Journal of Toxicological Sciences最新文献_第5页

Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons. 大鼠周围神经细胞类型对甲基汞细胞毒性敏感性的比较研究：背根神经节神经元的敏感性更高。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.241

Eiko Yoshida, Kazuhiro Aoki, Yu Sasaki, Hinako Izuhara, Tsutomu Takahashi, Yasuyuki Fujiwara, Tomoya Fujie, Ke Du, Komyo Eto, Yo Shinoda, Toshiyuki Kaji

{"title":"Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons.","authors":"Eiko Yoshida, Kazuhiro Aoki, Yu Sasaki, Hinako Izuhara, Tsutomu Takahashi, Yasuyuki Fujiwara, Tomoya Fujie, Ke Du, Komyo Eto, Yo Shinoda, Toshiyuki Kaji","doi":"10.2131/jts.49.241","DOIUrl":"https://doi.org/10.2131/jts.49.241","url":null,"abstract":"Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 5","pages":"241-248"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863254","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

Perinatal maternal exposure to high-dose sodium phenobarbital in the modified Comparative Thyroid Assay: no significant reduction in thyroid hormones in pups despite notable effects in dams. 在改良的比较甲状腺测定法中，围产期母体暴露于高剂量苯巴比妥钠：尽管对母体有显著影响，但幼崽体内的甲状腺激素没有明显减少。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.509

Hidenori Suto, Keiko Ogata, Kenta Minami, Akira Sato, Naruto Tomiyama, Tadashi Kosaka, Hitoshi Hojo, Naofumi Takahashi, Hiroaki Aoyama, Tomoya Yamada

{"title":"Perinatal maternal exposure to high-dose sodium phenobarbital in the modified Comparative Thyroid Assay: no significant reduction in thyroid hormones in pups despite notable effects in dams.","authors":"Hidenori Suto, Keiko Ogata, Kenta Minami, Akira Sato, Naruto Tomiyama, Tadashi Kosaka, Hitoshi Hojo, Naofumi Takahashi, Hiroaki Aoyama, Tomoya Yamada","doi":"10.2131/jts.49.509","DOIUrl":"https://doi.org/10.2131/jts.49.509","url":null,"abstract":"We propose a modified Comparative Thyroid Assay (CTA, USEPA) utilizing a smaller number of Sprague-Dawley rats (N=10/group) that assesses brain thyroid hormone (TH) concentrations and periventricular heterotopia while maintaining assay sensitivity. Our recent findings demonstrated that a prenatal test cohort of the modified CTA detected a dose-dependent decrease in maternal serum T3 (up to -26%) and T4 (up to -44%) with sodium phenobarbital (NaPB) exposure at 1000 ppm and 1500 ppm, equivalent to intakes of 60 and 84 mg/kg/day, respectively. On gestation day (GD) 20, fetuses exhibited reduced serum (-26%) and brain (-29%) TH concentrations, although these reductions were not dose dependent. The present study expanded the treatment in a postnatal test cohort, with maternal exposure to NaPB (81-93 mg/kg/day) from GD6 to lactation day (LD) 21. We assessed serum and brain TH concentrations, and periventricular heterotopia in pups on postnatal days (PND) 4, 21, and 28. While LD21 dams showed significant reductions in serum T3 (up to -34%) and T4 (up to -54%), the pups did not exhibit significant TH suppression or periventricular heterotopia at any test point. Instead, a compensatory increase in T4 was observed in serum and brain of PND21 pups. The present study confirmed that perinatal maternal exposure to high doses of NaPB leads to a moderate decrease in maternal TH concentrations; however, the exposure of maternal rats to a similar dose of NaPB did not significantly reduce serum or brain TH concentrations in their postnatal offspring.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 11","pages":"509-529"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576099","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

Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells. 使用表达 MRGPRX2 的细胞对与戊唑醇盐酸盐有关的组胺释放风险进行有效的体外评估。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.163

Eri Hamamura-Yasuno, Junzo Kinoshita, Koichi Goto, Kazunori Fujimoto, Michael Pignatello, Yoshimi Tsuchiya, Kazuhiko Mori

{"title":"Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells.","authors":"Eri Hamamura-Yasuno, Junzo Kinoshita, Koichi Goto, Kazunori Fujimoto, Michael Pignatello, Yoshimi Tsuchiya, Kazuhiko Mori","doi":"10.2131/jts.49.163","DOIUrl":"10.2131/jts.49.163","url":null,"abstract":"Mas-related G-protein-coupled receptor X2 (MRGPRX2), expressed on mast cells, is associated with drug-induced pseudo-allergic reactions. Although it is well known that there are differences of sensitivity between species in the pseudo-allergic reactions, no platform for evaluating a human risk of the pseudo-allergic reactions observed in nonclinical studies has been established. Valemetostat tosylate, developed as an anti-cancer drug, induced histamine release in a nonclinical study with dogs. The purpose of the current study was to identify the mechanism and assess the human risk of valemetostat-tosylate-induced histamine release using dog and human MRGPRX2-expressing cells. In an experiment with human or dog MRGPRX2-expressing cells, valemetostat tosylate caused activation of human and dog MRGPRX2. Importantly, the EC50 for dog MRGPRX2 was consistent with the Cmax value at which histamine release was observed in dogs. Furthermore, the EC50 for human MRGPRX2 was ca. 27-fold higher than that for dog MRGPRX2, indicating a species difference in histamine-releasing activity. In a clinical trial, histamine release was not observed in patients receiving valemetostat tosylate. In conclusion, an in vitro assay using human and animal MRGPRX2-expressing cells would be an effective platform to investigate the mechanism and predict the human risk of histamine release observed in nonclinical studies.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 4","pages":"163-174"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331803","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

Simultaneous analysis of caffeine and paraxanthine provides potentially useful indexes in the treatment of acute caffeine intoxication. 同时分析咖啡因和副黄嘌呤为治疗急性咖啡因中毒提供了潜在的有用指标。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.447

Yoshitaka Yamazaki, Asuka Kaizaki-Mitsumoto, Mariko Sato, Yumiko Inoue, Kazuyuki Miyamoto, Keisuke Suzuki, Munetaka Hayashi, Kenji Dohi, Satoshi Numazawa

{"title":"Simultaneous analysis of caffeine and paraxanthine provides potentially useful indexes in the treatment of acute caffeine intoxication.","authors":"Yoshitaka Yamazaki, Asuka Kaizaki-Mitsumoto, Mariko Sato, Yumiko Inoue, Kazuyuki Miyamoto, Keisuke Suzuki, Munetaka Hayashi, Kenji Dohi, Satoshi Numazawa","doi":"10.2131/jts.49.447","DOIUrl":"https://doi.org/10.2131/jts.49.447","url":null,"abstract":"Caffeine (CFF) is efficiently absorbed after ingestion, and approximately 80% of ingested CFF is metabolized to paraxanthine (PXT). Although PXT has approximately twice the adenosine receptor antagonist activity of CFF, there are few reports measuring the metabolite concentrations during CFF intoxication. Furthermore, no studies have examined the efficacy of hemodialysis (HD) on PXT or the indicators that contribute to treatment strategies for patients with acute CFF intoxication. This study analyzed the association between CFF and PXT blood levels, the blood biochemical data, and the vital signs of 27 cases with information on CFF intake and elapsed time data. It was found that HD was not as effective as CFF against PXT in CFF intoxication; however, HD was effective in cases with relatively high PXT concentrations (>10 μg/mL). Simultaneous analysis of CFF and PXT would make it possible to estimate the time elapsed from CFF intake and the risk of hyperCKemia, which may develop in cases left untreated for a prolonged period after ingestion. Therefore, the measurement of PXT, in addition to CFF, is expected to provide useful information for understanding the pathogenesis of CFF intoxication and the development of treatment strategies of acute CFF intoxication.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 10","pages":"447-457"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365664","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

Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis. 利用机器学习和心率变异性分析预测非人灵长类动物药物诱发惊厥的新方法。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.231

Kazuhiro Kuga, Motohiro Shiotani, Kentaro Hori, Hiroshi Mizuno, Yusaku Matsushita, Harushige Ozaki, Kohei Hayashi, Takatomi Kubo, Manabu Kano

{"title":"Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis.","authors":"Kazuhiro Kuga, Motohiro Shiotani, Kentaro Hori, Hiroshi Mizuno, Yusaku Matsushita, Harushige Ozaki, Kohei Hayashi, Takatomi Kubo, Manabu Kano","doi":"10.2131/jts.49.231","DOIUrl":"https://doi.org/10.2131/jts.49.231","url":null,"abstract":"Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 5","pages":"231-240"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874720","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

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

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