Journal of Toxicological Sciences最新文献_第4页

Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method. 开发基于 GNN 的人工智能模型，用袋装法预测线粒体毒性。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.117

Yoshinobu Igarashi, Ryosuke Kojima, Shigeyuki Matsumoto, Hiroaki Iwata, Yasushi Okuno, Hiroshi Yamada

{"title":"Developing a GNN-based AI model to predict mitochondrial toxicity using the bagging method.","authors":"Yoshinobu Igarashi, Ryosuke Kojima, Shigeyuki Matsumoto, Hiroaki Iwata, Yasushi Okuno, Hiroshi Yamada","doi":"10.2131/jts.49.117","DOIUrl":"10.2131/jts.49.117","url":null,"abstract":"Mitochondrial toxicity has been implicated in the development of various toxicities, including hepatotoxicity. Therefore, mitochondrial toxicity has become a major screening factor in the early discovery phase of drug development. Several models have been developed to predict mitochondrial toxicity based on chemical structures. However, they only provide a binary classification of positive or negative results and do not provide the substructures that contribute to a positive decision. Therefore, we developed an artificial intelligence (AI) model to predict mitochondrial toxicity and visualize structural alerts. To construct the model, we used the open-source software library kMoL, which employs a graph neural network approach that allows learning from chemical structure data. We also utilized the integrated gradient method, which enables the visualization of substructures that contribute to positive results. The dataset used to construct the AI model exhibited a significant imbalance, with significantly more negative than positive data. To address this, we employed the bagging method, which resulted in a model with high predictive performance, as evidenced by an F1 score of 0.839. This model can also be used to visualize substructures that contribute to mitochondrial toxicity using the integrated gradient method. Our AI model predicts mitochondrial toxicity based on chemical structures and may contribute to screening mitochondrial toxicity in the early stages of drug discovery.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 3","pages":"117-126"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells. 木犀草素诱导鼻咽癌细胞铁变态反应的机制

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.399

Zhiyi Wu, Qingsong Qu

{"title":"Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells.","authors":"Zhiyi Wu, Qingsong Qu","doi":"10.2131/jts.49.399","DOIUrl":"https://doi.org/10.2131/jts.49.399","url":null,"abstract":"Nasopharyngeal carcinoma (NPC) originates from the nasopharynx epithelium, and luteolin is recognized as an important anti-cancer agent. This study investigated the effects of luteolin on ferroptosis in NPC cells. NPC cells were cultured and exposed to varying concentrations of luteolin. Cell viability, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione (GSH) levels, Fe2+ concentration, and glutathione peroxidase 4 (GPX4) protein level were assessed. Additionally, SRY-related high-mobility-group box 4 (SOX4) expression was measured. Subsequently, the binding of SOX4 to the growth differentiation factor-15 (GDF15) promoter and GDF15 mRNA levels were evaluated. The impact of the SOX4/GDF15 axis on luteolin-induced ferroptosis in NPC cells was assayed. Luteolin treatment induced cell ferroptosis, evidenced by decreased cell viability, increased MDA and Fe2+ levels, and reduced SOD, GSH, and GPX4 levels. Furthermore, luteolin downregulated SOX4 expression, while overexpression of SOX4 reversed luteolin's pro-ferroptotic effects in NPC cells. SOX4 was found to up-regulate GDF15 transcription by directly binding to its promoter. Conversely, overexpression of GDF15 mitigated the ferroptotic effects induced by luteolin in NPC cells. Therefore, luteolin induces ferroptosis in NPC cells via modulation of the SOX4/GDF15 axis. In conclusion, luteolin reduces the binding of SOX4 to the GDF15 promoter by suppressing SOX4 expression, thereby down-regulating GDF15 transcription levels and inducing ferroptosis in NPC cells.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 9","pages":"399-408"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A case of infant death due to chlorfenapyr poisoning. 氯虫那韦中毒致婴儿死亡1例。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.549

Limei Mo, Hongyan Wu, Li Zhao, Kang An

{"title":"A case of infant death due to chlorfenapyr poisoning.","authors":"Limei Mo, Hongyan Wu, Li Zhao, Kang An","doi":"10.2131/jts.49.549","DOIUrl":"10.2131/jts.49.549","url":null,"abstract":"Chlorfenapyr is a novel pyrrole compound with the chemical formula C15H11BrClF3N2O, exhibiting potent insecticidal and acaricidal effects. It primarily acts on the multi-functional oxidases in the mitochondria of insects, inhibiting the conversion of adenosine diphosphate to adenosine triphosphate, leading to cellular dysfunction due to energy depletion. With increased production and market availability, the population's exposure to chlorfenapyr has risen, resulting in a growing number of fatal poisoning incidents. This report describes the clinical presentation, disease progression, and treatment outcomes of a 2-year and 11-month-old toddler poisoned with chlorfenapyr. The child exhibited symptoms of nausea and vomiting two hours post-poisoning, received gastric lavage and fluid replacement at the local hospital, and was subsequently transferred to our facility. On admission, the child's vital signs were stable for the first two days, with normal laboratory findings. On the third day, the child showed signs of fatigue and diaphoresis, followed by high fever, profuse sweating, altered consciousness, and muscle tremors on the fourth day. By the fifth day, the child displayed rigid muscles in the limbs and trunk, respiratory and circulatory failure, despite rescue efforts proving futile, leading to eventual demise.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 12","pages":"549-553"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Industrially produced trans-fatty acids are potent promoters of DNA damage-induced apoptosis. 工业生产的反式脂肪酸是 DNA 损伤诱导细胞凋亡的强力促进剂。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.27

Yusuke Hirata, Ryota Kojima, Ryo Ashida, Yuki Nada, Shinnosuke Kimura, Emiko Sato, Takuya Noguchi, Atsushi Matsuzawa

{"title":"Industrially produced trans-fatty acids are potent promoters of DNA damage-induced apoptosis.","authors":"Yusuke Hirata, Ryota Kojima, Ryo Ashida, Yuki Nada, Shinnosuke Kimura, Emiko Sato, Takuya Noguchi, Atsushi Matsuzawa","doi":"10.2131/jts.49.27","DOIUrl":"https://doi.org/10.2131/jts.49.27","url":null,"abstract":"trans-Fatty acids (TFAs) are unsaturated fatty acids harboring at least one carbon-carbon double bond in trans configuration, which are categorized into two groups according to their origin: industrial and ruminant TFAs, hereafter called iTFAs and rTFAs, respectively. Numerous epidemiological studies have shown a specific link of iTFAs to various diseases, such as cardiovascular and neurodegenerative diseases. However, there is little evidence for underlying mechanisms that can explain the specific toxicity of iTFAs, and how to mitigate their toxicity. Herein, we show that iTFAs, including elaidic acid (EA) and linoelaidic acid, but not rTFAs, facilitate apoptosis induced by doxorubicin (Dox), triggering DNA double-strand breaks. We previously established that EA promotes Dox-induced apoptosis by accelerating c-Jun N-terminal kinase (JNK) activation through mitochondrial reactive oxygen species (ROS) overproduction. Consistently, iTFAs specifically enhanced Dox-induced JNK activation. Furthermore, Dox-induced pro-apoptotic signaling by iTFAs was blocked in the presence of oleic acid (OA), the geometrical cis isomer of EA. These results demonstrate that iTFAs specifically exert their toxicity during DNA damage-induced apoptosis, which could be effectively suppressed by OA. Our study provides evidence for understanding the difference in toxic actions between TFA species, and for new strategies to prevent and combat TFA-related diseases.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 1","pages":"27-36"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Involvement of microRNA-4680-3p against phenytoin-induced cell proliferation inhibition in human palate cells. microRNA-4680-3p参与了苯妥英诱导的人腭细胞增殖抑制作用。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.1

Yosuke Tsukiboshi, Hanane Horita, Yurie Mikami, Azumi Noguchi, Satoshi Yokota, Kenichi Ogata, Hiroki Yoshioka

引用次数: 0

Identification of post-mortem product of zolpidem degradation by hemoglobin via the Fenton reaction. 通过芬顿反应鉴定血红蛋白降解唑吡坦的尸检产物。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.261

Yoshikazu Yamagishi, Sayaka Nagasawa, Hirotaro Iwase, Yasumitsu Ogra

{"title":"Identification of post-mortem product of zolpidem degradation by hemoglobin via the Fenton reaction.","authors":"Yoshikazu Yamagishi, Sayaka Nagasawa, Hirotaro Iwase, Yasumitsu Ogra","doi":"10.2131/jts.49.261","DOIUrl":"10.2131/jts.49.261","url":null,"abstract":"Zolpidem, N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide, is a hypnotic agent widely used in clinical practice but is detected in many clinical cases of fatal intoxication and suicide. In forensic toxicology, the precise determination of zolpidem concentration in blood is a must to provide concrete evidence of death by zolpidem poisoning. However, the concentrations of zolpidem in blood at autopsy often differ from those at the estimated time of death. In the present study, we found that zolpidem was degraded by hemoglobin (Hb) via the Fenton reaction at various temperatures. The mechanism underlying zolpidem degradation involved the oxidation of its linker moiety. The MS and MS/MS spectra obtained by liquid chromatography quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap-MS) showed the formation of 2-hydroxy-N,N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetamide (2-OH ZOL) in Hb/H2O2 solution incubated with zolpidem and in the blood of several individuals who died from ingestion of zolpidem. These results suggest that 2-OH ZOL is the post-mortem product of zolpidem degradation by Hb via the Fenton reaction.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 6","pages":"261-268"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation of a new protocol for a zebrafish MEFL (malformation or embryo-fetal lethality) test method that conforms to the ICH S5 (R3) guideline. 验证符合 ICH S5 (R3) 指南的斑马鱼畸形或胚胎-胎儿致死率（MEFL）检测方法新方案。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.337

Kanako Mori, Yoshinobu Aoki, Fumito Mikashima, Kazushige Maki, Toshio Tanaka, Mai Hayashi, Wataru Sugimoto, Mizuho Ono, Saaya Umekita, Tatsuhiro Niino, Michio Fujiwara, Tomonori Ebata, Hiromi Hirata, Hajime Kojima

{"title":"Validation of a new protocol for a zebrafish MEFL (malformation or embryo-fetal lethality) test method that conforms to the ICH S5 (R3) guideline.","authors":"Kanako Mori, Yoshinobu Aoki, Fumito Mikashima, Kazushige Maki, Toshio Tanaka, Mai Hayashi, Wataru Sugimoto, Mizuho Ono, Saaya Umekita, Tatsuhiro Niino, Michio Fujiwara, Tomonori Ebata, Hiromi Hirata, Hajime Kojima","doi":"10.2131/jts.49.337","DOIUrl":"https://doi.org/10.2131/jts.49.337","url":null,"abstract":"Detecting the toxic effects of chemicals on reproduction and development without using mammalian animal models is crucial in the exploitation of pharmaceuticals for human use. Zebrafish are a promising animal model for investigating pharmacological effects and toxicity during vertebrate development. Several studies have suggested the use of zebrafish embryos for the assessment of malformations or embryo-fetal lethality (MEFL). However, a reproducible protocol as a standard for the zebrafish MEFL test method that fulfills global requests has not been established based on the International Council of Harmonisation (ICH) S5 (R3) guidelines. To establish such a toxicity test method, we developed a new and easy protocol to detect MEFL caused by chemicals, especially those with teratogenic potential, using fertilized zebrafish eggs (embryos) within 5 days of development. Our toxicity test trials using the same protocol in two to four different laboratories corroborated the high inter-laboratory reproducibility. Our test method enabled the detection of 18 out of 22 test compounds that induced rat MEFL. Thus, the prediction rate of our zebrafish test method for MEFL was almost 82% compared with that of rat MEFL. Collectively, our study proposes the establishment of an easy and reproducible protocol for the zebrafish MEFL test method for reproductive and developmental toxicity that meets ICH guideline S5 (R3), which can be further considered in combination with information from other sources for regulatory use.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 8","pages":"337-348"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Resin monomers induce apoptosis of the pulp-dentin complex through the mitochondrial pathway. 树脂单体通过线粒体途径诱导牙本质复合物的凋亡。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.531

Siqi Xu, Lijuan Chen, Xi Lin, Xiaoxia Yang, Lidan He, Siqi Yan, Song Luo, Xinyi Chen, Guoying Que

{"title":"Resin monomers induce apoptosis of the pulp-dentin complex through the mitochondrial pathway.","authors":"Siqi Xu, Lijuan Chen, Xi Lin, Xiaoxia Yang, Lidan He, Siqi Yan, Song Luo, Xinyi Chen, Guoying Que","doi":"10.2131/jts.49.531","DOIUrl":"https://doi.org/10.2131/jts.49.531","url":null,"abstract":"Numerous studies have confirmed that the apoptosis induced by the methacrylate resin monomers triethyleneglycol-dimethacrylate (TEGDMA), 2-hydroxy ethyl methacrylate (HEMA), etc., in pulp cells and odontoblast-like cells is caused mainly by oxidative stress (OS). Reactive oxygen species (ROS), recognized as the most important risk factor for apoptosis in cells of the pulp-dentin complex, are produced mainly via the mitochondrial respiratory chain. When the free resin monomers in the oral cavity and pulp reach a toxic level, the monomers induce oxidative DNA damage, activate ATM-p53 in the nucleus, and mediate the intrinsic apoptotic pathway in the presence of Bcl-2 family proteins. A vicious cycle is established between OS cellular responses and abnormalities in mitochondrial dynamics that accelerate apoptosis. Despite numerous products generated via iteration, complete polymerization of resin monomers is not currently possible. The cytotoxicity of free monomers may lead to adverse reactions, such as pulp sensitivity. This review is based on the most important papers describing the roles of resin monomers in mediating apoptosis in the pulp-dentin complex and provides an overview of the precise mechanisms related to mitochondrion-mediated cytotoxicity, suggesting ways to reduce or eliminate their cytotoxicity in the future through advancements in material technology.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 12","pages":"531-541"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nafamostat mesylate sensitizes ovarian cancer cells to carboplatin by promoting the ZNF24-mediated inhibition of WNT2B. 甲磺酸萘莫司他通过促进 ZNF24 介导的 WNT2B 抑制作用，使卵巢癌细胞对卡铂敏感。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.467

Jiehuan Xu, Jianlin Chen, Dao Wang, Yaojun Li, Ping Lian, Xiaozhu Wu, Rong Yan

{"title":"Nafamostat mesylate sensitizes ovarian cancer cells to carboplatin by promoting the ZNF24-mediated inhibition of WNT2B.","authors":"Jiehuan Xu, Jianlin Chen, Dao Wang, Yaojun Li, Ping Lian, Xiaozhu Wu, Rong Yan","doi":"10.2131/jts.49.467","DOIUrl":"https://doi.org/10.2131/jts.49.467","url":null,"abstract":"Resistance to chemotherapeutic medicines complicates and eventually kills people with ovarian cancer. Nafamostat mesylate (NM) has been used as an adjuvant therapy to enhance chemotherapy sensitivity in several cancers. This study aimed to evaluate the effect of NM on ovarian cancer cells susceptible to carboplatin (CBP) and to determine the underlying mechanism involved. Herein, qRT-PCR, western blot, and IHC were used to analyze mRNA and protein expression. Cell viability and proliferation were measured using the MTT and colony formation assays. Cell migration and invasion were examined using the Transwell assay. Flow cytometry was employed to detect cell apoptosis. The interaction between zinc finger protein 24 (ZNF24) and wingless-type MMTV integration site family member 2b (WNT2B) was validated via the dual-luciferase reporter and Chromatin immunoprecipitation assays. A xenograft nude mouse model was used to assess the effect of NM on CBP sensitivity in vivo. Our results showed that NM intervention inhibited the viability, proliferation, migration, and invasion and facilitated the apoptosis of CBP-resistant ovarian cancer cells. Furthermore, NM sensitized ovarian cancer cells to CBP by upregulating ZNF24. ZNF24 inactivated Wnt/β-catenin signaling by inhibiting the transcription of WNT2B. Additionally, NM enhanced the inhibitory effect of CBP on tumor growth in vivo. Taken together, NM enhanced the CBP sensitivity of ovarian cancer cells by promoting the ZNF24-mediated inactivation of the WNT2B/Wnt/β-catenin axis. These findings suggest a viable treatment approach for improving CBP resistance in ovarian cancer.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 11","pages":"467-479"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A single dose of clothianidin exposure induces varying sex-specific behavioral changes in adulthood depending on the developmental stage of its administration. 单剂量氯虫苯甲酰胺会在成年期诱发不同性别的行为变化，具体取决于给药的发育阶段。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.301

Kenshi Kaku, Takahiro Sasaki, Kenshiro Hara, Kentaro Tanemura

{"title":"A single dose of clothianidin exposure induces varying sex-specific behavioral changes in adulthood depending on the developmental stage of its administration.","authors":"Kenshi Kaku, Takahiro Sasaki, Kenshiro Hara, Kentaro Tanemura","doi":"10.2131/jts.49.301","DOIUrl":"https://doi.org/10.2131/jts.49.301","url":null,"abstract":"Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 7","pages":"301-311"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0