Journal of Toxicological Sciences最新文献_第9页

Glasgow coma scale may be a predictive factor for delayed neurological sequelae after carbon monoxide poisoning: a retrospective analysis of a nationwide multicenter observational registry in Japan. 格拉斯哥昏迷量表可能是一氧化碳中毒后迟发性神经系统后遗症的预测因素：一项对日本全国多中心观察登记的回顾性分析。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.69

Tadashi Kaneko, Motoki Fujita, Ryosuke Tsuruta

{"title":"Glasgow coma scale may be a predictive factor for delayed neurological sequelae after carbon monoxide poisoning: a retrospective analysis of a nationwide multicenter observational registry in Japan.","authors":"Tadashi Kaneko, Motoki Fujita, Ryosuke Tsuruta","doi":"10.2131/jts.50.69","DOIUrl":"10.2131/jts.50.69","url":null,"abstract":"Acute carbon monoxide poisoning (ACOP) is a cause of accidental or deliberate deaths worldwide. Subsequent complications, particularly delayed neurological sequelae (DNS), are preventable and treatable based on their pathophysiology. Hyperbaric oxygenation therapy (HBO) is a potential procedure for preventing and treating DNS; however, the effects of HBO on DNS are unclear and debated. In the present study, we investigated which factors are associated with the development of DNS and the effects of HBO in patients with ACOP. We performed retrospective subanalyses of the COP-J registry, focusing on adults who underwent HBO, regardless of whether they developed DNS. The multivariable analysis showed that the Glasgow coma scale (GCS) on admission was significantly associated with DNS (odds ratio 0.736; 95% confidence interval 0.608-0.892; P = 0.002). The receiver operating characteristic curve analysis of GCS for DNS revealed a cutoff value of 12.5 according to Youden's index (sensitivity 80.8%, specificity 76.9%). This retrospective analysis of a nationwide Japanese registry of ACOP showed that low GCS scores on admission could be a predictive factor for DNS, with a possible cutoff value of ≤12, in patients who undergo HBO.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"69-73"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080636","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

Anticancer agent doxorubicin toxicity to in vitro X. laevis tadpole organ heart and mature frog heart and liver mitochondria. 抗癌剂阿霉素对离体田鼠蝌蚪器官心脏和成熟蛙心脏、肝脏线粒体的毒性研究。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.333

Hideki Hanada, Seigo Sanoh, Keiko Kashiwagi, Akihiko Kashiwagi

{"title":"Anticancer agent doxorubicin toxicity to in vitro X. laevis tadpole organ heart and mature frog heart and liver mitochondria.","authors":"Hideki Hanada, Seigo Sanoh, Keiko Kashiwagi, Akihiko Kashiwagi","doi":"10.2131/jts.50.333","DOIUrl":"https://doi.org/10.2131/jts.50.333","url":null,"abstract":"One of the cancer drugs discharged into hospital wastewater, doxorubicin (DOX), is suspected of toxic effects on aquatic organisms. Cardiac and mitochondrial toxicity of DOX was investigated using cultured Xenopus (X.) laevis tadpole heart and mature frog liver mitochondria as materials. While 10-9 DOX was not found to suppress heart rate, 10-7 M DOX caused short-term heartbeat suppression in a preliminary experiment. Compared to the heart rate of untreated organ hearts kept in heart-organ medium without hydrogen-peroxide oxidoreductase enzyme catalase (CAT) for 9 days, that of 10-8 M DOX-treated hearts decreased over time. The heartbeat suppression was improved by adding CAT to the heart culture medium, suggesting that DOX induces reactive oxygen species (ROS) in cultured tadpole hearts. Mitochondrial swelling assay was conducted. DOX was found to suppress slight swelling of heart and liver mitochondria with adenosine triphosphate (ATP) treatment. DOX also suppressed Ca++-induced swelling of heart and liver mitochondria with ATP treatment. These findings suggest that the side effects of DOX on X. laevis heart and liver mitochondria are likely similar to those of cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPT) and also a ROS generator, leading to cardiac and mitochondrial dysfunction.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 7","pages":"333-342"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553832","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

An update on ototoxicity: from a genetic perspective. 耳毒性的最新进展：从遗传学角度看。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.245

Negar Akbari, Fatemeh Mahmoudi Lamooki, Mahmood Rezvani Amin, Seyyed Emran Disnad, Vahid Yousefinejad, Naeem Goharnia

引用次数: 0

Ginkgetin ameliorates IL-1β-stimulated inflammation via modulating PI3K/AKT/NF-κB cascade in human osteoarthritis chondrocytes. 银杏素通过调节人骨关节炎软骨细胞中PI3K/AKT/NF-κB级联，改善il -1β刺激的炎症。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.627

Guoping Yang, Xueli Zhang, Zhizhi Wang, Shengrong Bi

{"title":"Ginkgetin ameliorates IL-1β-stimulated inflammation via modulating PI3K/AKT/NF-κB cascade in human osteoarthritis chondrocytes.","authors":"Guoping Yang, Xueli Zhang, Zhizhi Wang, Shengrong Bi","doi":"10.2131/jts.50.627","DOIUrl":"https://doi.org/10.2131/jts.50.627","url":null,"abstract":"Osteoarthritis (OA) is a degenerative joint condition characterized by an increased density of the subchondral osseous tissue, cartilage degradation, and synovial membrane inflammation. Ginkgetin, a bioactive compound derived from Ginkgo biloba, exhibits notable anti-inflammatory properties in various disease models. In the current study, we aimed to determine the therapeutic potential of ginkgetin in mitigating IL-1β-induced inflammatory responses in human osteoarthritis chondrocytes. Our findings demonstrated that ginkgetin significantly inhibited the IL-1β-induced production of prostaglandin E2 (PGE2) and nitric oxide (NO). Additionally, ginkgetin downregulated the expression of IL-1β-induced proinflammatory mediators and cartilage-degrading enzymes. Furthermore, ginkgetin attenuated the degradation of key extracellular matrix components, including aggrecan and type II collagen. Mechanistically, ginkgetin exerted its protective effects by markedly suppressing the activation of the PI3K/AKT/NF-κB signaling pathway. Taken together, our findings demonstrated that ginkgetin ameliorates IL-1β-stimulated inflammation via modulation of the PI3K/AKT/NF-κB cascade, underscoring its viability as a promising therapeutic strategy for managing OA.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 11","pages":"627-636"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437765","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

Testosterone contributes sex differences of urinary biomarkers for nephrotoxicity in rats. 睾酮有助于大鼠肾毒性尿液生物标志物的性别差异。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.413

Satoshi Tsuji, Aya Hasegawa-Izaki, Bunichiro Ogawa, Hisaharu Yamada

{"title":"Testosterone contributes sex differences of urinary biomarkers for nephrotoxicity in rats.","authors":"Satoshi Tsuji, Aya Hasegawa-Izaki, Bunichiro Ogawa, Hisaharu Yamada","doi":"10.2131/jts.50.413","DOIUrl":"https://doi.org/10.2131/jts.50.413","url":null,"abstract":"Urinary biomarkers have been used widely in non-clinical toxicity studies to detect kidney dysfunction/injury caused by drugs under development. Although their usefulness to evaluate nephrotoxicity has been well studied, knowledge about sex differences in the urinary excretion levels of these biomarkers remains inadequate. We previously demonstrated the existence of sex differences in the excretion levels of urinary biomarkers and that these differences were associated with the endogenous testosterone levels. In this study, testosterone was repeatedly administered subcutaneously to female rats for 4 weeks along with male rats as a comparison control, to investigate how the blood levels of testosterone contribute to the sex differences in the urinary biomarker and renal cortical protein levels. The results showed that the urinary excretion of leucine aminopeptidase (LAP), gamma-glutamyltransferase (γ-GTP), cystatin C (Cys-C), liver-type fatty acid binding protein (L-FABP), and beta2-microglobulin (β2MG) were increased, and the urinary excretion of kidney injury molecule 1 (Kim-1) was decreased. The protein level of megalin, an endocytic receptor, in the renal cortex, was higher in female rats than in male rats, and testosterone treatment led to decrease in the level in the female rats. Our results suggest that the blood testosterone level might be responsible for the sex differences in the urinary excretion levels of low-molecular-weight proteins via regulating the expression level of megalin in the renal cortex.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 8","pages":"413-424"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775757","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

Estimation of intravenous TTC (TTCiv) for Extractables and Leachables (E&Ls) by applying a modifying factor based on blood concentration predicted using an open-source PBPK model. 应用基于开放源代码PBPK模型预测的血药浓度的修正因子估计静脉中可提取物和可浸出物（e&l）的TTC （TTCiv）

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.471

Tae Hayashi, Akira Kotaki, Asako Fukushima, Tomoko Kawamura, Naruo Katsutani, Takashi Yamada, Akihiko Hirose

{"title":"Estimation of intravenous TTC (TTCiv) for Extractables and Leachables (E&Ls) by applying a modifying factor based on blood concentration predicted using an open-source PBPK model.","authors":"Tae Hayashi, Akira Kotaki, Asako Fukushima, Tomoko Kawamura, Naruo Katsutani, Takashi Yamada, Akihiko Hirose","doi":"10.2131/jts.50.471","DOIUrl":"https://doi.org/10.2131/jts.50.471","url":null,"abstract":"Pharmaceutical manufacturing and storage processes pose the potential risk of chemicals migrating from the packaging materials into pharmaceuticals. These migrants, known as extractables and leachables (E&Ls), consist of various chemicals that may pose a risk to patients during therapeutic use. Although exposure to E&Ls via the intravenous route is of greater concern, there is almost no toxicity information for these chemicals to determine the Permitted Daily Exposure (PDE). The purpose of this study was to establish the Threshold of Toxicological Concern for intravenous route exposure (TTCiv) for risk management of E&Ls contained in pharmaceuticals. First, we derived the oral PDEs of 287 chemicals from a list of 923 known E&Ls. Then, the modifying factor (α) for estimating the intravenous PDE from each oral PDE was calculated based on the ratio of the predicted blood concentrations (area under the curve (AUC) and maximum blood concentration (Cmax)) after oral and intravenous administration using the Integrated Chemical Environment (ICE) PBPK model. Additionally, due to uncertainty of the predictions without bioavailability information, the intravenous PDE was calculated using modifying factor 3 based on the maximum value of the root mean square error (RMSE) reported in varification of the High-Throughput Toxicokinetics (HTTK) model. In conclusion, by analyzing the distribution of the intravenous PDE for 287 chemicals, we propose a TTCiv of 27 µg/day/human, based on the ratio of Cmax. Our route extrapolation approach could contribute to the establishment of scientifically valid TTCs for not only E&Ls, but also for other impurities without toxicity information.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 9","pages":"471-481"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959077","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

Dabrafenib stimulates autophagy in thyroid carcinoma cells via HMGB-1. Dabrafenib通过HMGB-1刺激甲状腺癌细胞自噬。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.273

Xu Wang, Dianchao Wu, Yongqiang Wang, Fengjuan Han, Xue Feng

{"title":"Dabrafenib stimulates autophagy in thyroid carcinoma cells via HMGB-1.","authors":"Xu Wang, Dianchao Wu, Yongqiang Wang, Fengjuan Han, Xue Feng","doi":"10.2131/jts.50.273","DOIUrl":"https://doi.org/10.2131/jts.50.273","url":null,"abstract":"Autophagy has been implicated in the pathophysiology of thyroid cancer and in determining the response of cancer cells to anticancer therapy. Dabrafenib, a BRAF inhibitor, has demonstrated efficacy and safety in several types of cancers. However, it is unknown whether Dabrafenib exerts a protective effect on autophagy in thyroid carcinoma cells. In the current study, our findings demonstrate that treatment with Dabrafenib reduced cell viability and promoted LDH release in SW579 thyroid carcinoma cells. Dabrafenib was then shown to promote autophagy by increasing the level of Beclin1 and the LC3-II/LC3-I ratio while reducing the level of p62. Additionally, exposure to Dabrafenib upregulated the expression of HMGB-1 at both mRNA and protein levels. Interestingly, silencing of HMGB-1 abrogated Dabrafenib-induced autophagy, suggesting that the effects of Dabrafenib are mediated by HMGB-1. Further study revealed that Dabrafenib activated the JAK1/STAT1 signaling pathway and that blockage of the JAK1/STAT1 signaling pathway with its inhibitor Pyridone 6 ameliorated Dabrafenib-induced HMGB-1 upregulation and autophagy, implicating the involvement of the JAK1/STAT1 signaling pathway in this process. Collectively, these findings demonstrate that Dabrafenib induces autophagy in thyroid carcinoma cells via the JAK1/STAT1/HMGB-1 axis. Notably, this effect occurs independently of BRAF V600E mutation status, suggesting a novel therapeutic mechanism.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 6","pages":"273-281"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199549","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

Successful multimodal treatment of venlafaxine overdose-induced catecholamine-refractory shock: a case report. 多模式治疗文拉法辛过量致儿茶酚胺难治性休克1例。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.547

Tomoaki Hayakawa, Akimasa Sanagawa, Kazuki Ohashi, Kazuki Kotoge, Ryohei Matsui, Tetsuya Tamura, Jun Monma-Otaki, Yoko Furukawa-Hibi, Tomonori Hattori

{"title":"Successful multimodal treatment of venlafaxine overdose-induced catecholamine-refractory shock: a case report.","authors":"Tomoaki Hayakawa, Akimasa Sanagawa, Kazuki Ohashi, Kazuki Kotoge, Ryohei Matsui, Tetsuya Tamura, Jun Monma-Otaki, Yoko Furukawa-Hibi, Tomonori Hattori","doi":"10.2131/jts.50.547","DOIUrl":"https://doi.org/10.2131/jts.50.547","url":null,"abstract":"Venlafaxine was the first serotonin/noradrenaline reuptake inhibitor used to treat major depressive disorders. Its overdose can cause cardiovascular toxicity and life-threatening cardiogenic shock. We present the case of a 48-year-old woman who experienced venlafaxine overdose-induced cardiogenic shock. Initial treatment included gastric lavage, blood purification therapy, and ventricular assist device use. The serum venlafaxine concentration was 21.4 μg/mL at 12-24 hr after ingestion, which subsequently decreased to 11.0 and 8.4 μg/mL after 1 and 2 days, respectively. This trend in blood concentration exhibited a biphasic elimination pattern. In addition to venlafaxine-induced cardiotoxicity, the patient exhibited peripheral vascular unresponsiveness to catecholamines. Notably, this vascular dysfunction resolved more rapidly than the cardiotoxic effects. Ultimately, the patient was transferred to a psychiatric ward without sequelae. Although venlafaxine overdose-induced cardiotoxicity has been reported, reports on the unresponsiveness of peripheral blood vessels to catecholamines remain lacking. In cases of venlafaxine overdose-induced cardiogenic shock, both left ventricular function may be impaired and peripheral blood vessels may also be unresponsive to catecholamines. Therefore, rapid initiation of extracorporeal life support and multimodal removal of venlafaxine tailored to the clinical situation may contribute to patient survival.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 10","pages":"547-554"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206862","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

Slow-releasing hydrogen sulfide donor GYY4137 induces epithelial-mesenchymal transition in A549 human lung adenocarcinoma cells. 缓释硫化氢供体GYY4137诱导A549人肺腺癌细胞上皮-间质转化

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.425

Miu Kajihara, Toshihiko Aki, Takeshi Funakoshi, Kana Unuma

引用次数: 0

Comprehensive molecular docking on the AlphaFold-predicted protein structure proteome: identifying target protein candidates for puberulic acid. 基于alphafold预测的蛋白质结构蛋白质组的综合分子对接：鉴定青春期少女酸的候选靶蛋白。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.309

Teppei Hayama, Rin Sugawara, Ryo Kamata, Masakazu Sekijima, Kazuki Takeda

{"title":"Comprehensive molecular docking on the AlphaFold-predicted protein structure proteome: identifying target protein candidates for puberulic acid.","authors":"Teppei Hayama, Rin Sugawara, Ryo Kamata, Masakazu Sekijima, Kazuki Takeda","doi":"10.2131/jts.50.309","DOIUrl":"https://doi.org/10.2131/jts.50.309","url":null,"abstract":"Identifying the molecular targets of toxic compounds remains a major challenge in toxicology, particularly when adverse effects occur in off-target organs and the mechanism of action is unknown. To address this issue, a comprehensive computational pipeline was developed to perform high-throughput molecular docking across the entire AlphaFold2-predicted structural proteome of representative organisms such as human and mouse, followed by enrichment analysis to estimate biological processes potentially affected by ligand binding. The pipeline was first evaluated using six known drug-target pairs. In several cases, the known targets were ranked between the top 2 and 250 proteins (top 0.009-1.15%) among more than 21,000 proteins, and displayed docking poses consistent with experimentally observed binding conformations. However, performance was limited for certain targets, such as carbonic anhydrase II with acetazolamide, where the binding pocket was broad, leading to inaccurate docking results. The pipeline was subsequently applied to puberulic acid, a compound suspected of causing severe nephrotoxicity. Screening identified sodium/myo-inositol cotransporter 2 (SLC5A11) as a high-affinity target in both human and mouse, suggesting a mechanism involving disruption of renal osmoregulation. Although docking scores represent only theoretical binding estimates and do not directly imply physiological effects, their distribution was independent of protein length and AlphaFold2 confidence scores (pLDDT), supporting the methodological robustness. This in silico framework enables hypothesis-driven identification of potential target proteins for toxicants or therapeutics and offers a useful tool for predictive toxicology, particularly when experimental data are limited. The pipeline is available at: https://github.com/toxtoxcat/reAlldock.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 7","pages":"309-324"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553833","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