Toxicology Research最新文献

{"title":"Meta-analysis of studies testing the association between air pollution and live birth rates in women undergoing assisted reproductive technology.","authors":"Juan Hu, Huiqiu Zheng, Yan Wu, Qing Yan, Minghao Zhang, Shikun Sun, Meidi Gong, Rao Zheng, Shujing Jia, Rui Zhou, Jing Wu","doi":"10.1093/toxres/tfaf028","DOIUrl":"10.1093/toxres/tfaf028","url":null,"abstract":"<p><p>Amidst a proliferation of research on air pollutants and negative pregnancy outcomes, uncertainty lingers regarding their impact on live birth rates in women receiving assisted reproductive technology (ART). This meta-analysis aims to clarify this vital issue. We searched EMBASE, PubMed, and Web of Science databases, targeting articles published prior to 2023 August 2. We pooled relative risks (RRs) and their corresponding 95% confidence intervals (95%CIs) across all included studies to assess the relationship between exposure to air pollutants and live birth rates. From an initial 5,785 citations, we identified five eligible papers with a total sample size of approximately 282,000 participants. In the year prior to oocyte retrieval, for every 10 μg/m³ increase in fine particulate matter (PM_2.5) (RR: 0.94, 95%CI: 0.92-0.97) and coarse particulate matter (PM₁₀) (RR: 0.95, 95%CI: 0.92-0.97), the probability of live birth decreased by 6% and 5%, respectively. For every additional ppb increase in nitrogen dioxide (NO₂) (RR: 0.92, 95%CI: 0.87-0.98), the likelihood of live birth decreased by 8%. This meta-analysis demonstrates adverse associations between air pollution and live birth rates in women undergoing ART. These findings highlight further elucidate the observed associations, as well as to explore potential mechanisms and implications for reproductive health.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf028"},"PeriodicalIF":2.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565497","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":"Comparative in vitro and in silico evaluation of the toxic effects of metformin and/or ascorbic acid, new treatment options in the treatment of Melasma.","authors":"Hülya Tezel Yalçın, Deniz Arca Çakır, Anıl Yirün, Sonia Sanajou, Gözde Işık, Özlem Bozdemir, İbrahim Özçelik, Merve Güdül Bacanlı, Naciye Dilara Zeybek, Terken Baydar, Pınar Erkekoğlu","doi":"10.1093/toxres/tfaf025","DOIUrl":"10.1093/toxres/tfaf025","url":null,"abstract":"<p><p>Melasma is a chronic condition that leads to the buildup of melanin pigment in the epidermis and dermis due to active melanocytes. Even though it is considered a non-life-threatening condition, pigment disorders have a negative impact on quality of life. Since melasma treatment is not sufficient and complicated, new treatment options are sought. Research on metformin and ascorbic acid suggested that they might be used against melasma in the scope of \"drug repositioning.\"The MNT-1 human melanoma cell line was used to assess the effects of metformin, ascorbic acid, and metformin+ascorbic acid combination on cytotoxicity and oxidative stress. Melanin, cAMP, L-3,4-dihydroxyphenylalanine (L-DOPA) and tyrosinase levels were determined by commercial ELISA kits and tyrosinase gene expression was analyzed with RT-qPCR. Cytopathological evaluations were performed by phase contrast microscopy. Tyrosinase expression was determined by immunofluorescence (IF) staining of MNT-1 cells. The online service TargetNet was used for biological target screening. The parameters were not significantly altered by ascorbic acid applied at non-cytotoxic concentrations. On the contrary, metformin dramatically raised tyrosinase and intracellular ROS levels. Moreover, intracellular ROS levels and tyrosinase levels were found to be considerably elevated with the combined treatment. Also, potential metformin and ascorbic acid interactions were determined. According to the results, it can be said that these parameters were not significantly altered by ascorbic acid. On the contrary, metformin dramatically raised tyrosinase and intracellular oxidative stress levels. Moreover, intracellular oxidative stress and tyrosinase levels were elevated with the combined treatment. In conclusion, individual treatments of ascorbic acid or metformin may only provide a limited effect when treating melasma and extensive in vitro and in vivo research are required.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf025"},"PeriodicalIF":2.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555325","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 of imatinib mesylate and a related impurity: in vitro and in vivo approaches.","authors":"Cássia Franciele Rosa da Silva Rocha, Bruna Saraiva Hermmann, Juliana Machado Kayser, Gabriela Zimmermann Prado Rodrigues, Günther Gehlen, Fernanda Brião Menezes Boaretto, Jaqueline Nascimento Picada, Juliane Deise Fleck, Mariele Feiffer Charão, Simone Gasparin Verza","doi":"10.1093/toxres/tfaf029","DOIUrl":"10.1093/toxres/tfaf029","url":null,"abstract":"<p><p>Imatinib mesylate (IM) is a widely used anticancer drug, mainly for treating chronic myeloid leukemia. However, pharmaceutical formulations may contain impurities, which in some cases can be more toxic than the parent compounds. This study aimed to compare the toxicity of IM and one of its impurities (IMP), N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine, using progressively complex models. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium, neutral red uptake and sulforhodamine B colorimetric assays. Mutagenic activity was assessed using the Ames test<i>.</i> In vivo assays were performed using both the invertebrate <i>C. elegans</i> and vertebrate zebrafish embryo models. In Vero cell cultures, the cytotoxicity of IM and IMP was found to be similar across the colorimetric assays tested. Neither IM nor IMP showed mutagenic effects in the Ames test. In the <i>C. elegans</i> lethality and development assay the toxicity profiles of the compounds were similar. However, in the Fish Embryo Acute Toxicity assay, the LC₅₀ value for IMP (0.735 μg/mL) was significantly lower than that for IM (60.86 μg/mL), indicating greater toxicity for IMP. Furthermore, sublethal effects such as yolk-sac edema, pericardial edema, and tail deformities, were observed in embryos treated with IMP, even at low concentrations, indicating potential hazards associated with IMP. This study is the first to evaluate the toxicity of an IM subproduct, previously reported in pharmaceutical formulations, using different models. The Zebrafish model demonstrated higher sensitivity in predicting the toxic response of the TKI subproduct.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf029"},"PeriodicalIF":2.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565503","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":"The effect and mechanism of atorvastatin regulating PI3K-Akt-mTOR pathway on radiosensitivity of hepatocellular carcinoma cells.","authors":"Zhengzheng Deng, Jinjing Guo, Zihao Zhu, Qiancheng Qing, Dangting Wan, Pengyuan Lei, Qi Liu, Bo Huang","doi":"10.1093/toxres/tfae202","DOIUrl":"10.1093/toxres/tfae202","url":null,"abstract":"<p><p>Radiation therapy is an important method to treat liver cancer, but because of the strong DNA repair ability of liver cancer cells, even after receiving high doses of radiation still can not get satisfactory results. Atorvastatin (ATO) is a lipophilic and tissue-selective inhibitor of HMG-CoA reductase whose anticancer effects have been validated in various cells, but its effect on the radiation sensitivity of hepatocellular carcinoma cells remains unclear. Therefore, Therefore, this study explored the radiosensitivity of ATO and its possible mechanism by pretreating HepG2 with ATO and collecting HepG2 cells after irradiation. It was found that atorvastatin can not only affect the survival of liver cancer cells when used alone, but also enhance the radiation sensitivity of HepG2 cells. The study found that ATO significantly exacerbated the inhibitory effects of IR on the growth, proliferation, and migration of HepG2 cells. Measurement of ROS, SOD, GPx, and MDA levels indicated that ATO enhanced IR-induced oxidative stress, further promoted the decrease of Mitochondrial Membrane Potential, increased the rate of apoptosis in HepG2, upregulating pro-apoptotic proteins Bax and Cleaved-Caspase 3, and downregulating anti-apoptotic proteins Bcl-2. Western blot analysis showed that the PI3K-Akt-mTOR pathway was inhibited, leading to the activation of cytotoxic autophagy in HepG2 and an increase in the expression of the LC-3II protein. In summary, ATO, in combination with IR, enhances the oxidative stress response of HepG2 induced by IR, promotes autophagy by inhibiting the PI3K-Akt-mTOR pathway, and thereby potentially enhances the radiosensitivity of HepG2 as a pharmacological intervention.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae202"},"PeriodicalIF":2.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514290","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":"Editorial.","authors":"Shirley Price","doi":"10.1093/toxres/tfaf018","DOIUrl":"https://doi.org/10.1093/toxres/tfaf018","url":null,"abstract":"","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf018"},"PeriodicalIF":2.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497730","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":"Acute anxiogenic effect of lisdexamphetamine dimesylate in zebrafish: implications of off-label cognitive enhancement use.","authors":"Nicole Berton, Luciane Dellazari da Silva do Prado, Jessica Nardi, Inara Carbonera Biazus, Laíse Mattiollo, Karen Julia de Souza Dos Santos, Nicoli da Rosa Amaral, Lisiane Siqueira, Amanda Carolina Cole Varela, Gabriéla Witkowski Rutikoski, Leonardo José Gil Barcellos, Luciana Grazziotin Rossato-Grando","doi":"10.1093/toxres/tfaf027","DOIUrl":"10.1093/toxres/tfaf027","url":null,"abstract":"<p><p>The off-label use of lisdexamphetamine dimesylate (LDX), a prodrug of dextroamphetamine, for cognitive enhancement has raised concerns due to its potential risk effects in neurotypical individuals. This study investigates the acute toxic effects of LDX exposure in zebrafish (<i>Danio rerio</i>), used here as a translational model. Zebrafish were exposed to 70, 100, and 140 mg/L^-1 of LDX to assess changes in anxiety-related, social-related and exploratory behaviors and cognitive function through novel tank test, social preference test, spatial memory test, and light-dark test, respectively. We also evaluated the occurrence of lipid peroxidation and changes in the total protein content after LDX treatments. Our findings reveal that acute LDX exposure significantly increases anxiety-like behaviors, as evidenced by increased bottom-dwelling and decreased top-dwelling times in novel tank tests, without enhancing cognitive function. The concentrations also cause increases in lipid peroxidation and total protein content, making this finding likely to be directed at the fish's inflammatory response. Our results highlight that acute use of LDX does not improve cognition, but causes an anxiogenic effect, and showed oxidative damage by increasing total proteins, highlighting potential health risks associated with non-medical use of LDX, particularly among neurotypical individuals seeking cognitive benefits.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf027"},"PeriodicalIF":2.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490186","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":"An overview on Sjögren's syndrome and systemic lupus erythematosus' genetics.","authors":"Ilker Ates, Ulku Terzi, Sinan Suzen, Lalu Muhammad Irham","doi":"10.1093/toxres/tfae194","DOIUrl":"10.1093/toxres/tfae194","url":null,"abstract":"<p><p>Major autoimmune rheumatic disorders, such as systemic lupus erythematosus and Sjögren's syndrome, are defined by the presence of autoantibodies. These diseases are brought on by immune system dysregulation, which can present clinically in a wide range of ways. The etiologies of these illnesses are complex and heavily impacted by a variety of genetic and environmental variables. The most powerful susceptibility element for each of these disorders is still the human leukocyte antigen (HLA) area, that was the initial locus found to be associated. This region is primarily responsible for the HLA class II genes, such as DQA1, DQB1, and DRB1, however class I genes have also been linked. Numerous genetic variants that do not pose a risk to HLA have been found as a result of intensive research into the genetic component of these diseases conducted over the last 20 years. Furthermore, it is generally acknowledged that autoimmune rheumatic illnesses have similar genetic backgrounds and share molecular pathways of disease, including the interferon (IFN) type I routes. Pleiotropic sites for autoimmune rheumatic illnesses comprise TNIP1, DNASEL13, IRF5, the HLA region, and others. It remains a challenge to determine the causative biological mechanisms beneath the genetic connections. Nonetheless, functional analyses of the loci and mouse models have produced recent advancements. With an emphasis on the HLA region, we present an updated summary of the structure of genes underpinning both of these autoimmune rheumatic illnesses here.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae194"},"PeriodicalIF":2.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481732","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":"Correction to: Exploring the potential of selenium nanoparticles and fabricated selenium nanoparticles @vitamin C nanocomposite in mitigating nicotine-induced testicular toxicity in rats.","authors":"","doi":"10.1093/toxres/tfaf026","DOIUrl":"https://doi.org/10.1093/toxres/tfaf026","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/toxres/tfae154.].</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf026"},"PeriodicalIF":2.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481737","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":"Correction to: Sterile inflammation induced by respirable micro and nano polystyrene particles in the pathogenesis of pulmonary diseases.","authors":"","doi":"10.1093/toxres/tfaf022","DOIUrl":"https://doi.org/10.1093/toxres/tfaf022","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/toxres/tfae138.].</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf022"},"PeriodicalIF":2.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447482","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":"Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells.","authors":"Farzaneh Motafeghi, Maryam S Fakhri B, Nasrin Ghassemi Barghi","doi":"10.1093/toxres/tfaf023","DOIUrl":"10.1093/toxres/tfaf023","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Erythropoietin (EPO) is known for its role in hematopoiesis and also exhibits anti-inflammatory, anti-apoptotic, antioxidant, and cytoprotective properties. However, its clinical application is limited by hematopoietic side effects. ARA290, a non-hematopoietic derivative of EPO, selectively activates the innate repair receptor (IRR) and replicates these protective effects without the associated hematopoietic complications. Cadmium (Cd), a prevalent environmental toxin, causes neurotoxic damage through mechanisms such as oxidative stress, genotoxicity, apoptosis, and inflammation. This study explored ARA290's neuroprotective effects against cadmium-induced toxicity in PC12 cells, an in vitro model for neuronal health. PC12 cells pretreated with ARA290 showed significantly improved cell viability in the MTT assay, indicating reduced cytotoxicity. The comet assay revealed decreased DNA damage, suggesting reduced genotoxicity. ARA290 also alleviated oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside increased glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activities. A marker of apoptosis, TUNEL-positive cells, was significantly reduced. Additionally, ARA290 decreased inflammatory markers such as TNF alpha, IL1ß and IL 6. These findings demonstrate that ARA290, via IRR activation, provides robust neuroprotection against cadmium-induced toxicity, suggesting a multi-faceted protective mechanism. This highlights ARA290's potential therapeutic role in managing heavy metal-induced neurotoxicity and supports further research into its long-term effects and applications in other neurodegenerative diseases or conditions involving environmental toxins.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Highlights: &lt;/strong&gt;ARA290 as a Neuroprotective Agent: ARA290, a modified form of erythropoietin that doesn't affect blood production, shows promising neuroprotective effects. It helps counteract the harmful effects of cadmium exposure on nerve cells by reducing oxidative stress, inflammation, cell death, and DNA damage.Reducing Oxidative Stress: ARA290 plays a key role in lowering oxidative stress by cutting down on harmful molecules like reactive oxygen species (ROS) and malondialdehyde (MDA). At the same time, it boosts the body's natural antioxidant defenses, including glutathione (GSH), superoxide dismutase (SOD), and overall antioxidant capacity.Protecting DNA Integrity: By reducing DNA damage caused by cadmium, ARA290 helps preserve the genetic stability of nerve cells. This protective effect is evident in laboratory tests, where it lowers the extent of DNA damage seen in the comet assay.Fighting Inflammation and Cell Death: ARA290 also has strong anti-inflammatory and anti-apoptotic effects. It reduces levels of inflammation markers like TNF-α, IL-1β, and IL-6, and significantly cuts down on nerve cell death, as seen in fewer TUNEL-positive cells in experiments.A Therapeutic Promi","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf023"},"PeriodicalIF":2.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447484","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}