Journal of Biochemical and Molecular Toxicology最新文献_第5页

Protective Effects of Chrysin Against Diclofenac-Induced Nephrotoxicity in Rats via Attenuation of Oxidative Stress, Apoptosis and Endoplasmic Reticulum Stress 菊花素通过抑制氧化应激、细胞凋亡和内质网应激对双氯芬酸所致大鼠肾毒性的保护作用

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-19 DOI: 10.1002/jbt.70373

Cuneyt Caglayan, İzzettin Ekinci, Cihan Gur, Adnan Ayna, İbrahim Bayav, Fatih Mehmet Kandemir

{"title":"Protective Effects of Chrysin Against Diclofenac-Induced Nephrotoxicity in Rats via Attenuation of Oxidative Stress, Apoptosis and Endoplasmic Reticulum Stress","authors":"Cuneyt Caglayan, İzzettin Ekinci, Cihan Gur, Adnan Ayna, İbrahim Bayav, Fatih Mehmet Kandemir","doi":"10.1002/jbt.70373","DOIUrl":"https://doi.org/10.1002/jbt.70373","url":null,"abstract":"Diclofenac (DCL) is a broadly prescribed non-steroidal anti-inflammatory drug (NSAID) for pain management and has been linked to nephrotoxicity despite its therapeutic benefits. This study provides new insights into the palliative impacts of chrysin (CH) against DCL-induced kidney damage by modulating oxidative injury, endoplasmic reticulum (ER) stress and apoptosis. The rats were divided into five groups: the control group (Group 1), CH-only group (50 mg/kg, Group 2), DCL-only group (50 mg/kg, Group 3), DCL + CH (25 mg/kg, Group 4), and DCL + CH (50 mg/kg, Group 5). DCL injection led to significant renal damage marked by elevated serum urea, creatinine and malondialdehyde (MDA) levels, reduced glutathione (GSH) concentration, and decreased activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase). The mRNA expression levels of Ho-1 and Nrf2 were also suppressed. Additionally, DCL treatment triggered apoptosis as evidenced by increased expression of Bax and caspase-3 alongside decreased Bcl-2 expression. Furthermore, DCL induced ER stress was confirmed by upregulation of Perk, Ire1, Atf-6, and Grp78 transcription levels. Also, it was demonstrated that DCL treatment upregulated Mmp2 and Mmp9 levels. Treatment with CH significantly mitigated these adverse effects suggesting that CH effectively protects DCL-induced kidney toxicity by targeting multiple pathways. In summary, this study highlights the importance of CH as a promising therapeutic agent for alleviating kidney damage associated with DCL toxicity.","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314965","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}

引用次数: 0

Growth Inhibition Activity Assessment of γ-Lactam-Containing Chemicals in Cultured MCF-7 Cells and Xenografted Chick Embryos 含γ-内酰胺化学物质对MCF-7细胞和异种移植鸡胚生长抑制活性的评价

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-17 DOI: 10.1002/jbt.70344

Chiao-Yin Sun, Shu-Chun Cheng, Yun-Hsin Wang, Ching-Yuan Huang, Adam Shih-Yuan Lee, Tao-Sheng Li, Ta-Hsien Lin, Yau-Hung Chen

{"title":"Growth Inhibition Activity Assessment of γ-Lactam-Containing Chemicals in Cultured MCF-7 Cells and Xenografted Chick Embryos","authors":"Chiao-Yin Sun, Shu-Chun Cheng, Yun-Hsin Wang, Ching-Yuan Huang, Adam Shih-Yuan Lee, Tao-Sheng Li, Ta-Hsien Lin, Yau-Hung Chen","doi":"10.1002/jbt.70344","DOIUrl":"https://doi.org/10.1002/jbt.70344","url":null,"abstract":"<div>\u0000 \u0000 We evaluated the growth-inhibitory effects of three γ-butyrolactam (γ-lactam) derivatives (compounds 5, 6, and 8) on human breast cancer cells (MCF-7) and in a xenografted chick model. Growth inhibition was assessed using MTT assays and flow cytometry for compounds 5, 6, and 8, followed by Western blot analysis to examine the expression levels of cell cycle-associated proteins. Chick embryos were utilized as a xenograft model for further validation. The results revealed that compound 8 exhibited relatively low toxicity among the tested compounds. Western blot analysis suggested that compounds 5, 6, and 8 may be involved in the EGFR and P53 signaling pathways. In the xenograft model, compound 8 significantly inhibited MCF-7 tumor growth in chick embryos (tumor size in control group: 1.97 ± 0.69 mm, n = 15; compound 8-treated group: 1.20 ± 0.37 mm, n = 15). These findings suggest that compound 8 effectively inhibits MCF-7 growth with minimal toxicity, warranting further investigation in mammalian models.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309149","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}

引用次数: 0

Dimethyl Fumarate Ameliorates Collagen-Induced Arthritis in Lewis Rats by Modulation of Th17/Treg Balance 富马酸二甲酯通过调节Th17/Treg平衡改善Lewis大鼠胶原诱导关节炎

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-17 DOI: 10.1002/jbt.70345

Ali Sheikhian, Parisa Zafari, Mozhgan Faraji Talooki, Mahnaz Babaahmadi, Behnoosh Tayebi, Alimohammad Varzi, Alireza Rafiei

{"title":"Dimethyl Fumarate Ameliorates Collagen-Induced Arthritis in Lewis Rats by Modulation of Th17/Treg Balance","authors":"Ali Sheikhian, Parisa Zafari, Mozhgan Faraji Talooki, Mahnaz Babaahmadi, Behnoosh Tayebi, Alimohammad Varzi, Alireza Rafiei","doi":"10.1002/jbt.70345","DOIUrl":"https://doi.org/10.1002/jbt.70345","url":null,"abstract":"<div>\u0000 \u0000 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects approximately 1% of the world's population. Due to its anti-inflammatory effects, Dimethyl fumarate (DMF) can be used to treat RA. However, its molecular mechanisms have not yet been fully elucidated. In this study, an animal model of collagen-induced arthritis (CIA) was used to investigate DMF's In Vivo effects and probable mechanism of action on arthritis.\u0000 Twenty-five rats were divided into five groups: healthy control group (normal), CIA rats without any treatment (CIA control), CIA rats treated with vehicle, CIA rats treated with methotrexate (MTX), and CIA rats treated with DMF. Hind paw swelling and arthritis score were measured to evaluate DMF effects on the disease progression. Rats were killed on day 28; the plasma levels of IL-17, IL-10, and anti-collagen type II (CII) were measured by the ELISA method, and the percentage of Th17 and Treg cells in different groups was determined by flow cytometry.\u0000 DMF significantly reduced the arthritis score, hind paw swelling, cartilage destruction, and joint inflammation in CIA rats. The level of CII and IL-17 was also lower in the DMF-treated group compared to the untreated group. The level of IL-10 was higher in the DMF-treated rats. Furthermore, the percentage of Th17 was lower, and the percentage of Treg was higher in DMF-treated rats compared to the control group.\u0000 DMF demonstrated anti-arthritic activity by reducing the arthritis score, hind paw swelling, cartilage destruction, joint inflammation, and modulation of Treg/Th17 cells. Therefore, DMF may be considered as a new therapeutic agent in RA.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309148","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}

引用次数: 0

Synthesis and Biological Assessment of Cyanopyridine-Based 1,3,4-Oxadiazole Derivatives: Anticancer Potential, Antioxidant Activity, Molecular Docking, and DFT Calculations 基于氰吡啶的1,3,4-恶二唑衍生物的合成和生物学评价：抗癌潜力、抗氧化活性、分子对接和DFT计算

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-17 DOI: 10.1002/jbt.70346

Zineddine Zebbiche, Güldeniz Şekerci, Boulebd Houssem, Fatümetüzzehra Küçükbay, Suat Tekin, Hasan Küçükbay, Boudjemaa Boumoud

{"title":"Synthesis and Biological Assessment of Cyanopyridine-Based 1,3,4-Oxadiazole Derivatives: Anticancer Potential, Antioxidant Activity, Molecular Docking, and DFT Calculations","authors":"Zineddine Zebbiche, Güldeniz Şekerci, Boulebd Houssem, Fatümetüzzehra Küçükbay, Suat Tekin, Hasan Küçükbay, Boudjemaa Boumoud","doi":"10.1002/jbt.70346","DOIUrl":"https://doi.org/10.1002/jbt.70346","url":null,"abstract":"A series of six novel cyanopyridine derivatives bearing a 1,3,4-oxadiazole ring have been synthesized and characterized by FTIR, 13C NMR, 1H NMR, and elemental analysis. DFT calculations were carried out to determine their molecular geometries, electronic properties, and chemical reactivity. Their cytotoxicity has been evaluated against MCF-7 and CaCo-2 human cancer cell lines using the MTT assay. Most compounds displayed poor cytotoxic activity against the MCF-7 cell line except for compound 4e, which showed potent activity with IC50 = 8.352 µM. However, the CaCo-2 cell line was highly sensitive toward most tested compounds with an IC50 range from 2.612 µM to 8.394 µM except for compound 4 d. Molecular docking studies targeting human topoisomerase-IIβ revealed that all compounds exhibited excellent binding affinity within the enzyme's active site, with binding energies ranging from −7.33 to −8.28 kcal/mol. These findings suggest a potential anticancer mechanism underlying the observed cytotoxic activities. All tested compounds revealed low antioxidant activity in the DPPH assay. However, compounds 5b and 5 d presented moderate metal chelating activity. These findings underscore the potential anticancer properties of the synthesized cyanopyridine derivatives.","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309150","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}

引用次数: 0

Oncolytic Virus as a New Treatment Technology in Cancer 溶瘤病毒作为治疗癌症的新技术

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI: 10.1002/jbt.70352

Mohammed Asiri, Hussein Riyadh Abdul Kareem Al-Hetty, Reham Abdullah Al-Dhelaan, Soha Said Zakaria Shehata, Ashok Kumar Bishoyi, Raghav Vashishth, Subasini Uthirapathy, Kandi Satyam Naidu, Renu Arya, Zainab Ali-Hussein

{"title":"Oncolytic Virus as a New Treatment Technology in Cancer","authors":"Mohammed Asiri, Hussein Riyadh Abdul Kareem Al-Hetty, Reham Abdullah Al-Dhelaan, Soha Said Zakaria Shehata, Ashok Kumar Bishoyi, Raghav Vashishth, Subasini Uthirapathy, Kandi Satyam Naidu, Renu Arya, Zainab Ali-Hussein","doi":"10.1002/jbt.70352","DOIUrl":"https://doi.org/10.1002/jbt.70352","url":null,"abstract":"<div>\u0000 \u0000 Oncolytic viruses (OVs) are promising antineoplastic agents, leveraging unique capacities of certain viruses to specifically damage malignant cells without affecting normal tissues. Current article explores the mechanisms by which OVs exploit the dysregulated biology of cancer cells, leading to tumor regression and enhanced immune responses. Recent advancements in genetic engineering have led to developing modified viruses that can deliver therapeutic genes or immune-stimulatory proteins, further amplifying their antitumor effects. Clinical trials have demonstrated manageable safety profiles, with OVs therapies showing potential for durable responses through the induction of immunogenic cell death and long-term immune memory. However, challenges such as the hostile tumor microenvironment and the need for predictive biomarkers remain critical barriers to widespread clinical application. This article discusses ongoing research aimed at overcoming these challenges, including combination therapies with checkpoint inhibitors and strategies to enhance viral delivery. Integrating OV into existing treatment paradigms can significantly improve patient outcomes across diverse malignancies. This review highlights the transformative capacity of OV therapy as a cornerstone of future treatment strategies.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292928","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}

引用次数: 0

Synthesis, Biological Evaluation, in Silico ADMET Prediction, Molecular Docking and Dynamics Studies of 4-phenoxyphenyl-thiazole-Schiff Base Derivatives 4-phenoxyphenyl-噻唑- schiff碱衍生物的合成、生物学评价、ADMET预测、分子对接和动力学研究

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI: 10.1002/jbt.70362

Setu Karmokar, Monika Das, Sumita Saznin Marufa, Sohana Afrin, Joya Rani Debnath, Mohammad Sayed Alam, Hiroshi Nishino, Md. Aminul Haque, Mohammad Mostafizur Rahman

{"title":"Synthesis, Biological Evaluation, in Silico ADMET Prediction, Molecular Docking and Dynamics Studies of 4-phenoxyphenyl-thiazole-Schiff Base Derivatives","authors":"Setu Karmokar, Monika Das, Sumita Saznin Marufa, Sohana Afrin, Joya Rani Debnath, Mohammad Sayed Alam, Hiroshi Nishino, Md. Aminul Haque, Mohammad Mostafizur Rahman","doi":"10.1002/jbt.70362","DOIUrl":"https://doi.org/10.1002/jbt.70362","url":null,"abstract":"<div>\u0000 \u0000 A series of novel thiazole-Schiff base analogs (2a-2i) were synthesized through a multicomponent reaction involving thiosemicarbazide, 4-phenoxybenzaldehyde, and α-haloketone/phenacyl bromide derivatives. IR, 1H NMR, and HRMS spectroscopic techniques characterized the newly synthesized derivatives. These compounds were subsequently employed for their antimicrobial and antioxidant activities using agar disc diffusion and DPPH free radical scavenging methods. The multi-faceted activity of compound 2c was revealed in both In Vitro experiments. It exhibited the highest potency against Bacillus subtilis (26.0 ± 1.0 mm) and Aspergillus niger (22.3 ± 0.6 mm) which exceeded the inhibitory value of standard ceftriaxone (20.7 ± 0.6 mm) and amphotericin B (8.7 ± 0.6 mm), respectively. Additionally, 2c demonstrated a remarkable sevenfold increase in antioxidant capability (IC50 = 7.17 ± 2.61 µg/mL) compared to the standard ascorbic acid (IC50 = 49.69 ± 19.18 µg/mL). The in silico ADMET prediction demonstrated that most synthesized compounds adhered to Lipinski's rule of five and Veber's rule, with 2i being the exception with one violation. Molecular docking studies and dynamics simulation were conducted to explore potential binding sites, interactions, and stability of the ligand-protein complexes, providing insights aligned with the In Vitro results.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292488","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}

引用次数: 0

RNA-Binding Protein DHX9 Enhances Radioresistance in Metastatic Hepatocellular Carcinoma by Activation of the PI3K/Akt Pathway Through Enhanced EEF1A2 mRNA Stability rna结合蛋白DHX9通过增强EEF1A2 mRNA稳定性激活PI3K/Akt通路增强转移性肝细胞癌的放射耐药

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI: 10.1002/jbt.70356

HaiBo Wang, Wei Cui

{"title":"RNA-Binding Protein DHX9 Enhances Radioresistance in Metastatic Hepatocellular Carcinoma by Activation of the PI3K/Akt Pathway Through Enhanced EEF1A2 mRNA Stability","authors":"HaiBo Wang, Wei Cui","doi":"10.1002/jbt.70356","DOIUrl":"https://doi.org/10.1002/jbt.70356","url":null,"abstract":"<div>\u0000 \u0000 This study elucidated the role of Eukaryotic Elongation Factor 1 Alpha 2 (EEF1A2) and RNA-binding protein DExH-Box helicase 9 (DHX9) in hepatocellular carcinoma (HCC) radioresistance and molecular mechanisms. HCC tissues were compared with adjacent normal liver tissues by bioinformatics analysis. Clinical samples were evaluated according to RECIST 1.1 criteria. Regulatory interactions between EEF1A2 and DHX9 were analyzed. The effect of targeting these genes on HCC radioresistance was assessed. EEF1A2 was significantly elevated in radiation-resistant HCC tissues and cell lines. EEF1A2 overexpression was associated with enhanced cellular proliferation, reduced apoptosis, increased metastatic potential. Decreasing EEF1A2 significantly improved radiosensitivity. DHX9 stabilized EEF1A2 mRNA and increased EEF1A2 expression. Inhibition of DHX9 produced similar radiosensitizing effects as those observed with EEF1A2 knockdown. The interaction between DHX9 and EEF1A2 activated the PI3K/Akt pathway. The DHX9/EEF1A2 axis plays a pivotal role in the radioresistance of HCC by modulating the PI3K/Akt pathway.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292927","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}

引用次数: 0

Klotho Regulates the Extracellular Matrix Metabolism via TGF-β1/Wnt Signaling Pathway of Fibroblasts in Pelvic Organ Prolapse Klotho通过成纤维细胞TGF-β1/Wnt信号通路调控盆腔器官脱垂的细胞外基质代谢

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI: 10.1002/jbt.70358

Zexuan Zhou, Meixian Fang, Jiashou Luo, Xin Fan, Yong Zhao

{"title":"Klotho Regulates the Extracellular Matrix Metabolism via TGF-β1/Wnt Signaling Pathway of Fibroblasts in Pelvic Organ Prolapse","authors":"Zexuan Zhou, Meixian Fang, Jiashou Luo, Xin Fan, Yong Zhao","doi":"10.1002/jbt.70358","DOIUrl":"https://doi.org/10.1002/jbt.70358","url":null,"abstract":"<div>\u0000 \u0000 Pelvic organ prolapse (POP) is a gynecological disease frequently diagnosed in middle-aged and elderly women. Klotho is an antiaging protein. This study aimed to investigate the regulatory role and potential molecular mechanism of Klotho in the pathological process of POP. Random sampling was used to collect vaginal wall clinical samples from patients with POP (grade III or IV) and non-POP conditions (such as uterine fibroids and cervical precancerous lesions), with five cases in each group. Western blot was performed to detect the expression of Klotho and extracellular matrix (ECM) metabolism-related proteins. Primary fibroblasts were extracted and identified using immunocytochemistry. Fibroblast viability was assessed by MTT, and apoptosis levels were detected by flow cytometry. A POP fibroblast oxidative stress model was developed using H2O2, and qRT-PCR was utilized to determine the relative mRNA expression of Klotho. Klotho, Col-I, FN and CTGF proteins were low-expressed in POP patient samples, MMP2 protein was highly expressed in POP patient samples. After overexpression of Klotho, the expressions of Col-I, FN and CTGF proteins in fibroblasts were upregulated, the expressions of MMP2, β-catenin and TGF-β1 proteins were downregulated, the cell proliferation ability was increased, and the apoptosis level was reduced. However, the above results were reversed when further treated with the TGF-β1 signaling pathway activator SRI-011381. Klotho expression was suppressed by H2O2 treatment of POP fibroblasts. By regulating the TFG-β1/Wnt signaling pathway, Klotho affected ECM metabolism in POP fibroblasts to suppress the POP occurrence and development. Meanwhile, the expression of Klotho in POP fibroblasts could be affected by oxidative stress.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292489","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}

引用次数: 0

Studying the Toxicity of Trolox on Hepatocytes and Drug-Induced Liver Injury 曲洛克斯对肝细胞的毒性及药物性肝损伤的研究

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI: 10.1002/jbt.70359

Nidal A. Qinna, Ola N. Estatieh, Bayan Y. Ghanem, Eyad M. Mallah, Qasem Abdallah, Mohammad Ahmad

{"title":"Studying the Toxicity of Trolox on Hepatocytes and Drug-Induced Liver Injury","authors":"Nidal A. Qinna, Ola N. Estatieh, Bayan Y. Ghanem, Eyad M. Mallah, Qasem Abdallah, Mohammad Ahmad","doi":"10.1002/jbt.70359","DOIUrl":"https://doi.org/10.1002/jbt.70359","url":null,"abstract":"<div>\u0000 \u0000 The Vitamin E analogue Trolox (Tx) is a well-known reference compound utilized in various In Vitro antioxidant assays. In Vivo experimentation of the scavenging and protective potential of Tx is increasing, however, its impact on healthy and stressed models has not been thoroughly examined. The current study evaluates Tx under both In Vitro and In Vivo settings, employing the classical acetaminophen (APAP)-induced hepatotoxicity model to assess its ability to manage and prevent liver injury. Primary mouse hepatocytes and C57/B6 mice were treated with Tx either alone or before exposure to APAP. Cell modality and viability were evaluated In Vitro, along with In Vivo hepatic functions and histological changes. The mRNA levels of stress response and cell-death associated genes were analyzed in liver homogenates, along with the levels of NRF2 proteins, a crucial intracellular antioxidant regulator. The conducted experiments revealed that Tx (1 mM) reduced cell viability, triggered apoptosis, and led to DNA leakage in cells, while exacerbating injury when administered as a pretreatment before APAP exposure in mice. This damage was correlated with dose-dependent hemorrhagic necrosis observed in liver tissue sections and a dose-dependent increase in serum LDH. Tx affected the mRNA expression of CYP metabolism enzymes, as well as Sult1a1 expression and genes related to NRF2/ARE pathway. Furthermore, NRF2 activity was diminished following pretreatment with Tx doses. Despite its recognized antioxidant properties, Tx induced liver injury in a concentration-dependent manner in both normal and stressed liver models. Consequently, the use of Tx may pose injury that is evident and requires further investigation across various pathological models.</div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292485","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}

引用次数: 0

Cancer-Associated Fibroblast-Derived RIPK4 Confers Cisplatin Resistance in Gastric Cancer by Activating the PI3K/AKT Pathway 癌症相关成纤维细胞衍生的RIPK4通过激活PI3K/AKT通路赋予胃癌顺铂耐药

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-06-16 DOI: 10.1002/jbt.70320

Rui Chen, Junfang Dai, Bo Wang, Guofei Peng, Yao Xun, Yan Li

{"title":"Cancer-Associated Fibroblast-Derived RIPK4 Confers Cisplatin Resistance in Gastric Cancer by Activating the PI3K/AKT Pathway","authors":"Rui Chen, Junfang Dai, Bo Wang, Guofei Peng, Yao Xun, Yan Li","doi":"10.1002/jbt.70320","DOIUrl":"https://doi.org/10.1002/jbt.70320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 Cancer-associated fibroblasts (CAFs) play a central role in cancer progression and are involved in modulating cancer cell proliferation, invasion, metastasis, drug resistance and so on. Receptor Interacting Serine/Threonine Kinase 4 (RIPK4) was demonstrated to promote gastric cancer (GC) metastasis and tumorigenesis. Here, this study aimed to explore whether GC-derived CAFs affected cisplatin (DDP) resistance in GC cells via RIPK4. DDP-resistant GC cells were first established. Levels of RIPK4 mRNA and proteins were detected using qRT-PCR and western blotting. The IC50 values of DDP, cell proliferation, invasion, and migration were analyzed using MTT, 5-ethynyl-2′-deoxyuridine, transwell, and wound healing assays, respectively. PI3K/AKT pathway-related proteins were measured by western blotting. Animal experiments were performed for in vivo analysis. Here, we found that CAFs enhanced DDP resistance in DDP-resistant cells by promoting cell proliferation, invasion and migration. CAFs led to an increased RIPK4 expression in DDP-resistant cells. The silencing of RIPK4 suppressed DDP resistance in DDP-resistant cells. Moreover, RIPK4 silencing in CAFs could also reduce DDP resistance in GC. Mechanistically, CAFs could activate the PI3K/AKT pathway by RIPK4. In vivo assay also showed that RIPK4 silencing in CAFs attenuated CAF-induced DDP resistance. In conclusion, RIPK4-decreased CAFs suppressed DDP resistance in GC by blocking the activation of the PI3K/AKT pathway, recommending a novel method for overcoming DDP resistance in gastric cancer.\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292487","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}

引用次数: 0