Toxicological Research最新文献

{"title":"Regulatory frameworks for fragrance safety in cosmetics: a global overview.","authors":"Priyanka Rana, Diksha Pathania, Prakriti Gaur, Sunil Kumar Patel, Medha Bajpai, Neera Tewari Singh, Ruchi Pandey, Shakti Vinay Shukla, Aditya Bhushan Pant, Ratan Singh Ray, Ashish Dwivedi","doi":"10.1007/s43188-025-00283-2","DOIUrl":"https://doi.org/10.1007/s43188-025-00283-2","url":null,"abstract":"<p><p>Fragrances play a crucial role in cosmetic products, influencing consumer preferences and enriching sensory experiences. However, making sure these products are safe, especially concerning natural and synthetic fragrances, requires robust regulatory frameworks. This review offers a global perspective on the regulatory systems governing the safety of fragrances. It begins by examining the fundamental differences between natural and synthetic fragrances, highlighting their origins and unique safety considerations. Natural fragrances, sourced from botanicals like essential oils, have a long history of human exposure. Synthetic fragrances, on the other hand, are artificially manufactured compounds that often lack sufficient safety data, thereby requiring strict regulation. Various countries have developed safety guidelines to address concerns such as skin sensitization, allergies, and health risks associated with fragrance use. This article provides a comprehensive analysis of these global regulatory frameworks, emphasizing both commonalities and disparities in safety standards for natural and synthetic fragrances. It also discusses ongoing efforts to harmonize regulations and improve fragrance safety in cosmetics. By offering this in-depth overview of regulatory approaches, the article serves as a valuable resource for cosmetics industry professionals. It provides insights into the evolving landscape of cosmetics regulations worldwide, aiding stakeholders in navigating the complexities of natural and synthetic fragrance safety and ultimately safeguarding consumer well-being.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"199-220"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038164","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}

{"title":"Short-term health effects of tear agents chlorobenzylidenemalononitrile and oleoresin capsicum during the civil riots of Santiago de Chile in 2019-2020.","authors":"Carlos Jara Bravo, José Antonio Cernuda Martínez, Pedro Arcos González","doi":"10.1007/s43188-025-00282-3","DOIUrl":"https://doi.org/10.1007/s43188-025-00282-3","url":null,"abstract":"<p><p>Chlorobenzylidenemalononitrile (CS) and Oleoresin Capsicum (OC) were tear gasses used as anti-riot control agents during social unrest riots in Chile (October 2019-March 2020). This study posed as a research question what were the short-term health effects of CS and OC and their patterns of temporal occurrence in a sample of inhabitants and health care volunteer brigades of the Plaza Italia (city of Santiago, Chile) during the riots. A retrospective cross-sectional study was conducted in 112 exposed people (inhabitants and health care volunteers) affected by CS and OC. 62 harmful effects were studied classified in three time periods of occurrence: immediate effects (between exposure and one hour), secondary effects (from one hour after exposure and up to 24 h), and subsequent effects (days after exposure). The use of CS and OC in Santiago riots 2019-2020 produced harmful effects on both groups: inhabitants and brigade health care volunteers. The frequency of effects was, from most to least common: 62.5% eye pain or burning, 56.2% throat irritation, 54.4% respiratory distress, 52.6% skin pain or burning, 51.7% impaired vision, 37.5% skin erythema, 31.2% headache, 31.2% irregular breathing, 25.8% conjunctival injection, 29.4% nausea, 27.6% disorientation, 26.7 high blood pressure, 25.8% lip pain, 24.1% rhinitis, 24.1% skin sensitivity, 22.3% diarrhea, 20.5% contact dermatitis, 18.7% conjunctivitis, 16.9% skin vesicles, 16% tachycardia, 14.4 cough with phlegm and 9.8% corneal abrasion. 22 effects were more frequent (<i>p</i> < 0.05) in health care volunteers than among residents. High blood pressure was more frequent (<i>p</i> < 0.05) among residents. Immediate most frequent effects were pain or burning, impaired vision, respiratory difficulty, irregular breathing, skin pain and burning, skin erythema, nausea, tachycardia, and hypertension. Secondary effects were diarrhea, skin vesicles, and eye pain or burning. Subsequent most frequent effects among healthcare personnel were conjunctivitis, skin pain, burning, rhinitis, and diarrhea. Among residents, the most common effects were skin pain, burning, and impaired vision.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"291-301"},"PeriodicalIF":1.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027647","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}

{"title":"Toxicity of diclofenac sodium salt after two weeks of daily intramuscular administration in cynomolgus monkeys.","authors":"Sieun Yoo, Jung-Ho Noh, Hong-Soo Lee, Sang-Hee Lee, Eunji Choi, Dong-Il Kim, Seung Eui Min, Kang-Hyun Han, Sang Kyum Kim","doi":"10.1007/s43188-025-00281-4","DOIUrl":"https://doi.org/10.1007/s43188-025-00281-4","url":null,"abstract":"<p><p>Diclofenac sodium salt (DSS) has been extensively studied in pharmacological research to better understand its pain relief and inflammation-reducing properties. However, it is crucial to evaluate the safety profile of this non-steroidal anti-inflammatory drug, particularly in nonhuman primates (NHPs), such as cynomolgus monkeys. Understanding the potential adverse effects and toxicity of DSS in NHP is critical for determining their overall safety and use in clinical settings. Further investigation into its toxicity to NHPs would provide valuable information for developing and using this drug in medical practice. Our aim was to evaluate the toxicity of DSS administered repeatedly to cynomolgus monkeys to identify its safety profile in NHPs. The general toxicity of DSS was established using a 2-week repeated-dose toxicity test. Twenty-four cynomolgus monkeys were intramuscularly injected with 0, 0.33, 1, and 3 mg/kg of DSS each day. This study assessed the potential adverse effects and toxicity of DSS in these monkeys, providing valuable data for understanding its safety in clinical settings. The 2-week repeated-dose toxicity study of DSS revealed no treatment-related changes in body weight, food consumption, ophthalmology, or general symptoms. Furthermore, no significant changes were observed in hematological, clinical chemistry, or urinalysis data. Histopathological examination revealed decreased cellularity (lymphocytes) in both the thymus and spleen (white pulp). The sternal bone marrow had a higher cell count than usual. Furthermore, mixed cell and mononuclear cell infiltration, inflammation, myofiber degeneration, and muscle fiber necrosis were observed at the injection site (skin), but these findings were not considered adverse effects. Notably, the no observed adverse effect level of DSS was estimated to be greater than 3 mg/kg in both males and females. Therefore, this study established a non-toxic dose of DSS, laying the groundwork for further nonclinical studies to assess the safety of DSS using NHP.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-025-00281-4.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"279-290"},"PeriodicalIF":1.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052820","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}

{"title":"Targeting IDH1 mutation-driven Nrf2 signaling to suppress malignant behavior in fibrosarcoma cells.","authors":"Seoyeon Park, Kyung-Soo Chun, Do-Hee Kim","doi":"10.1007/s43188-025-00284-1","DOIUrl":"https://doi.org/10.1007/s43188-025-00284-1","url":null,"abstract":"<p><p>Isocitrate dehydrogenase 1 (IDH1) mutations are prevalent in various cancers and have significant implications for tumor biology. It is known that cancer cells with IDH1 mutations, particularly R132C or R132H, exhibit decreased production of nicotinamide adenine dinucleotide phosphate and thus impaired glutathione synthesis. This study investigated the roles of IDH1 mutations in the regulation of nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated signaling pathways in fibrosarcoma HT1080 cells harboring the IDH1 R132C mutation. Knockdown of IDH1 using siRNA in HT1080 cells inhibited Nrf2 stabilization and reduced the expression of antioxidant genes, thereby providing favorable conditions for cancer progression. In addition, inhibition of IDH1 decreased reactive oxygen species (ROS) production and impaired cell migration, highlighting its role in promoting malignant behavior such as colony-forming ability. Small molecule inhibitors targeting the IDH1 R132 mutation suppressed cell migration and colony formation in HT1080 cells. Moreover, we observed that IDH and Nrf2 contribute to immune evasion by modulating the expression of programmed death-ligand 1 (PD-L1) in HT1080 cells. Altogether, our findings provide valuable insights for the development of therapeutic approaches for IDH1-mutant cancers. We suggest targeting the IDH1-Nrf2 axis as a strategy to regulate the immune response and inhibit cell migration in fibrosarcoma.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-025-00284-1.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"267-278"},"PeriodicalIF":1.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033643","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}

{"title":"<i>Sargassum horneri</i> extract attenuates high-dose acetaminophen-induced hepatotoxicity by enhancing the antioxidant activity and inhibiting acetaminophen activation in the mouse liver.","authors":"Jiwon Hwang, Hyo Jin Kim, Yubin Song, Young-Ok Son, Youngheun Jee, Hyun Jung Kim, Jin-Hyeon Kim, Young-Suk Jung, Doyoung Kwon","doi":"10.1007/s43188-025-00278-z","DOIUrl":"https://doi.org/10.1007/s43188-025-00278-z","url":null,"abstract":"<p><p><i>Sargassum horneri</i> is an edible brown seaweed used as traditional medicine in various East Asian countries, such as China and Korea. Its therapeutic effects, including antioxidant and anti-inflammatory activities, have been reported in animal models of respiratory diseases and allergic disorders. However, its specific effects on liver health remain ambiguous. Therefore, in this study, we aimed to examine the effects of <i>S. horneri</i> extract (SHE) on acetaminophen (APAP)-induced hepatotoxicity, a common clinical cause of drug-induced liver injury. SHE-pretreated male mice were injected with a high dose of APAP. SHE alleviated APAP-induced liver injury and inhibited lipid peroxidation and glutathione (GSH) depletion. It also enhanced the hepatic total antioxidant capacity in APAP-treated mice, exhibiting direct radical scavenging activity against APAP-induced oxidative stress. Levels of the hepatic antioxidant enzymes, superoxide dismutase-1/2 and GSH peroxidase 1, were unaffected by SHE; however, catalase levels decreased by APAP were restored by the extract. Protein levels of the APAP-metabolizing enzymes, uridine 5'-diphospho-glucuronosyltransferase 1a6, sulfotransferase 1a1, GSH S-transferase a1, cytochrome P450 (Cyp)-1a2, Cyp2e1, and Cyp3a, were unaffected; however, Cyp1a activity was reduced by SHE. Plasma concentrations of APAP-GSH and APAP-cysteine conjugates were reduced by SHE in APAP-treated mice, indicating that SHE alleviates APAP hepatotoxicity by inhibiting Cyp1a-mediated metabolic activation of APAP. In conclusion, our results suggest that the increase in cellular antioxidant capacity and inhibition of APAP bioactivation are possible mechanisms underlying the hepatoprotective effects of SHE against high-dose APAP-induced acute liver injury.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"255-265"},"PeriodicalIF":1.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988178","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}

{"title":"Toxicity assessment using neural organoids: innovative approaches and challenges.","authors":"Si-Hyung Park, Woong Sun","doi":"10.1007/s43188-025-00279-y","DOIUrl":"10.1007/s43188-025-00279-y","url":null,"abstract":"<p><p>Assessment of toxicity and efficacy in the nervous system is essential to ensure the safety of compounds and the efficacy of neurotherapeutics. Recently, technologies using neural organoids to mimic the structural and functional properties of human brain tissue have been developed to improve our understanding of human-specific brain development and to model neurodevelopmental disorders. This approach offers the potential for standardized toxicity testing and large-scale drug screening at the organ level. Here, we review recent advances in neural organoids and explore the possibility of establishing more accurate and efficient systems for toxicological screening applications. Our review provides insights into toxicity and efficacy assessment research using neural organoids.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"91-103"},"PeriodicalIF":1.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516889","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}

{"title":"Picolinic acid, a tryptophan metabolite, triggers cellular senescence by targeting NOS/p38 MAPK/CK1α/MLKL signaling and metabolic exhaustion in red blood cells.","authors":"Sumiah A Alghareeb, Jawaher Alsughayyir, Mohammad A Alfhili","doi":"10.1007/s43188-025-00280-5","DOIUrl":"https://doi.org/10.1007/s43188-025-00280-5","url":null,"abstract":"<p><p>Anemia is among the most commonly reported adverse events of anticancer therapy. Picolinic acid (PA), an endogenous metabolite of tryptophan degradation in the kynurenine pathway, is a metal chelator with an anticancer activity. The objective of the current study is to investigate the modulation of red blood cell (RBC) lifespan by PA. Hemolytic and eryptotic markers were evaluated in the presence and absence of PA by photometric and flow cytometric methods. PA demonstrated a dual effect on hemolysis in which it was pro-hemolytic in isotonic media but anti-hemolytic under hypotonic challenge. PA also induced RBC senescence with reduced AChE activity. In addition, treated cells tested positive for annexin-V and Fluo4 and had a significantly lower forward scatter signal. Notably, ATP-replenished cells showed significantly enhanced chemoresistance against PA toxicity, which was also alleviated by ascorbic acid, L-NAME, SB203580, D4476, and necrosulfonamide. Furthermore, an inhibitory effect on PA was observed in incubation media supplemented with isosmotic sucrose but not urea. These data suggest that PA accelerates RBC aging through anticholinesterase activity and exhibits hemolytic and eryptotic properties characterized by phosphatidylserine externalization, Ca²⁺ mobilization, cell shrinkage, metabolic shutdown, and stimulation of the NOS/p38 MAPK/CK1α/MLKL pathway.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-025-00280-5.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 3","pages":"245-253"},"PeriodicalIF":1.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035821","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}

{"title":"Alleviating doxorubicin-induced reproductive toxicity: protective and androgenic effects of drone larvae on sperm morphology and hormonal balance.","authors":"Kağan Ağan, Salih Tunç Kaya, Aydan Fülden Ağan, Pınar Ağyar-Yoldaş, Taner Yoldaş, Ayşe İkinci-Keleş, Tuğçe Çaprazlı, Elif Arıca, Meral Kekeçoglu","doi":"10.1007/s43188-024-00270-z","DOIUrl":"10.1007/s43188-024-00270-z","url":null,"abstract":"<p><p>Male infertility and compromised sperm quality are common side effects of Doxorubicin (DOX), a widely used chemotherapy drug. Its detrimental impact on male reproductive cells underscores the urgent need for effective protective measures. Lyophilized drone larvae (DL) from apitherapy have emerged as a potential solution due to their reported protective properties. By exploring DL's therapeutic potential, this research seeks to address the pressing need for strategies to protect male reproductive health during cancer treatment. The study aims to evaluate the protective effects of lyophilized DL from apitherapy against DOX-induced testicular damage in adult <i>Sprague-Dawley</i> rats. DOX negatively impacts male reproductive cells, leading to infertility and compromised sperm quality. Investigating DL's protective properties is crucial for understanding its therapeutic potential in mitigating such adverse effects. Forty rats were divided into four groups: control, DOX-treated, DL-treated, and DOX + DL-treated. Histopathological assessments, biochemical analyses (TAS, TOS, CAT, SOD, GPX), inflammatory marker measurements (TNF-α, IL-1β, IL-6), and comet assays for DNA damage were conducted on testicular tissue and blood samples. DOX induced histopathological alterations in the testis and epididymis, which DL mitigated. DL increased TAS levels, counteracted DOX-induced decreases in glutathione peroxidase (GPx), total protein, albumin, and increases in total cholesterol. DL also mitigated the rise in Follicle-Stimulating Hormone (FSH) levels caused by DOX, while increasing testosterone levels and lowering Luteinizing Hormone (LH) levels. Inflammatory markers remained unaffected. Tail moment measurements indicated a protective effect against DOX-induced DNA damage in erythrocytes with DL. DL protected sperm morphology, count, and Johnsen's score from DOX-induced reductions, suggesting its potential in mitigating cancer treatment side effects on male reproductive health. The findings suggest that DL, as an apitherapy product, holds significant promise in mitigating DOX's adverse effects on male reproductive systems. However, further investigations into its mechanisms and clinical applications in cancer therapy are warranted, emphasizing the need for continued research to fully understand DL's therapeutic benefits.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"149-165"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516874","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}

{"title":"Exploring the safety parameters of <i>Athenaea velutina</i> ethanolic extract: a step towards harnessing its medicinal potential.","authors":"Jordana Luizi Dos Prazeres, Alisson Andrade Almeida, Renner Philipe Rodrigues Carvalho, Luiz Carlos Maia Ladeira, Luiz Pedro de Souza Costa, Markus Kohlhoff, Leandro Licursi de Oliveira, Mariana Machado-Neves, João Paulo Viana Leite","doi":"10.1007/s43188-024-00276-7","DOIUrl":"10.1007/s43188-024-00276-7","url":null,"abstract":"<p><p><i>Athenaea velutina</i> (Sendtn.) D'Arcy, a native plant of the Brazilian Atlantic Forest, has exhibited potential pharmacological effects due to the presence of withanolides with anti-cancer and anti-inflammatory activities. However, there is a lack of research on the safety and toxicity of this plant species. This study aimed to assess the safety of the ethanolic extract of <i>A. velutina</i> leaves (Av-E) through toxicity and phytochemical analysis. Acute [1000 mg kg^-1 body weight (BW)] and subacute (250, 500, and 1000 mg kg^-1 BW) toxicity tests were conducted on female Wistar rats, along with an evaluation of the toxic reversal effect. HPLC-HRMS revealed the presence of withanolide steroids in Av-E. Reduced alanine aminotransferase (ALT), bilirubin levels, and increased calcium concentrations were observed after the acute toxicity test. Subacute toxicity demonstrated lowered ALT (250 and 1000 mg kg^-1 BW) and aspartate aminotransferase (AST) (250 and 500 mg kg^-1 BW) levels and increased sodium concentration (250 mg kg^-1 BW). No fatalities or clinical signs of toxicity occurred, and histological and biochemical analysis revealed no apparent liver or kidney toxicity. In conclusion, Av-E exhibited no toxicity in the experiments, encouraging further research to develop new herbal medicines.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"175-188"},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516879","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}

{"title":"SRXN1 is a novel protective factor against methylmercury-induced apoptosis in C17.2 mouse neural stem cells.","authors":"Naoya Yamashita, Yukie Yokoyama, Ayano Kumagai, Ryoko Fukushima, Ryota Yamagata, Gi-Wook Hwang","doi":"10.1007/s43188-024-00277-6","DOIUrl":"10.1007/s43188-024-00277-6","url":null,"abstract":"<p><p>Methylmercury is an environmental pollutant that exhibits severe cerebral neurotoxicity and remains a worldwide problem. Motor and mental development disorders have been observed in children born to women who consumed relatively large amounts of methylmercury via contaminated fish during pregnancy. We previously found by RNA-sequencing analysis that treatment of C17.2 mouse neural stem cells with methylmercury induced the expression of SRXN1 (sulfiredoxin-1), a redox regulator. In this study, we examined the effect of methylmercury on SRXN1 expression and the role of SRXN1 in methylmercury-induced cell death. After C17.2 cells were treated with methylmercury, both mRNA and protein expression of SRXN1 increased in a time- and concentration-dependent manner. Because the induction of SRXN1 expression by methylmercury was suppressed by pretreatment with a transcription inhibitor, we searched the upstream region of the SRXN1 gene and found a binding sequence for transcription factor 3 (TCF3). Interestingly, the induction of SRXN1 expression by methylmercury was attenuated in cells in which TCF3 expression was suppressed by siRNA compared with control cells. This suggests that TCF3 is involved in the induction of SRXN1 expression by methylmercury. We previously reported that TCF3 overexpression suppressed methylmercury-induced apoptosis; in the present study, we found that SRXN1 overexpression also suppressed methylmercury-induced apoptosis, as assessed by cleaved caspase-3 expression. In summary, our results indicate that SRXN1 induced by TCF3-mediated expression is a novel protective factor against methylmercury-induced apoptosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-024-00277-6.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"41 2","pages":"167-173"},"PeriodicalIF":1.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516887","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}