Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Exosomal Dialogue: The Emerging Role of Cancer-Associated Fibroblast-Derived Exosomes in Colorectal Cancer Progression and Therapy Resistance","authors":"Ahmed Hjazi,&nbsp;Raed Obaid Saleh,&nbsp;Zahraa Abbas Al-Khafaji,&nbsp;Ali G. Alkhathami,&nbsp; Malathi.H,&nbsp;Mayank Kundlas,&nbsp;Laxmidhar Maharana,&nbsp;Ashish Singh Chauhan,&nbsp;Yasser Fakri Mustafa,&nbsp;Hamza Fadhel Hamzah","doi":"10.1002/jbt.70780","DOIUrl":"10.1002/jbt.70780","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) remains a significant global health burden, being the third most diagnosed cancer and second leading cause of cancer-related mortality. While there have been advances in early detection and treatment of CRC, outcomes for patients with advanced or metastatic disease remain poor due to high rates of therapy resistance and disease recurrence. Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of CRC by actively modulating the tumor microenvironment (TME). CAFs differ from normal fibroblasts in that they remain persistently activated and acquire a myofibroblast-type behavior due to various signaling pathways, including transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and interleukins in CRC. One of the most important ways that CAFs mediate their pro-tumorigenic effect is through the release of exosomes. Exosomes are small extracellular vesicles that carry a broad range of cargo, including proteins, lipids, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and metabolites. These CAF-derived exosomes contribute to robust intercellular communication within the tumor microenvironment (TME), reprogramming both cancer cells and the remaining stromal elements. Also, particular emphasis is placed on how CAF-derived exosomes modulate cellular responses to cytotoxic agents, containing 5-fluorouracil, oxaliplatin, irinotecan, and radiotherapy. These exosomes alter DNA damage responses, ferroptosis, apoptosis, oxidative stress, and survival signaling, thereby reshaping the toxicity profile of anticancer treatments. Understanding these exosome-mediated mechanisms is critical for overcoming chemoresistance and radiosurvival in CRC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512340","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":"USP32 Promotes Cancer Cell Invasion, Macrophage M2 Polarization, and CD8+ T Cell Apoptosis in Gastric Cancer Through Upregulation of DAPK1","authors":"Weitao Zhang,&nbsp;Zhi Zheng,&nbsp;Jun Li,&nbsp;Xiaoyun Dai,&nbsp;Jin Wang","doi":"10.1002/jbt.70792","DOIUrl":"10.1002/jbt.70792","url":null,"abstract":"<div>\u0000 \u0000 <p>M2-like macrophages and CD8+T cells are key immune components that influence tumor behavior and treatment response. Ubiquitin-specific protease 32 (USP32) is established as a key oncogenic factor in gastric cancer (GC). This study aimed to investigate the role of USP32 in regulating M2 macrophage polarization and CD8+T cell dysfunction in GC. Macrophages derived from THP1 cells (THP1-M0) or CD8+T cells were co-cultured with transfected AGS and HGC-27 GC cells. The proportion of CD206⁺ M2 macrophages and the apoptosis of CD8+T cells were assessed by flow cytometry. Cell invasion was analyzed by transwell assay. The interaction between USP32 and death-associated protein kinase 1 (DAPK1) was verified by GST pull down and Co-immunoprecipitation (Co-IP) experiments. The effect on tumor growth was tested by subcutaneous xenograft studies. USP32 and DAPK1 were overexpressed in GC tissues and cell lines. Mechanistically, USP32 stabilized DAPK1 protein through deubiquitination. DAPK1 downregulation reversed USP32-mediated enhancement in GC cell invasion, macrophage M2 polarization, and CD8+T cell apoptosis in vitro. USP32 depletion exhibited an in vivo anti-growth effect on AGS subcutaneous xenografts. This study identifies the USP32/DAPK1 cascade as a crucial regulator of M2 macrophage polarization and CD8+T cell apoptosis in GC, providing a novel mechanistic link between post-translational regulation and tumor immune evasion.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512384","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":"Foodborne Mycotoxins as Molecular and Epigenetic Carcinogens: Biochemical Mechanisms and Toxicological Implications","authors":"Smita Kumari,&nbsp;Jyotsna Misra,&nbsp;Niraj Kumar Jha,&nbsp;Naveen Kumar,&nbsp;Karthikeyan Ravi,&nbsp;Rohan Gupta","doi":"10.1002/jbt.70794","DOIUrl":"10.1002/jbt.70794","url":null,"abstract":"<div>\u0000 \u0000 <p>Mycotoxins are toxic secondary metabolites produced predominantly by fungal genera, such as <i>Aspergillus</i>, <i>Fusarium</i>, and <i>Penicillium</i>, and represent major foodborne contaminants responsible for chronic human exposure worldwide. While aflatoxin B1 (AFB1) is a well-established hepatocarcinogen, increasing evidence indicates that multiple mycotoxins contribute to tumorigenesis across diverse organ systems through shared biochemical and molecular mechanisms. At the molecular level, mycotoxins undergo cytochrome P450–mediated bioactivation, generating reactive intermediates that induce DNA adduct formation, oxidative stress, genomic instability, and disruption of redox homeostasis. These events converge on dysregulation of key signaling pathways governing cell-cycle control, apoptosis, immune surveillance, and epigenetic regulation, including aberrant DNA methylation, histone modification, and non-coding RNA expression. Importantly, emerging data support a “dual-hit” paradigm in which mycotoxin exposure synergizes with oncogenic viral infections, such as hepatitis B virus (HBV), human papillomavirus (HPV), and Epstein-Barr virus (EBV), amplifying genotoxic stress, immune evasion, and epigenetic instability. This review synthesizes current mechanistic insights into mycotoxin-induced carcinogenesis, emphasizing molecular toxicological endpoints that link exposure to cancer risk. In addition, advances in biosensing, detoxification, and preventive strategies are discussed, highlighting the need for mechanism-driven interventions to mitigate mycotoxin-associated carcinogenicity and its public health burden.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512320","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":"Ononin Inhibits the Growth and Metastasis of Hepatocellular Carcinoma by Suppressing MMP-2 and MMP-9 via PI3K/AKT/mTOR Signaling","authors":"Shasha Peng,&nbsp;Jun Guo,&nbsp;Hongfei Fu","doi":"10.1002/jbt.70804","DOIUrl":"10.1002/jbt.70804","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, which is difficult to control with conventional surgical and chemotherapeutic approaches owing to distant metastasis. Therefore, alternative medicines with high efficacy but minimal side effects are urgently needed. Recently, increasing evidence has demonstrated that ononin, an isoflavone glycoside widely distributed in herbs and food plants, exhibits potent anticancer effects across various cancers. Our research aimed to determine the influence of ononin on HCC growth and metastasis and identify the potential mechanism of action. The anti-proliferative and anti-metastatic properties of ononin in human HCC cells were determined using MTT, colony formation, flow cytometry, wound-healing, and Transwell assays. The expression of cell cycle-related proteins, matrix metalloproteinases (MMP-2 and MMP-9), and PI3K/AKT/mTOR pathway-related molecules in HCC cells was examined by western blotting. TGF-β1 or the PI3K activator 740Y-P was used for combined cell treatment with ononin to validate the effects of ononin on TGF-β1-triggered HCC cell metastasis and the role of the PI3K/AKT/mTOR pathway in ononin's anticancer effects. The in vivo therapeutic effects were finally validated in xenograft mouse models. Ononin suppressed HCC cell growth, induced G0/G1 cell cycle arrest, and reduced CDK6, cyclin D1, and CDK4 protein levels in HCC cells. Ononin inhibited HCC cell migration and invasion and downregulated MMP-2/9 expression with or without TGF-β1 stimulation. Ononin attenuated p-PI3K, p-AKT, and p-mTOR protein levels in HCC cells, and 740Y-P abolished the repression of ononin on HCC cell growth and metastasis. Additionally, ononin restricted tumor growth, decreased Ki67 and p-AKT expression, and curbed lung metastasis in xenograft mouse models. Ononin inhibits HCC growth and metastasis by downregulating MMP-2 and MMP-9 through inactivating the PI3K/AKT/mTOR signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512285","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":"NUPR1 and LCN2: Potential Therapeutic Targets for Colorectal Cancer Via Modulating Cell Viability, Migration, and Ferroptosis-Related Pathways","authors":"Danni Luo,&nbsp;Xiaopan Luo,&nbsp;Shaojie Qian,&nbsp;Jintao Liu","doi":"10.1002/jbt.70809","DOIUrl":"10.1002/jbt.70809","url":null,"abstract":"<div>\u0000 \u0000 <p>Nuclear protein 1 (NUPR1) is a small, highly basic transcriptional regulator that is involved in regulating a variety of cellular processes. However, its role in colorectal cancer (CRC) remains uncertain. This study aimed to elucidate the NUPR1 role in CRC progression and to explore its downstream mechanism. Cell viability, migration and invasive capabilities were detected using cell counting kit-8 and Transwell assays. The Iron content, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and lipid peroxidation were measured using assay kits. The interaction between NUPR1 and lipocalin 2 (LCN2) was examined by co-immunoprecipitation (Co-IP) and dual-luciferase reporter assays. BALB/c nude mice were used to establish xenograft models, tumor weight and volume were systematically recorded. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to quantify gene expression levels in both cellular and tumor tissue samples. Our results indicated that NUPR1 and LCN2 were significantly overexpressed in CRC cell lines. NUPR1 and LCN2 knockdown led to a significant reduction in cell viability and a decrease in both migratory and invasive capacity. The effects of NUPR1 knockdown on GSH, ROS, lipid peroxidation, iron, and MDA levels were comparable to those observed after erastin treatment. Moreover, the administration of ferrostatin-1 partially alleviated the effects of NUPR1 overexpression. Dual-luciferase reporter and Co-IP assays have demonstrated a direct interaction between NUPR1 and LCN2. In vivo experiments indicated that NUPR1 and LCN2 knockdown inhibited tumor growth, whereas NUPR1 overexpression facilitated tumor progression. NUPR1 and LCN2 knockdown resulted in increased acyl-CoA synthetase long-chain family member 4 (ACSL4) levels and a decrease in glutathione peroxidase 4 (GPX4) expression. Notably, the effects of NUPR1 overexpression were partially reversed by the LCN2 knockdown. These findings suggest a significant association between NUPR1 and LCN2, indicating that NUPR1 may serve as a potential therapeutic target for CRC treatment.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504010","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: Vitamin D3 Exerts a Neuroprotective Effect in Metabolic Syndrome Rats: Role of BDNF/TRKB/Akt/GS3Kβ Pathway","authors":"","doi":"10.1002/jbt.70796","DOIUrl":"10.1002/jbt.70796","url":null,"abstract":"<p><b>RETRACTION</b>: N. Aladdin and S. A. Ghareib, “Vitamin D3 Exerts a Neuroprotective Effect in Metabolic Syndrome Rats: Role of BDNF/TRKB/Akt/GS3Kβ Pathway,” <i>Journal of Biochemical and Molecular Toxicology</i> 38, no. 12 (2024): e70082, https://doi.org/10.1002/jbt.70082.</p><p>The above article, published online on 09 December 2024 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 upon following concerns raised by a third party regarding data reuse between this article and two other articles previously published elsewhere by the same authors. An investigation confirmed that there are substantial overlaps among the three papers. The authors provided some supporting data and explained that the three studies were related, and that data from a limited number of animals were shared to confirm the disease model. However, analysis of the data showed that the overlaps were not restricted to disease model validation. The editors have therefore lost confidence in the results presented in this article and consider the conclusions to be invalid. The authors disagree with the retraction.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503952","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":"Geraniol Mitigates Cytarabine-Induced Hepatotoxicity in Mice via PI3K/AKT-Mediated NRF2 Activation","authors":"Rebai Ben Ammar,&nbsp;Peramaiyan Rajendran,&nbsp;Sarah Abdulaziz Alamer,&nbsp;Duaa Althumairy,&nbsp;Mayyadah Abdullah Alkuwayti","doi":"10.1002/jbt.70820","DOIUrl":"10.1002/jbt.70820","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatotoxicity, principally driven by oxidative stress and inflammation, is a notable adverse effect of cytarabine, a chemotherapeutic drug extensively utilized in cancer therapy. This research examines the hepatoprotective properties of the natural monoterpenoid geraniol (GNL) in a murine model of cytarabine-induced hepatic injury, emphasizing its influence on oxidative stress, inflammation, and critical signaling pathways like PI3K/AKT and NF-κB. The animals were categorized into four groups (<i>n</i> = 6). Groups II and III were administered cytarabine at a dosage of 0.3 mg/kg (i.p.) for a duration of 7 days. Group III received a pre-treatment of GNL (20 mg/kg) via intraperitoneal injection for 7 days prior to administration of cytarabine. Group IV was administered GNL only at a dosage of 20 mg/kg for 7 days. Group I served as a control. Cytarabine administration led to increased liver damage markers, including elevated blood ALT and AST levels, alongside heightened oxidative stress as seen by increased malondialdehyde (MDA) levels and diminished antioxidant enzyme activity (SOD and CAT). Moreover, cytarabine-induced inflammation was marked by elevated levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and the activation of the NF-κB signaling pathway, evidenced by enhanced nuclear translocation of p65. GNL therapy markedly alleviated these effects, lowering blood ALT and AST levels while reestablishing antioxidant equilibrium by diminishing MDA levels and augmenting SOD and CAT activity. Histopathological examination demonstrated significant improvement in liver tissue structure, characterized by reduced hepatocyte degradation and inflammatory infiltration. GNL suppressed NF-κB activation while promoting PI3K/AKT signaling, resulting in decreased pro-inflammatory cytokines and less liver damage. These findings underscore the potential of GNL as a hepatoprotective drug against cytarabine-induced hepatotoxicity, mediated by its antioxidant and anti-inflammatory effects through modulation of the PI3K/AKT and NF-κB pathways. Future research should investigate its therapeutic potential in alleviating chemotherapy-induced liver damage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503944","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":"Insights Into the Inhibitory Effect of Ofloxacin on Pepsin Through Peptidomics and Bioinformatics Approaches","authors":"Ran Yu,&nbsp;Rong Shen,&nbsp;Liang Chen,&nbsp;Peng Li","doi":"10.1002/jbt.70788","DOIUrl":"10.1002/jbt.70788","url":null,"abstract":"<div>\u0000 \u0000 <p>The hydrolysis of proteins by pepsin is of great significance for the biological utilization of proteins and the discovery of functional peptide molecules. Bovine serum albumin (BSA) and bovine collagen I (BCI) are both commonly used natural source proteins for studying the hydrolysis characteristics of pepsin. UHPLC − MS/MS, peptidomics, and molecular docking technologies were employed to investigate the underlying mechanism responsible for the inhibitory effect of ofloxacin on pepsin. The molecular weight distribution of peptides produced by pepsin in this study was mostly in the range of 600 Da to 1800 Da, and peptide segments were mostly composed of 9−11 amino acids. The predominant terminal amino acids were proline, glycine, leucine, valine, serine, and threonine. Ofloxacin led to conformational changes of the hydrolysis active sites of pepsin by forming hydrogen bonds with aspartic acids. When the key aspartic acid residues in the active center of pepsin were inhibited, the numbers of peptides TPAQD, VSVDAA, TVLFD, and TVIFD were upregulated. The hydrolysis characteristics of pepsin were changed, shown as an increase in the proportion of low molecular weight peptides and a decrease in the hydrophobicity of peptide segments in the hydrolysates. The study contributed to the evaluation of the activity of peptides from homologous protein hydrolysis by pepsin and the elucidation of the inhibitory mechanism of ofloxacin on pepsin.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498866","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":"Pindolol Mitigates Cancer Cachexia by Modulating Inflammation, Lipolysis, and Muscle Atrophy","authors":"Mit Joshi,&nbsp;Bhoomika M. Patel","doi":"10.1002/jbt.70812","DOIUrl":"10.1002/jbt.70812","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer cachexia is a complex syndrome associated with chronic inflammation, catabolic dysregulation, and sympathetic nervous system hyperactivity contribute to energy imbalance and skeletal muscle and adipose tissue wasting. This study investigates the therapeutic potential of pindolol in a murine model of cancer cachexia. In vitro study evaluated the cachexia-inducing potential of B16F10 melanoma cells and the therapeutic effects of pindolol on 3T3-L1 adipocytes. In vivo, cachexia was induced in male C57BL/6 mice via subcutaneous B16F10 melanoma cell injection, followed by pindolol treatment until the tumor volume reached 5000 mm³. Body weight, food intake, inflammatory markers, muscle and adipose tissue mass, adipokine levels, metabolic markers, organ weights, and gene expression of E3 ubiquitin-protein ligase TRIM63, Muscle Atrophy F-box gene (atrogin-1), and hormone sensitive lipase (HSL) were assessed. B16F10-conditioned media along with isoproterenol induced lipolysis in 3T3-L1 adipocytes, while pindolol reversed this effect. In vivo, pindolol significantly improved body weight, food intake, and systemic inflammation while restoring adipokine levels. Pindolol also preserved skeletal muscle and adipose depots, improved glucose levels, enhanced insulin sensitivity, and lowered triglycerides and cholesterol. Histological analysis confirmed muscle and adipose tissue preservation. Pindolol downregulated TRIM63 and Atrogin-1, reducing muscle atrophy, and decreased HSL, suggesting reduced lipolysis evident from mRNA expression. Pindolol alleviates cancer cachexia by reducing inflammation, preserving muscle and adipose mass, and improving metabolic parameters, highlighting its potential as a therapeutic candidate.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498918","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":"Protective Effect of Naringenin on Cadmium-Induced Kidney Injury in Rats","authors":"Hao Ling,&nbsp;Junbing Mao,&nbsp;Bing Xu,&nbsp;Yaning Shi,&nbsp;Jicang Wang","doi":"10.1002/jbt.70781","DOIUrl":"10.1002/jbt.70781","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium (Cd) exposure in occupational settings poses significant nephrotoxic risks, yet effective preventive strategies remain limited. This study investigated the protective effects of Naringenin (Nar) against Cd-induced nephrotoxicity. Twenty-four male SD rats (4 weeks old) were randomly assigned to control group, Cd group, Nar group, and Cd+ group for 14 days. Histopathological damage characterized by tubular necrosis and inflammatory infiltration. Cd exposure significantly impaired renal function, as evidenced by elevated serum uric acid and creatinine levels, increased oxidative stress markers (renal glutathione and malondialdehyde accumulation). Molecular analysis confirmed Cd-induced apoptosis through dysregulation of key apoptotic markers: downregulation of anti-apoptotic Bcl-2 and upregulation of pro-apoptotic Bax at both mRNA and protein levels, accompanied by increased cytochrome c release and activation of Caspase-9 and Caspase-3. These findings were further supported by TUNEL staining, which showed increased apoptosis in renal tubular cells. This study supports the potential application of naringin in alleviating cadmium-induced nephrotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468123","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}