Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Chitosan-Based Systems for Curcumin Delivery: Evidence for Therapeutic Applications","authors":"Mylene Martins Monteiro,&nbsp;Bruna Bastos Silveira,&nbsp;Larissa Di Carvalho Melo,&nbsp;Seila Tolentino,&nbsp;Juliana Amorim dos Santos,&nbsp;Elaine Barros Ferreira,&nbsp;Paula Elaine Diniz dos Reis,&nbsp;Guilherme M. Gelfuso,&nbsp;Eliete Neves Silva Guerra","doi":"10.1002/jbt.70515","DOIUrl":"10.1002/jbt.70515","url":null,"abstract":"<div>\u0000 \u0000 <p>Curcumin, a bioactive polyphenol from <i>Curcuma longa</i>, exhibits anti-inflammatory, antioxidant, and anticancer effects. Despite its therapeutic promise, curcumin's clinical use is limited by poor water solubility and low bioavailability. Chitosan-based delivery systems, especially polymeric nanoparticles, have been a strategy to improve curcumin's solubility, stability, and provide targeted drug delivery. This review maps evidence on the use of delivery systems based on the natural polymer chitosan incorporating curcumin for disease management, highlighting their potential to enhance therapeutic outcomes. The review included studies involving humans, animals, or cell cultures using chitosan-based systems for curcumin delivery for therapeutical purposes. A systematic search was performed in PubMed, EMBASE, Web of Science Core Collection, and Google Scholar (January 16, 2025). Two independent reviewers selected studies, and data were synthesized descriptively. Bibliometric analysis was conducted using VOSviewer. From 5336 records, 387 studies met inclusion criteria. Cancer (212 studies) and wound healing (112 studies) were the predominant topics. Co-occurrence analysis revealed curcumin, chitosan, and drug delivery as the main reported keywords. In cancer treatment, compiled evidence from in vitro and animal suggests that chitosan-based nanoparticles enhanced curcumin's bioavailability, cytotoxicity, and therapeutic effect. The treatment was often applied in synergy with agents like 5-fluorouracil, methotrexate, and paclitaxel. In wound healing, hydrogels, scaffolds, nanofibers, and films improved biocompatibility, antibacterial properties, and regenerative capacity, especially for diabetic wounds and burns. In some cases, the treatment incorporated other bioactives like EGF, exosomes, or aloe vera. Chitosan-based formulations containing curcumin have demonstrated strong potential in cancer treatment and wound healing care.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137601","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":"Exosome Carrying OCT4/miR-1246/β-catenin Deriving From HBV Infected Hepatocytes Accelerated Liver Fibrosis","authors":"Tiantian Zhu,&nbsp;Yuankun Chen,&nbsp;Mingyue Niu,&nbsp;Qionghan He,&nbsp;Minhua Weng,&nbsp;Zheng Wang,&nbsp;Wenting Li","doi":"10.1002/jbt.70521","DOIUrl":"10.1002/jbt.70521","url":null,"abstract":"<div>\u0000 \u0000 <p>Accumulating research highlights the critical involvement of octamer-binding transcription factor 4 (OCT4) in liver fibrosis (LF) development. However, the mechanistic relationship between OCT4 and hepatitis B virus (HBV)-associated LF remains unclear. HBV exposure markedly upregulated OCT4 and miR-1246 expression in both HepAD38 and HepG2-NTCP cell lines. These effects were reversed by entecavir treatment or the Hepatitis B X (HBx) knockdown. Furthermore, overexpression of OCT4 enhanced expression of miR-1246, β-catenin, and LF-associated genes in LX2 (Hepatic stellate cell) cells. Interestingly, exosomes from HBV infected HepG2-NTCP cells upregulated OCT4/miR-1246/β-catenin expression as well as α-SMA, Col1A and TIMP-1 in LX2 cells. These fibrogenic effects were inhibited by HBx gRNA. Moreover, 26 HBV infected patients were enrolled in this study. The expression of miR-1246 and β-catenin in liver tissue were strongly correlated with LF. These results showed that HBV induced LF through exosomal OCT4/miR-1246/β-catenin Pathway, which lay a basis for LF treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137640","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":"Ferroptosis and Lipid Peroxidation Participate in Valproic Acid-Induced Hepatotoxicity via the Long-chain Acyl-CoA Synthetase 4/Glutathione Peroxidase 4 Pathway","authors":"Ying Zhang,&nbsp;Tong Li,&nbsp;Yujia Zhang,&nbsp;Tianyu Xu,&nbsp;Limei Zhao","doi":"10.1002/jbt.70484","DOIUrl":"10.1002/jbt.70484","url":null,"abstract":"<div>\u0000 \u0000 <p>Valproic acid (VPA) is a commonly prescribed antiepileptic drug, with hepatotoxicity being one of its most frequent and severe adverse effects. The underlying mechanisms of VPA-induced hepatotoxicity remain elusive. Thus, this study aimed to investigate the involvement of ferroptosis in VPA-induced hepatotoxicity in vivo and in vitro. C57BL/6 J mice and HepG2 cells were treated with VPA to establish VPA-induced hepatotoxic models. The results demonstrated that VPA not only induced hepatic steatosis but also elevated liver biochemical and oxidative stress indicators, suggesting that VPA-induced hepatotoxicity affects hepatic iron metabolism. Moreover, VPA treatment altered the expression of ferroptosis-related proteins and lipid peroxides, indicating that ferroptosis contributed to VPA-induced hepatotoxicity. To investigate the role of ACSL4, a pivotal enzyme in lipid peroxidation during ferroptosis, in VPA-induced hepatotoxicity, a study was conducted utilizing rosiglitazone (RSG), a specific inhibitor of ACSL4, to interfere with the overexpression of ACSL4 in a model mouse system. Furthermore, an in vitro approach was employed, where ACSL4 siRNA was utilized to knock down ACSL4 expression in a cellular model of VPA-induced hepatotoxicity. This dual-pronged strategy aimed at elucidating the mechanistic contributions of ACSL4 in mediating the deleterious effects of VPA on the liver. In summary, ferroptosis emerges as a novel mechanism underlying VPA-induced hepatotoxicity, and ACSL4 may serve as a crucial target in the process of VPA-induced liver injury. This study has the potential to lay the groundwork for the development of novel therapeutic strategies for treating VPA-induced liver damage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130904","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":"Anticancer Potential of Antimicrobial Peptides: Focus on Breast Cancer","authors":"Wen Yang,&nbsp;Hongyan Hou,&nbsp;Ran Chai,&nbsp;Jiaxiang Guo","doi":"10.1002/jbt.70525","DOIUrl":"10.1002/jbt.70525","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer impacts millions globally, with a significant annual rise in the incidence of new cases. Although considerable progress has been made in cancer therapies and numerous options exist to address this disease, the overall survival rates for individuals with breast cancer remain distinctly low. This situation is attributed to the emergence of resistance against chemotherapeutic agents used for breast cancer, along with the inadequate characteristics of the existing generation of oncological medications. Therefore, there is an imperative necessity for the creation of innovative treatments that exhibit minimal adverse effects, enhanced properties, and the absence of drug resistance. A noteworthy development in this field is the exploration of antimicrobial peptides (AMPs), which are natural constituents of the innate immune system, as a novel class of anticancer therapeutics. AMPs display multiple advantageous traits that make them attractive candidates for cancer therapy. In this review, we will review recent research focused on the application of AMPs in breast cancer therapy and determine their mechanisms of action. We will also investigate the potential of combining AMP-based treatments with existing breast cancer management approaches. This study highlights the promising potential of AMPs as a novel approach to treating breast cancer, providing promise for less harmful and more efficient therapies.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130922","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":"Assessment of the Toxic Effect of Zinc Oxide Nanoparticles on Brain, Kidney and Spleen of Adult Male Albino Rats and Possible Protective Role of Copper (II) Albumin Complex","authors":"Asmaa H. M. Soliman,&nbsp;Amany M. Ismaiel,&nbsp;Zainab S. Abdelqader,&nbsp;Doaa Almaz","doi":"10.1002/jbt.70530","DOIUrl":"10.1002/jbt.70530","url":null,"abstract":"<div>\u0000 \u0000 <p>The present study aimed to assess the toxic effect of sub chronic administration of zinc oxide nanoparticles (ZnO-NPs) on brain, kidney and spleen of adult male rats and to assess the possible protective role of copper (II) albumin complex. (40) Rats were randomly divided into four equal groups and were treated once daily for 30 days as follow: Group I (control): (five received a regular diet and tap water and the others received 1 mL/day of milk (solvent of Cu (II) albumin complex) in addition to regular diet and tap water. Group II: received copper (II) albumin complex dissolved in milk (1 mL/day). Group III: received (400 mg/kg/day) of (ZnO-NPs). Group VI: received copper (II) albumin complex and ZnO-NPs (400 mg/kg/day). At the end of the experiment, blood samples were collected for kidney function tests and animals were euthanized for collection of organs for histopathology and immunohistochemistry. ZnO-NPs induced significant distribution of cellular and nuclear integrity, inflammatory and degenerative changes in the brain, kidney and spleen. Immunohistochemical staining showed a strong positive immunoreactivity with caspase 3 antibody. Moreover, significant increase in blood urea and serum creatinine levels were also noticed. The study group that received copper (II) albumin showed significant improvement in the toxic structural changes induced by ZnO-NPs with observed regeneration and restoration of normal histological structures and significantly reduced blood urea and creatinine levels. The Cu-II-Album complex is an effective protective agent against ZnO-NPs induced toxicity as indicated by maintaining histology of the studied organs and the renal functions.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130909","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":"miR-140-3p Alleviates Pulmonary Arterial Smooth Muscle Cell Dysfunction via MAP2K6/p38 Pathway","authors":"Ling Chen,&nbsp;Jia-Yi Zhang,&nbsp;Lei Huang,&nbsp;Lin-Ling Jin,&nbsp;Wei-Ping Xie,&nbsp;Hong Wang,&nbsp;Meng-Yu He,&nbsp;Hui Kong","doi":"10.1002/jbt.70532","DOIUrl":"10.1002/jbt.70532","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling arising from aberrant proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Recent studies indicate that miR-140-3p plays a significant role in cell proliferation and apoptosis. However, whether miR-140-3p involves in the development of PAH remains unknown. In this study, we showed that the expressions of miR-140-3p in SU5416/hypoxia (SuHx)-induced PAH and hypoxia-treated human PASMCs were significantly downregulated. Administration of the rno-miR-140-3p agomir significantly alleviated right ventricular systolic pressure, pulmonary vascular remodeling, and right ventricular hypertrophy in PAH. In cultured PASMCs, transfected with miR-140-3p mimics effectively inhibited hypoxia-induced cell proliferation and migration, while facilitated cell apoptosis. Conversely, suppression of miR-140-3p activity by its inhibitors exerted the opposite effects. Dual-luciferase reporter assay showed that miR-140-3p targeted the 3′-UTR of the mRNA of MAP2K6, thus decreased transcripts and its protein expression, and thereafter inhibited the phosphorylation activation of p38. Moreover, upregulation of MAP2K6 counteracted the inhibitory effect of miR-140-3p on matrix metalloproteinase 2/9 (MMP2/9) expression and pro-apoptotic effects as indicated by Bcl2/BAX in hypoxia-treated human PASMCs. Collectively, our findings highlighted the therapeutic potential of miR-140-3p in PAH and revealed a regulatory mechanism involving the miR-140-3p/MAP2K6/p38 axis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124534","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":"Toxicological Assessment of Microplastics in Zebrafish: Biochemical Responses and Histopathological Changes","authors":"Immaculate J.K.,&nbsp;Narmatha S.M.,&nbsp;Jamila P.","doi":"10.1002/jbt.70518","DOIUrl":"10.1002/jbt.70518","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigated the effects of polyethylene microplastics (PE MPs) on zebrafish (<i>Danio Rerio</i>), focusing on their survival, growth, bioaccumulation, oxidative stress and histopathological changes. Zebrafish were treated with two sizes of PE MPs (50 and 100 µm) at concentrations of 0.1, 10, 50, and 500 μg L⁻¹ for 12 and 24 days. Survival rates were high (&gt; 95%), with no significant effect on growth. Bioaccumulation of MPs was dose dependent, with higher retention in the liver and gut than in the gills. The smaller MPs (50 µm) dispersed more widely in the body, whereas the larger MPs (100 µm) were mostly retained in the digestive organs. Oxidative stress responses, indicated by increased activity of enzymatic antioxidants such as superoxide dismutase (SOD) and catalase (CAT), along with elevated levels of nonenzymatic antioxidants including glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px), were observed with higher concentrations and longer exposure periods. Elevated lipid peroxidation (LPO) levels suggested cellular damage due to oxidative imbalance. Histopathological investigation showed concentration-dependent structural damage in the intestinal epithelial cells with necrosis, infiltration, and lipid droplet formation in the hepatocytes, while there was minimal or no damage to the brain and kidney. These findings demonstrate that exposure to MPs can induce bioaccumulation and oxidative stress in aquatic organisms, highlighting the need for mitigation strategies and further research into the long-term ecological impacts of MPs in aquatic ecosystems.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124549","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":"Melatonin Mitigates Abamectin-Induced Subacute Hematotoxicity and Hepato-Renal Toxicity in Rats by Regulating Oxidative Stress, Inflammatory Responses, and Apoptosis","authors":"Hatice Karaboduk,&nbsp;Caglar Adiguzel,&nbsp;Meltem Uzunhisarcikli,&nbsp;Fatma Gokce Apaydin,&nbsp;Yusuf Kalender","doi":"10.1002/jbt.70512","DOIUrl":"https://doi.org/10.1002/jbt.70512","url":null,"abstract":"<div>\u0000 \u0000 <p>Abamectin is a widely used pesticide due to its strong anthelmintic and insecticidal activity and has toxic effects on nontarget organisms. In this study, melatonin (10 mg/kg body weight), which has potent anti-inflammatory, antiapoptotic, and antioxidant effects against subacute hepato-renal toxicity of abamectin (0.5 mg/kg body weight) in rats, was evaluated for its potential to alleviate organ damage by biochemical, oxidative stress, immunohistochemical, histopathological, and cytopathological studies. In hepato-renal tissues of abamectin-treated rats, MDA and 8-OHdG levels, total oxidant status, and oxidative stress index significantly increased. In contrast, endogenous antioxidant enzyme activities and total antioxidant status decreased significantly. A significant decrease in acetylcholinesterase activity, TNF-α and caspase-3 immunopositive cells, and interleukin-17 levels were also detected in the tissues. Abamectin caused a substantial reduction in red blood cell, hemoglobin, hematocrit, and platelet counts and significantly increased white blood cell count. In addition, abamectin increased the activities of ALT, AST, ALP, and LDH, and the levels of total cholesterol, triglyceride, creatinine, uric acid, urea, and BUN, which are evaluated as biomarkers of blood hepato-renal tissues. At the same time, it caused a decrease in the levels of total protein and albumin. In addition, these changing biochemical parameters are accompanied by cytopathological and histopathological changes in hepato-renal tissues. However, exogenous melatonin supplementation reduced the oxidative stress caused by abamectin in rats and caused the pathological changes in hepato-renal tissues to be observed more mildly. It also reversed the changes in blood parameters and hepato-renal markers. In conclusion, this study suggests that exogenous melatonin supplementation may help significantly ameliorate abamectin-induced hepato-renal injury in rats through anti-inflammatory, antioxidant, and antiapoptotic mechanisms.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110686","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":"Exosome-Derived lncRNA LIPE-AS1 Enhances Oocytes Maturation and Ameliorates Diminished Ovarian Reserve via the miR-330-5p/HDAC3 Axis","authors":"Jialing Li,&nbsp;Hua Guo,&nbsp;Miaomiao Tian,&nbsp;Feimiao Wang,&nbsp;Jinmei Gao,&nbsp;Lu Wang,&nbsp;Jie Ma,&nbsp;Rong Hu","doi":"10.1002/jbt.70519","DOIUrl":"https://doi.org/10.1002/jbt.70519","url":null,"abstract":"<div>\u0000 \u0000 <p>Diminished ovarian reserve (DOR) is a multifactorial gynecological disorder that has emerged as a significant global health challenge. Currently, there are no effective preventive or therapeutic strategies for DOR. Exosome-derived long non-coding RNAs (lncRNA) in follicular fluid (FF) plays a crucial role in follicular development. We identified exosome-derived lncRNA LIPE-AS1 from the FF of DOR patients, which regulates histone deacetylase 3 (HDAC3) expression by competitively binding to miR-330-5p. Exosomes, as nanosized membrane vesicles, can deliver therapeutic agents in a targeted manner through ligand modification. In this study, we employed engineered exosomes combined with lncRNA for ovary-targeted therapy of DOR. First, we elucidated the role of lncRNA LIPE-AS1 in the pathogenesis of DOR. Next, we generated exosomes with high LIPE-AS1 expression (Exo-LIPE-AS1) using 293 T cells. Co-culture of Exo-LIPE-AS1 with oocytes from DOR models enhanced oocyte maturation and improve oocyte quality in vitro. Finally, we developed FSHβ-modified, LIPE-AS1-loaded exosomes (Exo_FSHβ-LIPE-AS1), which demonstrated enhanced ovarian delivery efficiency in vivo. Consequently, Exo_FSHβ-LIPE-AS1improved fertility outcomes in DOR models. Our findings demonstrate that exosomes serve as effective targeted vehicles for lncRNA LIPE-AS1, offering potential preventive and therapeutic benefits for DOR.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110684","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":"Ketamine Induces Mitochondrial Fission and Dysfunction in Cervical Cancer Cells via RhoA-Dependent DRP-1 Activation","authors":"Yanfang Zhou,&nbsp;Guangming Chen,&nbsp;Ye Zhu","doi":"10.1002/jbt.70500","DOIUrl":"https://doi.org/10.1002/jbt.70500","url":null,"abstract":"<div>\u0000 \u0000 <p>Mitochondrial fragmentation, which is closely linked to mitochondrial dysfunction, has emerged as a critical treatment target for cervical cancer. Ketamine, a well-known anesthetic, has shown potential in cancer therapy by inducing cytotoxicity, impairing mitochondrial function, and promoting apoptosis in tumor cells. Notably, the regulatory role of ketamine in mitochondrial network dynamics remains unexplored in current scientific literature. In this study, we demonstrated that ketamine exerts significant cytotoxic effects on C33A cervical cancer cells, as evidenced by dose-dependent increases in γ-glutamyl transpeptidase (GGT) levels and lactate dehydrogenase (LDH) release, accompanied by a corresponding reduction in cell viability. At 100 μM, ketamine induces mitochondrial dysfunction, characterized by decreased Complex IV activity, mitochondrial membrane potential (MMP), and ATP production, along with mitochondrial fragmentation. Mechanistically, ketamine upregulates mitochondrial p-Drp1 levels without altering total DRP-1 and enhances the expression of CaMK II and RhoA, but not Rac1/Cdc42. Inhibition of RhoA, but not CaMK II, attenuates ketamine-induced mitochondrial DRP-1 activation, fragmentation, and dysfunction, suggesting that RhoA is a key mediator. These findings highlight ketamine's potential as a therapeutic agent targeting mitochondrial dynamics in cervical cancer.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110685","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}