering cells. Exosomes, which contain a large volume of biomolecules, do not stimulate immune responses and do not accumulate in the liver or lungs instead of target tissues. Recent advancements in regenerative medicine have enabled scientists to utilize exosomes extracted from mesenchymal stem cells (MSCs), which possess significant regenerative abilities, for treating various diseases. The contents of these exosomes are crucial for both diagnosis and treatment, as they influence disease progression. Numerous in vitro studies have confirmed the safety, effectiveness, and therapeutic promise of exosomes in conditions such as cancer, neurodegenerative disorders, cardiovascular issues, and orthopedic ailments. This article explores the therapeutic potential of MSC-derived exosomes and outlines the essential procedures for their preparation.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865627","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":"Salvianolic Acid A Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Activating AMPK/SIRT1/Nrf2 Signaling Pathway","authors":"Pengwei Wang,&nbsp;Yu Sun,&nbsp;Ru Zhang,&nbsp;Yongli Guo,&nbsp;Yongheng Zhang,&nbsp;Shengjie Guo,&nbsp;Yemin Wang,&nbsp;Jianlian Gao,&nbsp;Pengfei Yang,&nbsp;Zhijian Deng","doi":"10.1002/jbt.70282","DOIUrl":"https://doi.org/10.1002/jbt.70282","url":null,"abstract":"<div>\u0000 \u0000 <p>Salvianolic acid A (Sal A) has been reported to have anti-inflammatory and antioxidant properties. The present study aimed to explore the potential mechanisms of Sal A on lipopolysaccharide (LPS)-induced acute lung injury (ALI). The results indicated that Sal A pretreatment attenuated LPS induced lung injury, shown by alleviated histopathological damage and alveolar-capillary barrier dysfunction, as well as reduced inflammatory response and oxidative stress. Moreover, Sal A pretreatment effectively increased the expression of p-AMPK and SIRT1 and promoted Nrf2 nuclear translocation in lung tissues. However, these effects were remarkably blunted by Compound C. Molecular docking experiments further confirmed that Sal A bound well to the active sites of AMPK and SIRT1. In conclusion, these results indicated that Sal A exerted its protective effects on LPS-induced ALI through suppressing inflammation and oxidative stress, which was mainly dependent on the activation of AMPK/SIRT1/Nrf2 signaling pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865628","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":"Sevoflurane Preconditioning Protects Against Myocardial Ischemia Reperfusion Injury in Mice via PI3K/AKT/GSK3β-mediated Upregulation of Syntaxin1a","authors":"Meng Liu,&nbsp;Fengying Xu,&nbsp;Jinjin Lv,&nbsp;Xiaofeng Liu,&nbsp;Eerdun Wang","doi":"10.1002/jbt.70260","DOIUrl":"https://doi.org/10.1002/jbt.70260","url":null,"abstract":"<div>\u0000 \u0000 <p>Preconditioning with volatile anesthetics, such as isoflurane and sevoflurane, can protect the myocardium against ischemia/reperfusion injury (IRI). Syntaxin1A (Stx1A) is cardioprotective and regulated by volatile anesthetics. However, is the mechanism by which sevoflurane preconditioning (SPC) induces Stx1A to exert myocardial protection remains unclear. The study investigates whether SPC induces upregulation of Stx1A through the thymoma viral proto-oncogene (AKT)/Glycogen synthase kinase 3 β (GSK3β) signaling pathway. Myocardial IRI model in mice was established by surgically ligating the left anterior descending coronary followed by loosening of the occlusion. Regulation of signaling pathway by intraperitoneal administration of the phosphatidylinositol 3-kinase (PI3K) inhibitor, Ly294002 (30 mg/kg), and GSK3β inhibitor, TWS119 (30 mg/kg). The triphenyl tetrazolium chloride (TTC) staining method was used to measure the myocardial infarction area. Serum creatine kinase MB (CK-MB) and lactic dehydrogenase (LDH) concentration were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to examine AKT/GSK3β pathway activity, as well as expressions of Stx1A, small ubiquitin-like modifier 1 (SUMO1), growth hormone-releasing hormone (GHRH), or calcitonin gene-related peptide (CGRP), and brain natriuretic peptide (BNP). Both IRI and SPC induced upregulation of Stx1A in mice. However, the upregulation was abolished by treatment with Ly294002, while TWS119 further increased its expression (<i>p</i> &lt; 0.05). Myocardial infarct area, serum CK-MB, and LDH were elevated in the IRI group but were inhibited by SPC-induced (<i>p</i> &lt; 0.05); however, this inhibition by SPC was eliminated by Ly294002 (<i>p</i> &lt; 0.05). TWS119 causes the opposite effect (<i>p</i> &lt; 0.05). These findings demonstrated that SPC activated the AKT/GSK3β signaling pathway to upregulate Stx1A expression and provide protection to the myocardium.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861831","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}