Chemico-Biological Interactions最新文献

{"title":"Resveratrol-induced alterations in selected electrokinetic properties of in vitro models: LN-18 glioma cells and PC liposomes","authors":"Joanna Kotyńska ,&nbsp;Agnieszka Owerczuk ,&nbsp;Monika Naumowicz","doi":"10.1016/j.cbi.2026.111933","DOIUrl":"10.1016/j.cbi.2026.111933","url":null,"abstract":"<div><div>Resveratrol (RSV) has received widespread attention due to its diverse biological activities, including antioxidant, cardioprotective, and antitumor. Numerous preclinical investigations have revealed the anticancer action of resveratrol in various tumor types, including gliomas. This polyphenol is characterized by low water solubility and a high membrane partition coefficient, suggesting a strong affinity for the lipid components of biomembranes. Consequently, biomembranes are a prime target for resveratrol. However, its interactions with membrane lipids and precise localization within the cell membrane remain unclear and subject to debate. In this study, we investigated the electrokinetic behaviour of phosphatidylcholine (PC) liposomes and LN-18 human glioblastoma cells under the influence of resveratrol. Using the electrophoretic light scattering method, we monitored changes in electrokinetic (zeta) potential and membrane surface charge of both the <em>in vitro</em> models as a function of pH. Furthermore, we employed the MTT assay to assess the viability of RSV-treated cells. The measurements revealed the dose-dependent effects of RSV on the analyzed parameters of both liposomes and cells. Theoretical parameters, including surface concentrations of membrane groups and association constants, were derived through quantitative analysis of adsorption equilibria to characterize the binding of solution ions to glioblastoma cell membranes. Integrating theoretical insights with experimental findings is essential for a more comprehensive interpretation of the results.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111933"},"PeriodicalIF":5.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alisol B 23-acetate as a promising natural bioactive tetracyclic triterpenoid: A review of its extraction methods, pharmacokinetics, metabolism, pharmacology, and toxicity","authors":"Yinqi Wu ,&nbsp;Yu Du ,&nbsp;Zhichen Wang ,&nbsp;Yi Wu ,&nbsp;Zhen Li ,&nbsp;Aimin Wang ,&nbsp;Yuran Sun","doi":"10.1016/j.cbi.2026.111928","DOIUrl":"10.1016/j.cbi.2026.111928","url":null,"abstract":"<div><div>Natural compounds are increasingly gaining attention in modern pharmaceutical research due to their multiple therapeutic effects and low toxicity. Alisol B 23-acetate (AB23A), a naturally derived triterpenoid compound isolated from <em>Alisma orientale</em>(AO), exhibits a variety of pharmacological activities. It demonstrates significant therapeutic potential in the treatment of chronic atherosclerosis, anti-inflammatory responses, liver and kidney protection, as well as anticancer effects. Moreover, its low toxicity and high safety profile make it an attractive compound for researchers. This suggests that AB23A is a promising natural compound with substantial development potential. In this review, we systematically reviewed the extraction methods, pharmacokinetics, metabolism, pharmacology, and toxicity of AB23A. Additionally, the current research status of AB23A was comprehensively analyzed and summarized, providing valuable reference materials for further investigation and drug development.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111928"},"PeriodicalIF":5.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro recapitulation of drug metabolite partitioning into the bile and blood using the icHep system consisting of hepatocytes with an induced open-form bile canaliculus","authors":"Yuya Nakazono ,&nbsp;Naoki Ishiguro ,&nbsp;Mutsumi Inamatsu ,&nbsp;Atsuo Kobayashi ,&nbsp;Yoshiki Mochizuki ,&nbsp;Takashi Watanabe ,&nbsp;Yukihide Momozawa ,&nbsp;Chise Tateno ,&nbsp;Ikumi Tamai ,&nbsp;Hiroshi Arakawa","doi":"10.1016/j.cbi.2026.111931","DOIUrl":"10.1016/j.cbi.2026.111931","url":null,"abstract":"<div><div>For <em>in vitro</em> studies that predict the safety of systemically circulating drug metabolites, evaluating the formation and biliary excretion of hepatic drug metabolites in human hepatocytes is necessary. However, conventional sandwich-cultured hepatocytes (SCH) form closed bile canaliculi that preclude direct collection of excreted biliary metabolites. Therefore, this study assessed whether primary cultured hepatocytes with an induced open-form bile canaliculus (icHep) provide a suitable system for evaluating the partitioning of drug metabolites produced in hepatocytes into the bile-side and blood-side chambers. Hepatocytes derived from human liver chimeric mice were cultured on claudin-1-coated plates, which facilitated the formation of an open bile canalicular lumen, as confirmed by co-immunostaining for multidrug resistance-associated protein 2 and zonula occludens 1. RNA-sequencing analysis revealed that the expression of representative pharmacokinetic-related genes in the icHep system were comparable with those in conventional SCH. Following the addition of the parent drugs to the blood-side chamber of the permeation assay, metabolites were successfully collected from both the blood- and bile-side chambers. Ziprasidone sulfoxide and mycophenolic acid glucuronide were predominantly recovered from blood-side chamber, whereas celecoxib carboxylic acid and SN-38 glucuronide were preferentially excreted into the bile-side chamber. The partitioning of metabolites observed in the icHep system was consistent with human <em>in vivo</em> data. Overall, the icHep system enables evaluation of drug metabolite partitioning into the bile- and blood-side. Hence, this system represents a physiologically relevant <em>in vitro</em> system for human pharmacokinetic studies.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111931"},"PeriodicalIF":5.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl hydrocarbon receptor pathway mediates cigarette smoke-induced skin inflammation and sebaceous gland hyperplasia","authors":"Ying Xie ,&nbsp;Aoyin Liu ,&nbsp;Junqi Bai ,&nbsp;Baoling Xie ,&nbsp;Hankun Chen ,&nbsp;Yirui Liu ,&nbsp;Xian Zhang ,&nbsp;Wei Zhu","doi":"10.1016/j.cbi.2026.111930","DOIUrl":"10.1016/j.cbi.2026.111930","url":null,"abstract":"<div><div>Cigarette smoke (CS) represents a major exogenous stimulus associated with various skin pathologies, yet the precise mechanisms driving skin inflammation and glandular dysfunction remain incompletely elucidated. The aryl hydrocarbon receptor (AhR) is a transcription factor involved in various cellular functions, though its role in skin is unclear. This study investigates how cigarette smoke extract (CSE) mediates skin inflammation and abnormal glandular hyperplasia via AhR activation. In a CS-exposed mouse model, histopathological staining revealed that CS exposure induced inflammatory cell infiltration, mast cell degranulation and increased sebaceous gland cells. Immunohistochemistry showed higher levels of CD68, lymphocyte antigen 6 family member G (Ly-6G), and AhR, along with increased mRNA expression of inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). Integrated network toxicology and transcriptomics suggested that nicotine derivatives, indoles, and bipyridyl components in CSE activate the AhR complex, increasing cytochromes P450 family 1 (CYP1) subfamily A member 1 (CYP1A1), CYP1B1, and glutathione S-transferase (GST), while promoting the release of inflammatory mediators. Co-culture experiments with 3T3-L1 preadipocytes and RAW264.7 macrophages indicated that CSE-treated macrophages enhance adipocyte proliferation and lipid accumulation via paracrine signaling. In summary, CS exposure activates the AhR pathway, leading to increased inflammation and sebaceous gland cell proliferation, which collectively contribute to inflammatory infiltration, sebaceous gland hyperplasia, and collagen remodeling in skin tissue. These findings offer deeper theoretical insights for preventing and treating CS-related skin diseases.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111930"},"PeriodicalIF":5.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trojan horse tactics: Naphthalimide polyamine conjugates revolutionize cancer treatment","authors":"Zhiyong Tian ,&nbsp;Luyao Tian ,&nbsp;Chaojie Wang ,&nbsp;Suiqing Chen","doi":"10.1016/j.cbi.2026.111926","DOIUrl":"10.1016/j.cbi.2026.111926","url":null,"abstract":"<div><div>Naphthalimide polyamine conjugates (NPCs) represent a disruptive advance in anticancer drug development by employing multi-target strategies to overcome the limitations of traditional DNA intercalators. Unlike conventional naphthalimide drugs such as Amonafide, which show limited tumor inhibition (46.91 %) and significant toxicity, NPCs leverage the polyamine transporter (PAT) system for selective tumor accumulation—a ‘Trojan horse’ effect. This review highlights three key advances: (1) optimizing polyamine chain length and aromatic ring substitution (e.g., 3-nitro) to improve PAT affinity and DNA intercalation; (2) adopting multimodal mechanisms, including interference with polyamine metabolism via the SSAT/PAO pathway, leading to autophagy, EMT prevention, and DNA damage; and (3) developing PAT-mediated targeting and nanocarrier systems to enhance solid tumor penetration. Critically, the compelling <em>in vivo</em> efficacy of several lead NPCs, such as conjugate 5b, which achieved &gt;75 % inhibition of tumor growth and metastasis in HCC models, provides a solid foundation for this drug class. Innovations like dual-target conjugates (e.g., flavone-naphthalimide-polyamine) and computational modeling of drug-likeness and binding modes are emerging as promising tools for personalized oncology. Despite facing challenges in synthetic complexity and clinical translation, NPCs hold potential to address key clinical hurdles—poor pharmacokinetics, tumor penetration, and drug resistance—offering a breakthrough strategy for invasive and metastatic cancers.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111926"},"PeriodicalIF":5.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamic acid induces neurodevelopmental defects via PPARγ signaling in zebrafish","authors":"Lixia Peng ,&nbsp;Haoxu Wang ,&nbsp;Yafang Li ,&nbsp;Xiaoyu Liu ,&nbsp;Kaihui Chang ,&nbsp;Wenxin Yi ,&nbsp;Baokun Wang ,&nbsp;Nan Zeng ,&nbsp;Zhiqiang Li ,&nbsp;Chuanhong Wu","doi":"10.1016/j.cbi.2026.111929","DOIUrl":"10.1016/j.cbi.2026.111929","url":null,"abstract":"<div><div><em>Cinnamomum cassia</em> Presl is traditional used to warm the body, dispel cold and relieve pain in China. It is a commonly used traditional Chinese medicine and spice in daily heath care. Cinnamic acid (CA) is one of the main active compounds isolated from cinnamon bark. In the present study, we found that CA (4 mg/L and 8 mg/L) caused neurodevelopment defects in zebrafish as evidenced by shortened body length, trunk curvature, behavioral abnormalities and increased mortality. And we explored the potential targets and biological mechanisms of neurotoxicity caused by cinnamic acid using network toxicology and zebrafish experiments. 154 CA related target genes were shared with neurotoxicity-related genes. Using different algorithms in Cytoscape software, 4 key target genes were finally identified as TNF, CASP3, IL6 and PPARG, which were further confirmed with molecular docking. For the next, we confirmed these targets in zebrafish. CA up-regulated <em>tnf-α</em>, <em>il-6</em> and <em>casp</em><em>ase</em><em>3</em> gene expressions, and down-regulated <em>pparg</em> gene expression. Moreover, it can inhibit the activity of AChE, ATPases, CAT and SOD, decreased neuronal fluorescence, and increased macrophages and neutrophile granulocytes, ROS and MDA. In addition, it could induce apoptosis and abnormal neurodevelopmental-related gene expression in zebrafish larvae. Oxidative stress inhibitor astaxanthin could ameliorate the behavioral impairment and the expression of neurodevelopment-related genes. Moreover, when PPAR-γ expression was increased, the behavioral impairment, inflammatory response, oxidative stress, and apoptosis levels were alleviated. All these data demonstrated that the developmental neurotoxicity of CA in zebrafish might be attributed to PPAR-γ mediated oxidative stress, inflammatory response and apoptosis.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111929"},"PeriodicalIF":5.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The in vitro assessment of the prooxidative action of the novel aroylacrylic acid phenylamides in A549 and MCF7 cancer cell lines","authors":"Snežana K. Bjelogrlić ,&nbsp;Tamara Vujatović-Velimirov ,&nbsp;Aleksandra Korać ,&nbsp;Sara Stojanović ,&nbsp;Jelena Grahovac ,&nbsp;Maja D. Vitorović-Todorović","doi":"10.1016/j.cbi.2026.111925","DOIUrl":"10.1016/j.cbi.2026.111925","url":null,"abstract":"<div><div>Aroylacrylic acids, their phenylamides and other analogues bearing structural scaffold comprising of the two phenyl rings linked by three or four carbon atoms exert prominent anticancer activity. To unravel the relying mechanism responsible for induction of cell death by aroylacrylic acid phenylamides, we designed four novel structural analogues (<strong>1a</strong>-<strong>1d</strong>) by means of Michaels’ addition of secondary cyclic amines to aroylacrylic acid phenylamides. A battery of biological assays has been utilized to evaluate functional and morphological alterations triggered by the investigated treatments in A549 and MCF7 cell lines that are KRAS^mut and KRAS^wt, respectively, using carbonyl cyanide-<em>p</em>-trifluoromethoxyphenylhydrazone as a positive control. Concomitant treatment with, <em>N</em>-acetylcysteine reversed cell death response induced by investigated compounds (75.7 ± 15.1 % and 33.1 ± 9.9 % in average for MCF7 and A549 cells, respectively), suggesting that the generation of reactive oxidative species (ROS) was the key trigger of the cell death. Moreover, MCF7 cells were more susceptible to experimental treatments than A549 cells, whereas examination of the mitochondrial membrane potential and superoxide generation showed that the integrity of mitochondria in MCF7 cell line was devastated quickly after exposure to the investigated compounds. As KRAS^mut A549 cells have dysfunctional oxidative phosphorylation (OXPHOS), these results imply that the fully operative OXPHOS in KRAS^wt cells exceedingly amplified ROS production upon treatment. Additionally, ultrastructural analysis confirmed significant mitochondrial damage in both cell lines. Investigated compounds potently disrupt mitochondrial function and can serve as a valuable asset for testing capacity of new antioxidant agents.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111925"},"PeriodicalIF":5.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycyclic aromatic hydrocarbons-induced suppression of the PPARα/ACAA1 axis drives hepatic steatosis: Integrating epidemiology, network toxicology, and experimental validation","authors":"Haonan Cui ,&nbsp;Peng Zou ,&nbsp;Wang Yang ,&nbsp;Shijun He ,&nbsp;Jinyuan Shi ,&nbsp;Ting Sun ,&nbsp;Mengge Wang ,&nbsp;Zhiyong Song ,&nbsp;Hanni Guan ,&nbsp;Tong Wang ,&nbsp;Lei Sun ,&nbsp;Qing Chen ,&nbsp;Jinyi Liu ,&nbsp;Xi Ling ,&nbsp;Jia Cao ,&nbsp;Lin Ao","doi":"10.1016/j.cbi.2026.111923","DOIUrl":"10.1016/j.cbi.2026.111923","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) is a common liver condition linked to chronic hepatic dysfunction and systemic metabolic disorders. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent environmental pollutants associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, underlying molecular mechanisms linking PAH exposure to hepatic steatosis remain incompletely elucidated.</div></div><div><h3>Objectives</h3><div>This study aimed to clarify the association between PAHs exposure and NAFLD and unravel the core molecular pathways driving PAHs-induced hepatic lipid metabolism dysfunction.</div></div><div><h3>Methods</h3><div>Cross-sectional analyses were performed using data from the 2007–2016 National Health and Nutrition Examination Survey (NHANES) to investigate the associations of urinary PAH metabolites with NAFLD prevalence, hepatic steatosis index (HSI), and serum metabolic indicators. The relationships between PAHs and metabolic indicators were further validated in participants from the Preconception Reproductive Health and Birth Outcome Cohort (PREBIC). We then integrated network toxicology, bioinformatics, and both in vivo and in vitro models to elucidate the molecular pathways through which benzo[a]pyrene (BaP), a prototype PAHs, drives hepatic steatosis.</div></div><div><h3>Results</h3><div>Analyses of NHANES data revealed significant positive associations between PAHs exposure and NAFLD incidence, the hepatic steatosis index (HSI), and serum triglyceride (TG) level. Validation in the PREBIC cohort consistently confirmed the robust association between PAHs exposure and increased TG level. Elevated serum TG levels emerged as a key metabolic indictor of PAHs-induced hepatic steatosis. Network toxicology revealed that PPARα is a key molecular involved in lipid metabolism disruption by BaP, contributing to NAFLD. Integrated bioinformatics analyses further revealed that the binding of BaP to PPARα represses the expression of the downstream gene ACAA1. In vivo and in vitro experiments confirmed that BaP inhibits PPARα signaling, impairing peroxisomal function and fatty acid degradation and thus, leadings to hepatic lipid accumulation.</div></div><div><h3>Conclusion</h3><div>PAHs exposure is associated with hepatic steatosis and elevated serum TG level, and PPARα/ACAA1 axis suppression constitutes a key pathway through which BaP disrupts hepatic lipid metabolism. This study provides novel insights into the environmental etiology of NAFLD and identifies the PPARα/ACAA1 axis as a potential therapeutic target for PAHs-related NAFLD.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111923"},"PeriodicalIF":5.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyflumetofen disrupts the blood-brain barrier and induces neurotoxicity in zebrafish larvae","authors":"Wei-Guo Wang ,&nbsp;Yi-Min Duan ,&nbsp;Wen-Ping Xu,&nbsp;Li-Ming Tao,&nbsp;Yang Zhang,&nbsp;Jia-Gao Cheng","doi":"10.1016/j.cbi.2026.111911","DOIUrl":"10.1016/j.cbi.2026.111911","url":null,"abstract":"<div><div>Cyflumetofen is a novel non-systemic acylacetonitrile miticide widely used in agriculture to control various harmful mites. However, its potential safety risks to the nervous system of non-target organisms require further evaluation. Cyflumetofen induces developmental toxicity in zebrafish larvae, manifested as pericardial edema, yolk sac enlargement, and reduced body length. To evaluate the impact on the nervous system, cyflumetofen was found to damage neuronal and motor neuron cells in zebrafish larvae, reduce locomotor activity, and alter brain tissue structure. Additionally, cyflumetofen induces apoptosis in zebrafish larvae and leads to oxidative stress, which may be a critical pathway contributing to neurotoxicity. Furthermore, cyflumetofen disrupts the blood-brain barrier (BBB) structure in zebrafish larvae and reduces the levels of tight junction (TJ) proteins. Molecular-level studies reveal that cyflumetofen interferes with the Wnt/β-catenin signaling pathway and upregulates the expression levels of genes associated with Parkinson's disease (PD) pathogenesis (<em>pink1</em>, <em>parkin</em>, and <em>lrrk2</em>).</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111911"},"PeriodicalIF":5.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic kidney toxicity of polylactic acid nanoplastics and Cr(VI): Ferroptosis aggravated by mitophagy","authors":"Yuankun Zhou ,&nbsp;Jiajun Guo ,&nbsp;Xiaoyan Feng ,&nbsp;Hengyi Xu","doi":"10.1016/j.cbi.2026.111915","DOIUrl":"10.1016/j.cbi.2026.111915","url":null,"abstract":"<div><div>Nanoplastics (NPs) and chromium (Cr) are ubiquitous in the environment, causing severe pollution and posing significant potential threats to human health. Polylactic acid (PLA) and Cr are among widely used bioplastic and heavy metal, respectively, both capable of contaminating water sources through corresponding pathways and posing substantial risks to human health. Nanoplastics can act as carriers for heavy metals, thereby enhancing their bioaccumulation and toxicity. Therefore, this study investigated the effects of combined exposure to Cr(VI) and PLA NPs on mice kidneys and its potential mechanisms. Results indicated that exposure to PLA NPs alone did not exhibit significant toxic effects on the kidneys. However, combined exposure to Cr(VI) and PLA NPs caused severe kidney damage in mice. This indirectly suggests that Cr(VI) and PLA NPs exhibit synergistic toxicity rather than simple additive effects. Furthermore, combined exposure exacerbated the toxic mechanism by inducing mitochondrial damage and excessive reactive oxygen species (ROS) production, thereby triggering mitophagy. Overactivated mitophagy exacerbated lipid peroxidation by releasing free iron, thereby amplifying ROS-mediated ferroptosis. This study investigates the synergistic renal toxicity of Cr(VI) and PLA NPs, providing scientific evidence for the combined toxicity mechanism of exposure to MNPs and heavy metals.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111915"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}