Journal of Toxicological Sciences最新文献_第10页

Dexmedetomidine protects against Ropivacaine-induced neuronal pyroptosis via the Nrf2/HO-1 pathway. 右美托咪定通过Nrf2/HO-1途径保护罗哌卡因诱导的神经元焦亡。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.139

Run Wang, Pengfei Liu, Fan Li, Hui Qiao

{"title":"Dexmedetomidine protects against Ropivacaine-induced neuronal pyroptosis via the Nrf2/HO-1 pathway.","authors":"Run Wang, Pengfei Liu, Fan Li, Hui Qiao","doi":"10.2131/jts.48.139","DOIUrl":"https://doi.org/10.2131/jts.48.139","url":null,"abstract":"Dexmedetomidine (DEX) has been demonstrated to protect against ropivacaine (Ropi)-induced neuronal damages. This study was conducted to explore the protective role of DEX in Ropi-induced neuronal pyroptosis and provide a strategy to eliminate Ropi-induced neurotoxicity. The impacts of different concentrations of Ropi and DEX on neurotoxicity in SK-N-SH cells were evaluated by cell counting kit-8 assay and lactic dehydrogenase assay kits. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NLR family pyrin domain containing 3 (NLRP3), cleaved Caspase-1, cleaved N-terminal gasdermin D, interleukin (IL)-1β, and IL-18 were measured by real-time quantitative PCR, Western blotting, and enzyme linked immunosorbent assay. The Nrf2 level after nuclear/cytoplasmic separation was quantified. SK-N-SH cells were treated with si-Nrf2, Nigericin (NLRP3 activator), and Zinc Protoporphyrin (HO-1 inhibitor) to validate the mechanism. Ropi reduced SK-N-SH cell viability in a concentration- and time-dependent manner. DEX treatment alleviated Ropi-induced toxicity and inhibited pyroptosis. Ropi increased the expression levels of Nrf2 and HO-1, and DEX further enhanced the increases and promoted Nrf2 nuclear translocation. Nrf2/HO-1 inhibition or NLRP3 activation both neutralized the inhibitory role of DEX in Ropi-induced pyroptosis of SK-N-SH cells. Overall, DEX promoted the Nrf2/HO-1 pathway to inhibit NLRP3 expression, thus alleviating Ropi-induced neuronal pyroptosis.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 3","pages":"139-148"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10846639","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: 1

N-acetyl cysteine inhibits IL-1α release from murine keratinocytes induced by 2-hydroxyethyl methacrylate. N-乙酰半胱氨酸抑制甲基丙烯酸2-羟基乙酯诱导的小鼠角质形成细胞IL-1α的释放。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.557

Takahiro Kaji, Toshinobu Kuroishi, Kanan Bando, Masatoshi Takahashi, Shunji Sugawara

{"title":"N-acetyl cysteine inhibits IL-1α release from murine keratinocytes induced by 2-hydroxyethyl methacrylate.","authors":"Takahiro Kaji, Toshinobu Kuroishi, Kanan Bando, Masatoshi Takahashi, Shunji Sugawara","doi":"10.2131/jts.48.557","DOIUrl":"10.2131/jts.48.557","url":null,"abstract":"The hydrophilic compound 2-hydroxyethyl methacrylate (HEMA) is a major component of dental bonding materials, and it enhances the binding of resin-composites to biomolecules. However, HEMA is a well-known contact sensitizer. We reported previously that intradermal injection of HEMA induces the production of IL-1 locally in the skin. Keratinocytes are the first barrier against chemical insults and constitutively express IL-1α. In this study, we analyzed whether HEMA induces the production of inflammatory cytokines from murine keratinocyte cell line Pam212 cells. We demonstrated that HEMA induced the release of 17-kDa mature IL-1α and caused cytotoxicity. The activity of calpain, an IL-1α processing enzyme, was significantly higher in HEMA-treated cells. The thiol-containing antioxidant N-acetyl cysteine (NAC) inhibited HEMA-induced IL-1α release but not cytotoxicity. NAC inhibited intracellular calpain activity and reactive oxygen species (ROS) production induced by HEMA. NAC post-treatment also inhibited IL-1α release and intracellular ROS production induced by HEMA. Furthermore, HEMA-induced in vivo inflammation also inhibited by NAC. NAC inhibited polymerization of HEMA through adduct formation via sulfide bonds between the thiol group of NAC and the reactive double bond of HEMA. HEMA-induced IL-1α release and cytotoxicity were also inhibited if HEMA and NAC were pre-incubated before adding to the cells. These results suggested that NAC inhibited IL-1α release through decreases in intracellular ROS and the adduct formation with HEMA. We concluded that HEMA induces IL-1α release from skin keratinocytes, and NAC may be a promising candidate as a therapeutic agent against inflammation induced by HEMA.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 10","pages":"557-569"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125709","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

Benzo(a)pyrene-induced mitochondrial respiration and glycolysis disturbance in human neuroblastoma cells. 苯并(a)芘诱导人神经母细胞瘤细胞线粒体呼吸和糖酵解紊乱。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.87

Yi Lyu, Jin Yang, LiXia Cheng, ZhaoFei Li, JinPing Zheng

{"title":"Benzo(a)pyrene-induced mitochondrial respiration and glycolysis disturbance in human neuroblastoma cells.","authors":"Yi Lyu, Jin Yang, LiXia Cheng, ZhaoFei Li, JinPing Zheng","doi":"10.2131/jts.48.87","DOIUrl":"https://doi.org/10.2131/jts.48.87","url":null,"abstract":"Mammalian cells generate ATP through mitochondrial respiration and glycolysis. Mitochondria not only play a key role in cell energy metabolism but also in cell cycle regulation. As a neurotoxic pollutant, benzo(a)pyrene (BaP) can trigger neuronal oxidative damage and apoptosis. However, the features of BaP-induced energy metabolism disturbance in SH-SY5Y cells has rarely been addressed. This study aimed to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as indications of respiratory activities and glycolytic. SH-SY5Y cells were treated with BaP to establish a cytotoxicity model, and butylated hydroxy anisole (BHA) was used to alleviate the damages induced by BaP. Using the Seahorse Extracellular Flux analyzer (XFp), we found that BaP significantly reduced basal respiration, ATP-linked OCR in SH-SY5Y cells with dose- and time-dependent. BHA supplementation recovered the mitochondrial respiration, synchronously attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers, then rescued BaP-induced cell apoptosis. But long-term exposure to BaP or exposure to a high dosage of BaP could decrease OCR associated with maximal respiratory, spare capacity, and glycolysis metabolism. At the same time, the damage to cells is also more severe with the rate of apoptosis and mitochondrial membrane potential (ΔΨm) loss rising sharply, which were not entirely reversed by BHA. This study provides energy metabolism-related, indicative biomarkers of cytotoxicity induced by BaP, which might provide information for early prevention and intervention.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 2","pages":"87-97"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10660331","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: 1

Tributyltin activates the Keap1-Nrf2 pathway via a macroautophagy-independent reduction in Keap1. 三丁基锡通过Keap1的巨噬非依赖性减少激活Keap1- nrf2途径。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.161

Misaki Hatano, Shunichi Hatamiya, Masatsugu Miyara, Yaichiro Kotake

{"title":"Tributyltin activates the Keap1-Nrf2 pathway via a macroautophagy-independent reduction in Keap1.","authors":"Misaki Hatano, Shunichi Hatamiya, Masatsugu Miyara, Yaichiro Kotake","doi":"10.2131/jts.48.161","DOIUrl":"https://doi.org/10.2131/jts.48.161","url":null,"abstract":"Tributyltin (TBT) is an environmental chemical, which was used as an antifouling agent for ships. Although its use has been banned, it is still persistently present in ocean sediments. Although TBT reportedly causes various toxicity in mammals, few studies on the mechanisms of biological response against TBT toxicity exist. The well-established Keap1-Nrf2 pathway is activated as a cytoprotective mechanism under stressful conditions. The relationship between TBT and the Keap1-Nrf2 pathway remains unclear. In the present study, we evaluated the effect of TBT on the Keap1-Nrf2 pathway. TBT reduced Keap1 protein expression in Neuro2a cells, a mouse neuroblastoma cell line, after 6 hr without altering mRNA expression levels. TBT also promoted the nuclear translocation of Nrf2, a transcription factor for antioxidant proteins, after 12 hr and augmented the expression of heme oxygenase 1, a downstream protein of Nrf2. Furthermore, TBT decreased Keap1 levels in mouse embryonic fibroblast (MEF) cells, with the knockout of Atg5, which is essential for macroautophagy, as well as in wild-type MEF cells. These results suggest that TBT activates the Keap1-Nrf2 pathway via the reduction in the Keap1 protein level in a macroautophagy-independent manner. The Keap1-Nrf2 pathway is activated by conformational changes in Keap1 induced by reactive oxygen species or electrophiles. Furthermore, any unutilized Keap1 protein is degraded by macroautophagy. Understanding the novel mechanism governing the macroautophagy-independent reduction in Keap1 by TBT may provide insights into the unresolved biological response mechanism against TBT toxicity and the activation mechanism of the Keap1-Nrf2 pathway.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 3","pages":"161-168"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10846634","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: 1

Neuro-protective effects of n-butylphthalide on carbon monoxide poisoning rats by modulating IL-2, AKT and BCL-2. 正丁苯酞通过调节IL-2、AKT和BCL-2对一氧化碳中毒大鼠的神经保护作用。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.495

Shengtao Tang, Kunyu Wang, Xiaokun Qi

{"title":"Neuro-protective effects of n-butylphthalide on carbon monoxide poisoning rats by modulating IL-2, AKT and BCL-2.","authors":"Shengtao Tang, Kunyu Wang, Xiaokun Qi","doi":"10.2131/jts.48.495","DOIUrl":"https://doi.org/10.2131/jts.48.495","url":null,"abstract":"Acute carbon monoxide poisoning (CO-poisoning) causes neurotoxicity by inducing necrosis, apoptosis, lipid peroxidation, and oxidative stress. DL-3-n-butylphthalide (NBP) is a synthetic compound originally extracted from the seeds of Chinese celery and based on pure l-3-n-butylphthalide. In ischemia/reperfusion, it exerts neuroprotective effects through its anti-apoptotic, anti-necrotic and antioxidant properties, and activation of pro-survival pathways. Our study performed bioinformatic analysis to identify the differential expression genes. CO-poisoning patients' blood was collected to confirm the findings. Male rats were exposed to CO 3000 ppm for 40 min, and NBP (100 mg/kg/day) was continuously injected intraperitoneally immediately after poisoning and for the next 15 days. After NBP treatment, the rats were evaluated by Morris water maze test. At the end of experiments, blood and brain tissues of the rats were collected to evaluate the expression levels of IL-2, AKT and BCL-2. We found that IL-2 was elevated in CO-poisoning patients and animal models. Brain tissue damage in CO-poisoning rats was significantly alleviated after NBP treatment. Furthermore, NBP increased the expression of IL-2, AKT and BCL-2 in rat CO-poisoning model. NBP showed neuroprotective action by increasing IL-2, AKT, and BCL-2 expressions.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 9","pages":"495-505"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148831","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

Establishment of an in vitro cholestasis risk assessment system using two-dimensional cultured HepaRG cells and 12 bile acids. 利用二维培养HepaRG细胞和12种胆汁酸建立体外胆汁淤积风险评估体系。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.47

Toshihisa Koga, Kenji Takeuchi, Ken Umehara

{"title":"Establishment of an in vitro cholestasis risk assessment system using two-dimensional cultured HepaRG cells and 12 bile acids.","authors":"Toshihisa Koga, Kenji Takeuchi, Ken Umehara","doi":"10.2131/jts.48.47","DOIUrl":"https://doi.org/10.2131/jts.48.47","url":null,"abstract":"Drug-induced liver injury (DILI) is a major cause of market withdrawal or drug-development discontinuation because of safety concerns. In this study, we focused on drug-induced cholestasis (DIC) to establish an in vitro cytotoxicity test system and analyze its sensitivity using two-dimensional (2-D) cultured HepaRG cells and 12 types of bile acids (BAs) present in the human serum. First, to detect the cytotoxicity associated with cholestasis effectively, non-toxic BA concentrations were investigated and determined to be 100-fold the human serum value (455 μM total BAs). Next, the cytotoxicity of 31 compounds that can inhibit the bile acid export pump (BSEP) and were categorized as no-DILI-concern, less-DILI-concern, and most-DILI-concern was examined. None of the no-DILI-concern compounds yielded cytotoxicity, whereas almost all less-DILI-concern compounds (with the exception of simvastatin) and most-DILI-concern compounds (with the exception of bosentan) exhibited cytotoxicity. An investigation of the cause of cytotoxicity using 3H-taurocholic acid revealed that most-DILI-concern and less-DILI-concern compounds, but not no-DILI-concern compounds, triggered the accumulation of radioactivity in the cell lysates. Thus, the onset of cytotoxicity seemed to be associated with cholestasis. The established HepaRG cytotoxicity assessment system (sensitivity of 89%, specificity of 100%, and accuracy of 97%) was mostly superior to the Css/BSEP IC50 (> 0.1) assessment system (sensitivity of 83%, specificity of 100%, and accuracy of 72%). Therefore, the assay method using 2-D cultured HepaRG cells and 12 BAs established here can be widely applicable as a model for the in vitro potential assessment of DIC.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 1","pages":"47-56"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489523","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

Melatonin therapy reverses lead exposure-induced testicular damage in rats despite the lack of effect on serum testosterone levels. 褪黑素治疗可以逆转铅暴露引起的大鼠睾丸损伤，尽管对血清睾酮水平没有影响。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.481

Marco A Gallegos-Reyes, Alejandro R Antaño-Martínez, Yolanda Alcaraz-Contreras, Jorge A Alegría-Torres, Juvencio Robles, Eunice Yáñez-Barrientos, Minerva Martinez-Alfaro

{"title":"Melatonin therapy reverses lead exposure-induced testicular damage in rats despite the lack of effect on serum testosterone levels.","authors":"Marco A Gallegos-Reyes, Alejandro R Antaño-Martínez, Yolanda Alcaraz-Contreras, Jorge A Alegría-Torres, Juvencio Robles, Eunice Yáñez-Barrientos, Minerva Martinez-Alfaro","doi":"10.2131/jts.48.481","DOIUrl":"https://doi.org/10.2131/jts.48.481","url":null,"abstract":"Lead (Pb) exposure induces testicular damage and infertility. The aim of this study was to analyze and compare the therapeutic effects of antioxidants or vitamin D and calcium, which have previously been shown to reduce the toxic effects of Pb co-exposure, in rats. Rats were exposed to Pb for 28 days and subsequently treated with antioxidant (melatonin, silymarin), vitamin D and calcium (VitDCa) or a combination (melatonin or silymarin with VitDCa) for 28 days. Control groups included untreated rats (no Pb exposure or therapy), rats exposed only to melatonin or silymarin and rats exposed to Pb without post exposure therapy. Pb exposure induced testicular damage, increased blood lead level (BLL) and reduced serum testosterone level (STL). Rats exposed to Pb and left untreated for 28 days showed persistent pathological testicular alterations. The two treatments that were most effective in reversing pathological testis damage and restoring spermatogenesis were melatonin and silymarin. However, silymarin and melatonin treatment resulted in significantly different serum testosterone levels in rats. Whereas melatonin therapy reduced serum testosterone to levels lower than those in control rats, silymarin increased serum testosterone to levels higher than those in controls. Our pathological analysis of testes revealed that melatonin promoted spermatogenesis and regression of Pb exposure-induced degenerative changes, despite the associated reduction in serum testosterone levels. This result suggests that circulating testosterone may not have an important role in spermatogenesis. Collectively, our results suggest that melatonin and silymarin are effective therapies against the toxic effects Pb exposure in the male reproductive system.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 8","pages":"481-486"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9935354","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

Proteasome and p62/SQSTM1 are involved in methylmercury toxicity mitigation in mouse embryonic fibroblast cells. 蛋白酶体和p62/SQSTM1参与小鼠胚胎成纤维细胞甲基汞毒性的缓解。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.355

Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Ohshiro, Shimpei Uraguchi, Masako Kiyono

{"title":"Proteasome and p62/SQSTM1 are involved in methylmercury toxicity mitigation in mouse embryonic fibroblast cells.","authors":"Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Ohshiro, Shimpei Uraguchi, Masako Kiyono","doi":"10.2131/jts.48.355","DOIUrl":"https://doi.org/10.2131/jts.48.355","url":null,"abstract":"Methylmercury (MeHg), an environmental pollutant, disrupts and impairs cellular function. MeHg binds to various cellular proteins, causing dysfunction and misfolding, which are considered underlying causes of MeHg toxicity. The p62 protein, also termed SQSTM1, is a ubiquitin-binding protein that targets ubiquitinated substrates to undergo autophagy and plays a key role in ameliorating MeHg toxicity. p62 also delivers ubiquitinated substrates to proteasomes. However, the role of these degradation systems in mitigating MeHg toxicity remains unknown. Herein, we explored the impact of the proteasome inhibitor MG132 on MeHg toxicity and examined the toxicity of co-treatment with MG132 and MeHg in p62KO mouse embryonic fibroblasts (MEFs) by analyzing cell viability, immunoblotting, mRNA levels, immunofluorescence, and the mercury content. The proteasome inhibitor MG132 enhanced MeHg-induced cytotoxicity while reducing intracellular mercury levels in MEFs. Co-treatment with MG132 and MeHg markedly increased levels of p62 and ubiquitinated proteins. Furthermore, co-treatment with MG132 and MeHg reduced p62KO MEF viability compared to that of wild-type MEFs. Our findings suggest that the proteasome participates in mitigating MeHg cytotoxicity, while p62 may play an important role in transporting MeHg-induced ubiquitinated proteins to the proteasome, as well as in autophagy. Collectively, these results imply that p62, and proteasome, and autophagy are vital for cytoprotection against MeHg toxicity.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 6","pages":"355-361"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9618277","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: 1

A case of pulmonary edema due to guanfacine intoxication with measurement of serum guanfacine concentrations. 胍法辛中毒肺水肿1例与血清胍法辛浓度测定。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.641

Ryo Ayata, Motoki Fujita, Kayoko Harada, Yusuke Esaki, Yasutaka Koga, Yukari Hisamoto, Maki Asami-Noyama, Saki Takeda, Kazuki Harada, Ryosuke Tsuruta

{"title":"A case of pulmonary edema due to guanfacine intoxication with measurement of serum guanfacine concentrations.","authors":"Ryo Ayata, Motoki Fujita, Kayoko Harada, Yusuke Esaki, Yasutaka Koga, Yukari Hisamoto, Maki Asami-Noyama, Saki Takeda, Kazuki Harada, Ryosuke Tsuruta","doi":"10.2131/jts.48.641","DOIUrl":"10.2131/jts.48.641","url":null,"abstract":"Guanfacine hydrochloride extended-release (GXR) is used to treat attention deficit hyperactivity disorder. It is a selective α2A-adrenorecepor agonist that was reported to cause QT prolongation and hypotension in the event of overdosing. We report the case of a 17-year-old man who took 226 tablets of GXR 3 mg for attempted suicide. He was found complaining of dyspnea, and emergency medical services were called. When the patient was transferred to our hospital, his Glasgow coma scale was 12 (E4V3M5). He was agitated and hypoxemic. He was intubated for invasive mechanical ventilation under sedation. His chest X-ray and computed tomography scan showed pulmonary edema. Transthoracic echocardiography showed markedly reduced cardiac function. His serum guanfacine concentration peaked on day 3 after admission. His pulmonary edema improved quickly after a decrease in serum guanfacine concentration, but cardiac decompensation persisted for about 1 month. This case reveals that the decline in cardiac function after guanfacine intoxication is prolonged even after its serum concentration has decreased.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 12","pages":"641-644"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478094","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

Effects of early-life tosufloxacin tosilate hydrate administration on growth rate, neurobehavior, and gut microbiota at adulthood in male mice. 幼年给药tosuflo沙星tosilate hydrate对成年雄性小鼠生长速度、神经行为和肠道微生物群的影响。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2023-01-01 DOI: 10.2131/jts.48.149

Ayano Hasegawa, Takahiro Sasaki, Jahidul Islam, Takashi Tominaga, Tomonori Nochi, Kenshiro Hara, Kentaro Tanemura

{"title":"Effects of early-life tosufloxacin tosilate hydrate administration on growth rate, neurobehavior, and gut microbiota at adulthood in male mice.","authors":"Ayano Hasegawa, Takahiro Sasaki, Jahidul Islam, Takashi Tominaga, Tomonori Nochi, Kenshiro Hara, Kentaro Tanemura","doi":"10.2131/jts.48.149","DOIUrl":"https://doi.org/10.2131/jts.48.149","url":null,"abstract":"Reportedly, antibiotics, which are frequently prescribed in children, have long-term effects owing to gut microbiota dysregulation. Tosufloxacin tosilate hydrate (TFLX) is the first orally administered new quinolone with high efficacy and broad-spectrum action approved as an antibacterial agent for pediatric use in Japan. However, studies on the effects of its early-stage administration are limited. Therefore, we aimed to analyze the later effects of its developmental administration by monitoring growth rate, neurobehavior, and gut microbiota in mice. The TFLX was administered via drinking water at a dose of up to 300 mg/kg for two consecutive weeks during the developmental period (4-6 weeks of age) or adulthood (8-10 weeks of age). Thereafter, the body weights of the mice were measured weekly to monitor growth rate. Behavioral tests were also conducted on 11-12-week-old mice to examine the neurobehavioral effects of the treatment. Further, to examine the effects of the treatment on microbiota, fecal samples were collected from the rectum of mice dissected at 12 weeks of age, and 16s rRNA analysis was conducted. Our results showed increased body weights after TFLX administration, without any long-term effects. Behavioral analysis suggested alterations in anxiety-like behaviors and memory recall dysregulation, and gut microbiota analysis revealed significant differences in bacterial composition. These findings indicated that TFLX administration during the developmental period affects mice growth rate, neurobehavior, and gut microbiota structure. This is the first study to report that TFLX is potentially associated with the risk of long effects.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"48 3","pages":"149-159"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10829220","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