Toxicology and applied pharmacology最新文献

{"title":"Cadmium-induced apoptosis of granulosa cells is mediated by excessive activation of mitophagy and ROS-mediated mitochondrial dysfunction","authors":"Wenqian Li ,&nbsp;Mengqi Wu ,&nbsp;Haotian Shi ,&nbsp;Muran He ,&nbsp;Junyue Wang ,&nbsp;Yichao Huang ,&nbsp;Dexiang Xu ,&nbsp;Jun Zhang","doi":"10.1016/j.taap.2025.117462","DOIUrl":"10.1016/j.taap.2025.117462","url":null,"abstract":"<div><div>Cadmium (Cd), a pervasive environmental and occupational toxicant, has raised significant public health concerns due to its detrimental effects on human health. Emerging evidence highlights its capacity to impair the female reproductive system, notably through induction of follicular cell apoptosis. However, the underlying mechanism of Cd-induced apoptosis of granulosa cells remains unclear. In this study, thirty female mice were randomly allocated into three groups and exposed to CdCl₂ (0, 1.0, or 4.0 mg/kg) for 12 h, while 40 mice were divided into four groups and treated with CdCl₂ (4 mg/kg) for varying durations (0, 6, 12, or 24 h). Ovarian injury, apoptosis and mitophagy were observed in mice. To further elucidate the mechanism, human ovarian granulosa-like tumor cells (KGN cells) were treated with CdCl₂ (0–40 μM). Cd triggered apoptosis and excessive mitophagy in KGN cells, accompanied by reduced adenosine triphosphate (ATP) levels, diminished mitochondrial membrane potential (MMP), and elevated total reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Pharmacological inhibition of autophagy using 3-methyladenine (3-MA) attenuated Cd-induced apoptosis and mitochondrial dysfunction, whereas autophagy activation via rapamycin exacerbated these detrimental effects. Our findings demonstrate that Cd disrupts mitochondrial homeostasis by over activating mitophagy, which subsequently amplifies apoptotic signaling in ovarian granulosa cells. These results provide mechanistic insights into Cd-associated ovarian pathologies and highlight the therapeutic potential of targeting mitophagy to mitigate reproductive toxicity.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"503 ","pages":"Article 117462"},"PeriodicalIF":3.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627152","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":"Preclinical pharmacokinetic and toxicokinetic profiles of AY-1001 (IsoLiPro), a novel small molecule lithium-organic coordination compound","authors":"Yi Guo ,&nbsp;Bingjie Zhang ,&nbsp;Chuanbin Cai ,&nbsp;Qinmin Tang ,&nbsp;Zhifeng Lei ,&nbsp;Jiang Chen ,&nbsp;Xiaojiang Zheng ,&nbsp;Shaowei Lei ,&nbsp;Weidi Zhang ,&nbsp;Dan Zi ,&nbsp;Jun Tan ,&nbsp;Song Li","doi":"10.1016/j.taap.2025.117459","DOIUrl":"10.1016/j.taap.2025.117459","url":null,"abstract":"<div><div>Lithium is recommended as a first-line option for maintenance therapy of bipolar disorder (BD), due to its reliable mood-stabilizing property and benefits for relapse and suicide prevention. However, its clinical applications are still facing challenges, considering the relatively narrow therapeutic window, poor ability to cross the blood-brain barrier, and various side-effects ranging from mild nonspecific to life threatening symptoms. To overcome these challenges, the discovery and development of novel lithium-containing candidates with better kinetics profiles is urgently needed. We previously synthesized and patented a novel lithium-containing coordination compound AY-1001 (C₉H₁₆LiNO₄), which shows antimanic activity in animal model. In this study, the pharmacokinetic and toxicokinetic properties of AY-1001 were further determined. Pharmacokinetic data demonstrated that AY-1001 has a faster onset of action, a shorter half-life, and a higher blood-brain barrier transmission rate, compared with the traditional inorganic lithium carbonate. In addition, toxicological data indicated that AY-1001 exhibits low toxicity in SD rats and beagle dogs. These findings suggest that AY-1001 has the potential to improve therapeutic effects and reduce side effects, providing a strong scientific basis and promising strategy for the further development of organic lithium-containing mood stabilizers.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"503 ","pages":"Article 117459"},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609629","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":"Gallium maltolate and cisplatin co-treatment effectively targets triple-negative breast cancer in spheroid and mouse models","authors":"Ya-Wen Yang ,&nbsp;Yu-Chen Hsieh ,&nbsp;Ching-Yu Liu ,&nbsp;Chun-Kai Pan ,&nbsp;Zi-Yu Pan ,&nbsp;Kai-Yin Lo","doi":"10.1016/j.taap.2025.117460","DOIUrl":"10.1016/j.taap.2025.117460","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks targeted therapies and is characterized by high invasiveness and metastatic potential. Our previous work demonstrated that GaM (gallium maltolate) blocks cell cycle progression and impairs ribosomal synthesis in TNBC cells. Moreover, GaM treatment promotes ferroptosis activation, and its combination with cisplatin exhibits synergistic effects. To further evaluate the efficacy of these treatments, we applied them to three-dimensional spheroid and mouse models. Two types of spheroids were generated: one composed solely of TNBC cells (MDA-MB-231) and the other a co-culture with normal breast cells (MCF10A). In both MDA/MCF10A and MDA-MB-231 spheroids, we observed enhanced p53 activation and increased p21 expression, with the effects being more pronounced in the MDA-MB-231 spheroids. These effects were stronger with the combination treatment than with either treatment alone. Similar results were observed in a xenograft model, where tumors formed from MDA-MB-231 cells in nude mice. The combination therapy reduced tumor size to a similar extent as cisplatin alone and did not cause adverse effects in mice. The combination therapy induced apoptosis, nucleolar stress, and ferroptosis. Additionally, the treatment inhibited cell migration and metastasis - by increasing E-cadherin levels and reducing metalloproteases. These findings provide a strong foundation for further mechanistic studies and potential clinical applications.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117460"},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596194","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":"Vitamin D alleviates silica-induced pulmonary fibrosis partly by inhibiting STAT3/hexokinase 2-mediated fibroblast glycolysis","authors":"Huanyu Yang ,&nbsp;Li Zhang ,&nbsp;Guanming Chen ,&nbsp;Qiongxiao Wu ,&nbsp;Mingyi Li ,&nbsp;Chengye Zhang ,&nbsp;Mengjia Han ,&nbsp;Qi Xu","doi":"10.1016/j.taap.2025.117456","DOIUrl":"10.1016/j.taap.2025.117456","url":null,"abstract":"<div><div>Pulmonary fibrosis is defined by the excessive accumulation of extracellular matrix proteins, with few treatment options currently available. Notably, emerging evidence indicates that vitamin D may provide benefits for fibrotic lesions across various tissues. However, the underlying molecular mechanisms have not yet been fully elucidated. In our study, we observed that glycolysis levels increased during the fibroblast-to-myofibroblast transition (FMT) in both MRC-5 cells and mouse primary lung fibroblasts, however, vitamin D treatment inhibited fibroblasts' activation, proliferation, and glycolysis <em>in vitro</em>. We further identified signal transducer and activator of transcription 3 (STAT3) as a crucial downstream effector of vitamin D, with the expression of phosphorylated STAT3 (p-STAT3) being negatively regulated by vitamin D. In MRC-5 cells and mouse primary lung fibroblasts, ectopic expression of STAT3 enhanced fibroblast activation and blocked the anti-fibrotic effects of vitamin D. Mechanistic studies revealed that vitamin D reduces p-STAT3 levels, which inhibits the expression of hexokinase-II (HK2), a key enzyme in the glycolytic pathway, consequently blocking fibroblast glycolysis and activation. <em>In vivo</em> experiments demonstrated that vitamin D administration significantly mitigated silica-induced fibrogenesis, while a deficiency in vitamin D exacerbated the progression of pulmonary fibrosis. Collectively, our findings suggest that vitamin D alleviates silica-induced pulmonary fibrosis by inhibiting fibroblast glycolysis in a STAT3/HK2-dependent manner, indicating that vitamin D supplementation may serve as a promising antifibrotic agent.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"503 ","pages":"Article 117456"},"PeriodicalIF":3.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596584","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":"Novel NLRP3 inhibitors mitigate acute radiation-induced lung injury by suppressing pyroptosis in alveolar epithelial cells","authors":"Yupeng Zhi ,&nbsp;Huijia Chen ,&nbsp;Yihao Huang ,&nbsp;Lipeng Li ,&nbsp;Zibin Chen ,&nbsp;Hongzhao Huang ,&nbsp;Fang Ke ,&nbsp;Yansong Guo ,&nbsp;Chun Chen","doi":"10.1016/j.taap.2025.117458","DOIUrl":"10.1016/j.taap.2025.117458","url":null,"abstract":"<div><h3>Objective</h3><div>Radiation-induced lung injury (RILI), a severe complication of thoracic tumor radiotherapy, is driven by NLRP3-mediated pyroptosis triggered by irradiation. This study aimed to design novel NLRP3 inhibitors targeting pyroptosis in alveolar epithelial cells to alleviate RILI and elucidate underlying mechanisms.</div></div><div><h3>Methods</h3><div>Quinoxalinone derivatives (QK-3A – QK-3E) targeting the NACHT domain of NLRP3 were synthesized. Their effects on the NLRP3/GSDMD pathway and cytokines (IL-1β, IL-18) were evaluated in irradiated A549 and MLE-12 cells using high-content Screening. A C57BL/6 mouse RILI model assessed compound efficacy via HE staining, Western blot, immunofluorescence. Safety was evaluated.</div></div><div><h3>Results</h3><div>Single-cell sequencing datasets analysis revealed a marked reduction in alveolar type 2 (AT2) cell proportion (from 12.41 % to 4.02 %) during early RILI, with pyroptosis-related genes showing heightened activity in AT2 cells. Molecular docking demonstrated QK-3E's strong binding to NLRP3 residues ARG351 and PHE575, inhibiting its activation. In vitro, QK-3D and QK-3E reduced radiation-induced cleaved-caspase-1/GSDMD-N expression(about 30 %–75 %), and IL-1β/IL-18 releases(about 30 %–50 %), suppressing AT2 pyroptosis. In vivo, QK-3D and QK-3E attenuated lung index elevation(about 25 %), mitigated pulmonary and systemic inflammation, and outperformed dexamethasone. They downregulated GSDMD-N(about 20 %-30) and cleaved-caspase-1(about 50 %–60 %) in SPC⁺ AT2 cells, blocking pyroptosis without cardiotoxicity, hepatotoxicity, or nephrotoxicity.</div></div><div><h3>Conclusion</h3><div>The NLRP3 inhibitors QK-3D and QK-3E effectively alleviate RILI by suppressing AT2 pyroptosis via NLRP3/GSDMD pathway inhibition, offering a potent and safe therapeutic candidate for early intervention. This study advances pyroptosis-targeted strategies for inflammatory diseases.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117458"},"PeriodicalIF":3.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572241","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":"Machine learning-driven prediction of eye irritation toxicity: Integration of in silico and in vitro study","authors":"Shanshan Chen ,&nbsp;Jiaxin Wang ,&nbsp;Lu Hao ,&nbsp;Ying Wan ,&nbsp;Yang Yu ,&nbsp;Yiwei Wang","doi":"10.1016/j.taap.2025.117457","DOIUrl":"10.1016/j.taap.2025.117457","url":null,"abstract":"<div><div>Eye irritation (EI) toxicity poses critical challenges in chemical safety assessment, demanding alternatives to ethically contentious animal testing. We present the first integrative framework combining computational prediction with experimental validation for EI evaluation. Utilizing 5220 compounds characterized by 11 molecular fingerprints and 13 molecular descriptors (MDs), six machine learning (ML) algorithms generated 252 models through rigorous five-fold cross-validation. The optimized model demonstrated exceptional predictive accuracy (0.977 test-set performance), surpassing comparable approaches. Experimental validation assessed model-predicted compounds through <em>in vitro</em> corneal epithelial assays, with benchmarked biological responses confirming prediction reliability. This closed-loop methodology establishes a paradigm for ethical chemical safety assessment, achieving three critical advancements: replacement of animal testing through computational-experimental synergy, enhanced prediction reliability <em>via</em> machine learning-optimized feature selection, and accelerated developmental timelines through early-stage toxicity screening. The validated approach addresses interspecies extrapolation limitations while aligning with global 3Rs (Replacement, Reduction, Refinement) initiatives, offering transformative potential for next-generation risk assessment in chemical development.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117457"},"PeriodicalIF":3.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563563","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":"NLRP3 inflammasome regulates doxorubicin-induced cardiotoxicity by modulating the abundance of gut microbiota","authors":"Jinsong Yin ,&nbsp;Yuyun You ,&nbsp;Juncong Mao ,&nbsp;Jialong Qi ,&nbsp;Xin Zhang ,&nbsp;Yunfei Hong","doi":"10.1016/j.taap.2025.117455","DOIUrl":"10.1016/j.taap.2025.117455","url":null,"abstract":"<div><div>Doxorubicin (DOX) is a widely used anthracycline whose dose-dependent cardiotoxicity limits its clinical efficacy. However, the mechanisms underlying its toxicity, particularly the regulatory network involving the Nod-like receptor protein 3 (NLRP3) inflammasome-gut-heart axis, remain incompletely understood. This study aimed to establish cellular and animal models of doxorubicin-induced cardiotoxicity (DIC) and investigate the role of the inflammasome in DIC-associated alterations in gut microbiota abundance. Rat cardiomyocytes (H9c2 cells) were treated with DOX 1, 10, 25, and 50 μmol/L concentrations to assess dose-dependent cardiotoxicity. In vivo, C57BL/6 J and NLRP3/MLKL/RIPK3 knockout (KO) mice received DOX (5 mg/kg, intravenous, every 2 days for 3 doses, cumulative 15 mg/kg) to establish a DIC model. We measured the physiological and biochemical parameters of mice peripheral blood using an automatic biochemical analyzer. Additionally, we quantified the mRNA expression levels of inflammatory factors using a reverse transcription polymerase chain reaction and observed cardiomyocyte apoptosis. Fecal samples were collected from each group for 16S recombinant DNA sequencing to analyze gut microbiota. DOX-induced H9c2 cell damage and inflammatory factor release activated the NLRP3 inflammasome and upregulated autophagy-associated proteins LC3I/II. NLRP3 KO attenuated DOX-induced cardiac damage, modulated the immune environment in mouse blood, and mitigated DIC. NLRP3 KO lowered the abundance of mucinophilic <em>Akkermansia muciniphila</em> and suppressed the cardiotoxic effects of DOX. The cardiotoxic effects of DOX were mediated via the NLRP3 inflammasome. NLRP3 inflammasome may mediate DIC by regulating the abundance of gut <em>Akkermansia muciniphila</em>.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117455"},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555030","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":"Deguelin inhibits IL-1β-induced chondrocyte inflammation in vitro and ameliorates murine osteoarthritis in vivo","authors":"Yanben Wang ,&nbsp;Jiaqing Ji ,&nbsp;Abudureyimu abudukeremu ,&nbsp;Dang Ma ,&nbsp;Ziyue Yin ,&nbsp;Kangshuai Xu ,&nbsp;Jian Fan","doi":"10.1016/j.taap.2025.117453","DOIUrl":"10.1016/j.taap.2025.117453","url":null,"abstract":"<div><div>Osteoarthritis (OA), a prevalent age-related degenerative joint disorder, is characterized by progressive articular cartilage degradation accompanied by subchondral bone remodeling, synovitis, and reactive osteophytosis. Discovering natural medicines capable of inhibiting inflammatory response of chondrocytes and cartilage degeneration is necessary for OA treatment. Emerging investigations have systematically demonstrated deguelin's multimodal anti-inflammatory efficacy mechanistically across multiple pathological contexts. However, its effect on chondrocytes remains unknown. Through a dual-level investigation combining in vitro mechanistic analysis and in vivo disease modeling, this study delineates deguelin's chondroprotective mechanisms in primary murine chondrocytes, while demonstrating potent disease-modifying effects in surgically induced OA pathogenesis. Deguelin demonstrated significant anti-inflammatory activity in IL-1β-activated chondrocytes. It diminished cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA and protein levels, and it prevented extracellular matrix (ECM) catabolism by reducing matrix metalloproteinases (MMPs) expression. Mechanistically, deguelin exerted anti-inflammatory effects through targeted suppression of NF-κB pathway activation, as confirmed by immunofluorescence and western blot analyses. Consistent with the in vitro findings, deguelin treatment protected against articular cartilage erosion and subchondral bone loss in OA murine model in vivo, suggesting its potential as an effective agent for treating OA.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117453"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529679","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":"Corrigendum to “Co-delivery of celastrol and lutein with pH sensitive nano micelles for treating acute kidney injury” [Toxicology and Applied Pharmacology Volume 450, 1 September 2022, 116155]","authors":"Mengxue Pang ,&nbsp;Songchao Duan ,&nbsp;Mengmeng Zhao ,&nbsp;Qingqing Jiao ,&nbsp;Yimeng Bai ,&nbsp;Lili Yu ,&nbsp;Bin Du ,&nbsp;Genyang Cheng","doi":"10.1016/j.taap.2025.117451","DOIUrl":"10.1016/j.taap.2025.117451","url":null,"abstract":"","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117451"},"PeriodicalIF":3.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508420","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":"Effect of parental perinatal exposure to L-glutamate monosodium salt monohydrate on developmental neurotoxicity in rat offspring","authors":"Zizhao Huang ,&nbsp;Xiao Xiao ,&nbsp;Xuan Zhang ,&nbsp;Haijiao Jiang ,&nbsp;Xiulan Zhao ,&nbsp;Qinzhi Wei ,&nbsp;Xingfen Yang ,&nbsp;Haixia Sui ,&nbsp;Tong Ou ,&nbsp;Daoyuan Yang ,&nbsp;Weichunbai Zhang ,&nbsp;Xudong Jia ,&nbsp;Yan Song ,&nbsp;Ling Yong","doi":"10.1016/j.taap.2025.117450","DOIUrl":"10.1016/j.taap.2025.117450","url":null,"abstract":"<div><div>This study aimed to provide preliminary information about the potential adverse effects of L-Glutamate Monosodium Salt Monohydrate on maternal health and offspring development, particularly about developmental neurotoxicity and abnormal behavior in offspring after oral administration by gavage to female SD rats during the perinatal stage. The study involved administering different doses of L-glutamate monosodium salt monohydrate to four groups, including a vehicle control group. The doses were given orally via gavage from gestation day 6 (GD6) until postnatal day 21 (PND21) at levels of 6000, 3000, and 1000 mg/kg BW. The study found that parental exposure to L-Glutamate Monosodium Salt Monohydrate at a dose of 6000 mg/kg BW had adverse effects on the growth and development of the offspring. These effects included delayed physical development and reflex development. However, no effects on dams were observed. The Lowest Observed Adverse Effect Level (LOAEL) for developmental toxicity to the offspring is 6000 mg/kg BW, and the No Observed Adverse Effect Level (NOAEL) is 3000 mg/kg BW. Additionally, the NOAEL for maternal toxicity is considered to be 6000 mg/kg BW.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117450"},"PeriodicalIF":3.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508421","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}