Toxicology Research最新文献

{"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}

{"title":"Asiatic acid improves the damage of HaCaT cells induced by nitrogen mustard through inhibiting endoplasmic reticulum stress.","authors":"Haoyin Liu, Jin Cheng, Feng Ye, Xunhu Dong, Wei Ge, Xiaogang Wang, Yuanpeng Zhao, Guorong Dan, Mingliang Chen, Yan Sai","doi":"10.1093/toxres/tfaf019","DOIUrl":"10.1093/toxres/tfaf019","url":null,"abstract":"<p><p>Nitrogen mustard (NM) belongs to vesicant agents. Blisters are one of the important characteristics of NM skin damage. It is urgent to further elucidate the mechanism and develop effective countermeasures for the skin damage induced by NM. The endoplasmic reticulum (ER) is an important intracellular organelle, playing an important role in maintaining cellular homeostasis. In this study, we explored the role of endoplasmic reticulum stress (ERS) and the protective effect of asiatic acid (AA) in the HaCaT cells induced by NM. It was found that the key regulatory proteins of ERS, such as glucose regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), inositol requiring enzyme 1 (IRE1), Phospho-IRE1 (pIRE1), and TNF receptor associated factor 2 (TRAF2) were increased respectively in HaCaT cells exposed to NM compared with those of the control group, showing an increasing trend with the increase of NM exposure concentration and exposure time. Additionally, the protein expression of Caspase-3 and the Cleaved-Caspase-3 was also increased by NM in HaCaT cells, resulting in the apoptosis of HaCaT cells. Meanwhile, the content of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was also increased in HaCaT cells exposed to NM. Further study showed that AA pretreatment could decrease the protein expression of GRP78, XBP1 and IRE1, pIRE1, TRAF2, Caspase-3, and Cleaved-Caspase-3. And moreover, AA also could reduce the content of TNF-α and IL-6. Overall, the present study showed that AA played an important protective effect in HaCaT cells exposed to NM through the inhibition of the ERS-induced apoptosis and inflammatory response.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf019"},"PeriodicalIF":2.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447378","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":"Chronic benzene exposure impairs the self-renewal capacity of HSPCs in C57BL/6 mice.","authors":"Yan Zhang, Jin Zhou, Jianxin Zhao, Xiurong Cheng, Caihong Xing","doi":"10.1093/toxres/tfaf021","DOIUrl":"10.1093/toxres/tfaf021","url":null,"abstract":"<p><p>In this study, we aimed to investigate the effects of chronic benzene exposure on the self-renewal capacity of C57BL/6 bone marrow HSPCs. Twenty-four male C57BL/6 mice were randomly divided into two groups: the control group and the benzene-exposed group. Mice in the benzene-exposed group inhaled 1,000 mg/m³ (308 ppm; conversion factor: 20 °C, 101 kPa, 1 ppm = 3.25 mg/m³) benzene for 32 weeks and the control group mice inhaled clean air. The peripheral blood hematological alterations were monitored every two weeks. Competitive bone marrow transplantation was performed to assess the self-renewal capacity of bone marrow HSPCs and the donor cell chimerism was quantified through flow cytometry. By the fourth week of benzene exposure, significant reductions in leukocytes, erythrocytes, and hemoglobin levels (<i>P</i> < 0.05) were observed, suggesting the development of benzene poisoning in mice. In the B6.SJL recipient mice, the chimerism ratio of bone marrow cells from C57BL/6 donors exposed to benzene for 20 weeks significantly decreased after transplantation (16 weeks post-transplant: 52.58% ± 17.38% in controls vs. 3.89% ± 1.96% in the benzene group, <i>P</i> < 0.05). Furthermore, the chimerism ratio in recipients of 32-week benzene-exposed donors approached zero by week 84 post-transplant, suggesting a loss of self-renewal capacity in bone marrow HSPCs due to benzene exposure. The study concludes that bone marrow suppression and the diminished self-renewal ability of C57BL/6 bone marrow HSPCs may lead to bone marrow failure in mice, contributing to the potential occurrence of MDS.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf021"},"PeriodicalIF":2.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447458","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":"Effect of Pimecrolimus on apoptotic pathways in H₂O₂-treated neuron like differentiated-SH-SY5Y cells: a molecular docking and mechanistic study.","authors":"Fatma Gonca Kocanci","doi":"10.1093/toxres/tfaf020","DOIUrl":"10.1093/toxres/tfaf020","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs), including Alzheimer's and Parkinson's, are marked by progressive neuronal loss, driven largely by oxidative stress and apoptosis. Developing neuroprotective strategies to counteract these processes is critical for managing such disorders. This study explores the neuroprotective effects of pimecrolimus, a calcineurin inhibitor, in mitigating hydrogen peroxide (H₂O₂)-induced cytotoxicity in neuron-like differentiated SH-SY5Y (d-SH-SY5Y) cells. The investigation focuses on apoptosis modulation, cell viability, and molecular docking interactions with apoptotic proteins. SH-SY5Y cells were differentiated with retinoic acid and treated with H₂O₂ (250 μM) alone or in combination with pimecrolimus (0.01, 0.1, and 1 μM) for 24 h. Cell viability was assessed using lactate dehydrogenase (LDH) assays. Additionally, malondialdehyde (MDA) levels were measured to assess oxidative stress in SH-SY5Y cells following the treatment conditions. Molecular docking analyses evaluated pimecrolimus' interactions with bax, bcl-2, caspase-3 and caspase-8 proteins, using Venetoclax as a positive control. Apoptosis-related protein levels were analyzed via ELISA, qRT-PCR, and immunofluorescence staining (cleaved caspase-3 and DAPI). Molecular docking showed strong binding of pimecrolimus to bax, bcl-2, caspase-3 and caspase-8, with comparable binding energies to Venetoclax. LDH and MDA assays demonstrated significant reductions in H₂O₂-induced cytotoxicity with pimecrolimus. ELISA and qRT-PCR revealed that H₂O₂ increased pro-apoptotic bax, caspase-3 and caspase-8 levels while decreasing anti-apoptotic bcl-2 levels. Pimecrolimus co-treatment reversed these effects in a dose-dependent manner. Immunofluorescence confirmed reduced apoptosis and cell death with pimecrolimus. Pimecrolimus effectively mitigates oxidative stress and apoptosis in H₂O₂-treated d-SH-SY5Y cells. These findings suggest its potential as a neuroprotective agent for managing (NDs).</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf020"},"PeriodicalIF":2.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447483","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}