Pub Date : 2024-01-02DOI: 10.1007/s43188-023-00219-8
Gyu-Hyeong Lee, V. Kim, Sung-Gyu Lee, Eunseo Jeong, Changmin Kim, Yoo-Bin Lee, Donghak Kim
{"title":"Catalytic enhancements in cytochrome P450 2C19 by cytochrome b_5","authors":"Gyu-Hyeong Lee, V. Kim, Sung-Gyu Lee, Eunseo Jeong, Changmin Kim, Yoo-Bin Lee, Donghak Kim","doi":"10.1007/s43188-023-00219-8","DOIUrl":"https://doi.org/10.1007/s43188-023-00219-8","url":null,"abstract":"","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"13 7","pages":"1-8"},"PeriodicalIF":2.3,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139124694","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}
Pub Date : 2023-12-13DOI: 10.1007/s43188-023-00218-9
D. H. Cha, G. Kim, Rahul U. Nepal, M. Nepal, Tae Cheon Jeong
{"title":"A convenient spectrophotometric test for screening skin-sensitizing chemicals using reactivity with glutathione in chemico","authors":"D. H. Cha, G. Kim, Rahul U. Nepal, M. Nepal, Tae Cheon Jeong","doi":"10.1007/s43188-023-00218-9","DOIUrl":"https://doi.org/10.1007/s43188-023-00218-9","url":null,"abstract":"","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"23 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139005705","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}
Pub Date : 2023-11-23DOI: 10.1007/s43188-023-00216-x
S. Lee, Sang-Yong Eom, Ji-Ae Lim, Byung-Sun Choi, Ho-Jang Kwon, Young-Seoub Hong, Yong-Dae Kim, Heon Kim, J. Park
{"title":"Association between urinary arsenic concentration and genetic polymorphisms in Korean adults","authors":"S. Lee, Sang-Yong Eom, Ji-Ae Lim, Byung-Sun Choi, Ho-Jang Kwon, Young-Seoub Hong, Yong-Dae Kim, Heon Kim, J. Park","doi":"10.1007/s43188-023-00216-x","DOIUrl":"https://doi.org/10.1007/s43188-023-00216-x","url":null,"abstract":"","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"130 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139243455","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}
Pub Date : 2023-11-14DOI: 10.1007/s43188-023-00213-0
Renata Kuraś, Maciej Stępnik, Jarosław Grobelny, Emilia Tomaszewska, Magdalena Stanisławska, Katarzyna Domeradzka-Gajda, Wojciech Wąsowicz, Beata Janasik
Abstract There is still little literature data on the toxicity and safety of the commonly used molybdenum (Mo) disulfide which is present in the working as well as living environments. Thus, an experiment was carried out involving rats, with single and repeated intratracheal exposure (in the latter case, 7 administrations at 2-week intervals with the analysis performed after 90 days) to lower (1.5 mg Mo kg −1 b.w.) and higher (5 mg Mo kg −1 b.w.) doses of molybdenum(IV) sulfide nanoparticles (MoS 2 -NPs) and microparticles (MoS 2 -MPs). The analysis of Mo concentrations in the tail and heart blood as well as in soft tissues (lung, liver, spleen, brain), after mineralization and bioimaging, was meant to facilitate an assessment of its accumulation and potential effects on the body following short- and long-term exposure. The multi-compartment model with an exponential curve of Mo concentration over time with different half-lives for the distribution and elimination phases of MoS 2 -MPs and MoS 2 -NPs was observed. After 24 h of exposure, a slight increase in Mo concentration in blood was observed. Next, Mo concentration indicated a decrease in blood concentration from 24 h to day 14 (the Mo concentration before the second administration), below the pre-exposure concentration. The next phase was linear, less abrupt and practically flat, but with an increasing trend towards the end of the experiment. Significantly higher Mo concentrations in MoS 2 -NPs and MoS 2 -MPs was found in the lungs of repeatedly exposed rats compared to those exposed to a single dose. The analysis of Mo content in the liver and the spleen tissue showed a slightly higher concentration for MoS 2 -NPs compared to MoS 2 -MPs. The results for the brain were below the calculated detection limit. Results were consistent with results obtained by bioimaging technique.
摘要目前，关于常用的二硫化钼(Mo)在工作和生活环境中的毒性和安全性的文献资料还很少。因此，对大鼠进行了一项实验，通过单次和多次气管内暴露(后者为7次，间隔2周，90天后进行分析)，以降低(1.5 mg Mo kg - 1 b.w)和更高(5 mg Mo kg - 1 b.w)剂量的钼(IV)硫化钼纳米颗粒(MoS 2 -NPs)和微粒(MoS 2 -MPs)。矿化和生物成像后，对尾血和心脏血液以及软组织(肺、肝、脾、脑)中的Mo浓度进行分析，旨在促进评估其积累和短期和长期暴露后对身体的潜在影响。观察到Mo 2 -MPs和Mo 2 -NPs的分布和消除相具有不同半衰期Mo浓度随时间的指数曲线的多室模型。暴露24 h后，血液中Mo浓度略有升高。其次，Mo浓度显示血药浓度从24小时到第14天(第二次给药前的Mo浓度)下降，低于暴露前的浓度。下一阶段是线性的，不那么突然，几乎是平坦的，但在实验结束时有增加的趋势。与单次暴露大鼠相比，反复暴露大鼠肺部的MoS 2 -NPs和MoS 2 -MPs中的Mo浓度明显较高。肝脏和脾脏组织Mo含量分析显示，MoS 2 -NPs的浓度略高于MoS 2 -MPs。对大脑的检测结果低于计算出的检测限。结果与生物成像技术结果一致。
{"title":"Distribution of molybdenum in soft tissues and blood of rats after intratracheal instillation of molybdenum(IV) sulfide nano- and microparticles","authors":"Renata Kuraś, Maciej Stępnik, Jarosław Grobelny, Emilia Tomaszewska, Magdalena Stanisławska, Katarzyna Domeradzka-Gajda, Wojciech Wąsowicz, Beata Janasik","doi":"10.1007/s43188-023-00213-0","DOIUrl":"https://doi.org/10.1007/s43188-023-00213-0","url":null,"abstract":"Abstract There is still little literature data on the toxicity and safety of the commonly used molybdenum (Mo) disulfide which is present in the working as well as living environments. Thus, an experiment was carried out involving rats, with single and repeated intratracheal exposure (in the latter case, 7 administrations at 2-week intervals with the analysis performed after 90 days) to lower (1.5 mg Mo kg −1 b.w.) and higher (5 mg Mo kg −1 b.w.) doses of molybdenum(IV) sulfide nanoparticles (MoS 2 -NPs) and microparticles (MoS 2 -MPs). The analysis of Mo concentrations in the tail and heart blood as well as in soft tissues (lung, liver, spleen, brain), after mineralization and bioimaging, was meant to facilitate an assessment of its accumulation and potential effects on the body following short- and long-term exposure. The multi-compartment model with an exponential curve of Mo concentration over time with different half-lives for the distribution and elimination phases of MoS 2 -MPs and MoS 2 -NPs was observed. After 24 h of exposure, a slight increase in Mo concentration in blood was observed. Next, Mo concentration indicated a decrease in blood concentration from 24 h to day 14 (the Mo concentration before the second administration), below the pre-exposure concentration. The next phase was linear, less abrupt and practically flat, but with an increasing trend towards the end of the experiment. Significantly higher Mo concentrations in MoS 2 -NPs and MoS 2 -MPs was found in the lungs of repeatedly exposed rats compared to those exposed to a single dose. The analysis of Mo content in the liver and the spleen tissue showed a slightly higher concentration for MoS 2 -NPs compared to MoS 2 -MPs. The results for the brain were below the calculated detection limit. Results were consistent with results obtained by bioimaging technique.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"25 14","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134991641","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}
Pub Date : 2023-10-05DOI: 10.1007/s43188-023-00212-1
Jong-Yeon Kim, Yooheon Park, Seok-Hee Lee, Eun‐Jung Park, Hae‐Jeung Lee
{"title":"Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens","authors":"Jong-Yeon Kim, Yooheon Park, Seok-Hee Lee, Eun‐Jung Park, Hae‐Jeung Lee","doi":"10.1007/s43188-023-00212-1","DOIUrl":"https://doi.org/10.1007/s43188-023-00212-1","url":null,"abstract":"","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134975986","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}
Pub Date : 2023-10-03DOI: 10.1007/s43188-023-00204-1
Marwa Monier Mahmoud Refaie, Sayed Shehata, Maram El-Hussieny, Michael Atef Fawzy, Nagwa Zenhom Mustafa Ahmed, Heba Marey, Asmaa Mohammed Hishmat, Turki Alkully, Eman Shaaban Mahmoud Abd El Rahman
Abstract One of the commoly used chemotherapeutic agents is 5-Fluorouracil (5-FU). Unfortunately, the clinical administration of 5-FU is complicated with serious cardiotoxic effects and the safe use becomes an urgent task in cardio-oncology. Till now, there are no studies discussed the role of empagliflozin (EMP) against 5-FU cardiotoxicity. Thus, we investigated this effect and the involved mechanisms in 5-FU induced heart injury. Forty male rats of Wistar albino species were used and divided randomly into four groups. Group I is the control group, group II is EMP given group, group III is 5-FU cardiotoxic group and group IV is 5-FU plus EMP group. 5-FU (150 mg/kg) was administered as a single intraperitoneal (i.p.) dose on 1st day to induce cardiotoxicity with or without EMP (30 mg/kg/d) orally for 5 days. The dose of 5-FU is relevant to the human toxic dose. Our data showed that 5-FU given group caused cardiotoxicity with significant increase of serum cardiac enzymes, toll like receptors, enhancement of nuclear factor kappa B (NF-κB), interleukin1β (IL1β), IL6, myeloid-differentiation-factor 88 (MYD88), heart weight, malondialdehyde (MDA), tumor-necrosis-factor-alpha (TNFα), sodium glucose co-transporter 2 (SGLT2), P53 and caspase3 expression with clear histopathological features of cardiotoxicity. Moreover, there is a significant decrease in reduced glutathione (GSH) and total antioxidant capacity (TAC). Interestingly, co-administration of EMP could ameliorate 5-FU induced biochemical and histopathological changes. This effect may be due to modulation of SGLT2, decreasing inflammation, oxidative stress and apoptosis with downregulation of an essential inflammatory cascade that mediates 5-FU cardiotoxicity; TNFα/TLR/NF-κB.
{"title":"Molecular mechanism of empagliflozin cardioprotection in 5-fluorouracil (5-FU)-induced cardiotoxicity via modulation of SGLT2 and TNFα/TLR/NF-κB signaling pathway in rats","authors":"Marwa Monier Mahmoud Refaie, Sayed Shehata, Maram El-Hussieny, Michael Atef Fawzy, Nagwa Zenhom Mustafa Ahmed, Heba Marey, Asmaa Mohammed Hishmat, Turki Alkully, Eman Shaaban Mahmoud Abd El Rahman","doi":"10.1007/s43188-023-00204-1","DOIUrl":"https://doi.org/10.1007/s43188-023-00204-1","url":null,"abstract":"Abstract One of the commoly used chemotherapeutic agents is 5-Fluorouracil (5-FU). Unfortunately, the clinical administration of 5-FU is complicated with serious cardiotoxic effects and the safe use becomes an urgent task in cardio-oncology. Till now, there are no studies discussed the role of empagliflozin (EMP) against 5-FU cardiotoxicity. Thus, we investigated this effect and the involved mechanisms in 5-FU induced heart injury. Forty male rats of Wistar albino species were used and divided randomly into four groups. Group I is the control group, group II is EMP given group, group III is 5-FU cardiotoxic group and group IV is 5-FU plus EMP group. 5-FU (150 mg/kg) was administered as a single intraperitoneal (i.p.) dose on 1st day to induce cardiotoxicity with or without EMP (30 mg/kg/d) orally for 5 days. The dose of 5-FU is relevant to the human toxic dose. Our data showed that 5-FU given group caused cardiotoxicity with significant increase of serum cardiac enzymes, toll like receptors, enhancement of nuclear factor kappa B (NF-κB), interleukin1β (IL1β), IL6, myeloid-differentiation-factor 88 (MYD88), heart weight, malondialdehyde (MDA), tumor-necrosis-factor-alpha (TNFα), sodium glucose co-transporter 2 (SGLT2), P53 and caspase3 expression with clear histopathological features of cardiotoxicity. Moreover, there is a significant decrease in reduced glutathione (GSH) and total antioxidant capacity (TAC). Interestingly, co-administration of EMP could ameliorate 5-FU induced biochemical and histopathological changes. This effect may be due to modulation of SGLT2, decreasing inflammation, oxidative stress and apoptosis with downregulation of an essential inflammatory cascade that mediates 5-FU cardiotoxicity; TNFα/TLR/NF-κB.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"201 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135738937","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}
Pub Date : 2023-09-26DOI: 10.1007/s43188-023-00211-2
Min Seo Lee, Eun Jeong Park, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Hye Suk Lee
{"title":"Comparative metabolism of fargesin in human, dog, monkey, mouse, and rat hepatocytes","authors":"Min Seo Lee, Eun Jeong Park, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Hye Suk Lee","doi":"10.1007/s43188-023-00211-2","DOIUrl":"https://doi.org/10.1007/s43188-023-00211-2","url":null,"abstract":"","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134961084","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}
{"title":"Neurobehavioral effects of the exposure to mercury vapor and methylmercury during postnatal period on mice","authors":"Jin-Yong Lee, Minoru Yoshida, Masahiko Satoh, Chiho Watanabe","doi":"10.1007/s43188-023-00210-3","DOIUrl":"https://doi.org/10.1007/s43188-023-00210-3","url":null,"abstract":"","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136136071","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}
Pub Date : 2023-08-24eCollection Date: 2023-10-01DOI: 10.1007/s43188-023-00208-x
Yeonju Kwon, Hyein Lee, Hyemin Park, Boyoung Lee, Tae-Uk Kwon, Yeo-Jung Kwon, Young-Jin Chun
The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated β-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our findings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.
Hippo通路是一种通过调节细胞增殖和凋亡来控制动物器官大小的信号通路。Yes-associated protein 1（YAP1）是一种与癌症的发展和进展相关的癌基因，通过Hippo通路下调，并与癌症的发展和发展相关。叶皮样3（YPEL3）是肿瘤抑制蛋白p53的靶基因，其激活已被证明可以抑制细胞生长、诱导细胞衰老和抑制肿瘤细胞转移。在本研究中，我们发现YAP1抑制了乳腺癌症细胞中YPEL3的表达。此外，细胞衰老的标志蛋白层粘连蛋白B1的减少，加上衰老相关的β-半乳糖苷酶的激活，表明通过YAP1下调上调YPEL3水平可以诱导细胞衰老。此外，YPEL3水平的升高导致线粒体中较高水平的耗氧率，从而促进细胞凋亡。提示YPEL3在调节乳腺癌症细胞氧化应激和细胞凋亡中起着至关重要的作用。因此，YAP1和YPEL3之间的相互作用代表了一种由Hippo信号通路介导的细胞衰老的新机制。总之，我们的研究结果表明，Hippo信号通路在调节细胞衰老中发挥着重要作用，这可能对癌症等疾病新治疗策略的开发具有启示意义。
{"title":"YPEL3 expression induces cellular senescence via the Hippo signaling pathway in human breast cancer cells.","authors":"Yeonju Kwon, Hyein Lee, Hyemin Park, Boyoung Lee, Tae-Uk Kwon, Yeo-Jung Kwon, Young-Jin Chun","doi":"10.1007/s43188-023-00208-x","DOIUrl":"10.1007/s43188-023-00208-x","url":null,"abstract":"<p><p>The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated β-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our findings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 4","pages":"711-719"},"PeriodicalIF":1.6,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41178390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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