{"title":"The Possible effect of Bosentan on the methotrexate-induced salivary gland changes in male rats: histological and Immunohistochemical study.","authors":"Rana Khairi Attarbashee, Heba Faiz Hamodat, Jawnaa Khalid Mammdoh, Hayder Ridha-Salman","doi":"10.1093/toxres/tfaf007","DOIUrl":"10.1093/toxres/tfaf007","url":null,"abstract":"<p><p>Methotrexate (MTX) is an antimetabolite drug utilized for managing a variety of cancers and autoinflammatory conditions. MTX may trigger detrimental effects in mout, h tissues, including salivary gland impairment. Bosentan (BOS), a drug that blocks endothelin receptors, has strengthened antioxidant, anti-inflammatory, and anti-apoptotic properties. The study aimed to estimate the protective effect of BOS on MTX-exacerbated salivary changes in Wistar Albino rats. Thirty male rats were arbitrarily sorted into three groups of ten animals each. The control group received a normal saline for 18 days. The MTX (induction) group received MTX (25 mg/kg) intraperitoneally on the 7th day of the experiment once daily for 6 consecutive days. The MTX + BOS group received BOS (50 mg/kg) orally once a day for 18 days: 6 days before induction, 6 days 2-h after induction, and 6 days post-induction. Animals were euthanized on day 19, and salivary gland tissues were dissected for biochemical, histopathological, and immunohistochemical analyses. BOS dramatically improved MTX-aggravated biochemical and histopathological abnormalities, as evidenced by diminished Bax, caspase 3, TNF-α, IL-1β, MDA, and MPO levels, increased SOD, GSH, and GPX levels, and reduced degenerative changes in the granular convolute tubule, mucous acini, and striate duct. BOS further substantially upregulated MTX-induced decline of the Ki-67 and Bcl-2, as indicated by immunohistochemistry scoring methods. The anti-oxidative, ant-inflammatory, and antiapoptotic properties of BOS are a promising strategy for ameliorating the toxic effect of MTX on submandibular glandular tissues.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf007"},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996599","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":"Mutagenicity and carcinogenicity prediction of sugar substitutes: an <i>in silico</i> approach with compound-gene interactions network.","authors":"Charli Deepak Arulanandam, Venkatadri Babu, Yugendhar Soorni, Ragothaman Prathiviraj","doi":"10.1093/toxres/tfaf008","DOIUrl":"10.1093/toxres/tfaf008","url":null,"abstract":"<p><p>Sugar substitutes are mostly artificial, man-made industrial products used as additives in food and beverages. Most of these substances flow through the digestive tract and food chains, becoming emerging organic contaminants in various abiotic and biotic environmental media. Here, we predict the mutagenicity and carcinogenicity of commonly used sugar substitutes using in silico based methods. The simplified molecular-input line-entry system (SMILES) of sugar substitutes was obtained from the PubChem database for toxicity predictions. Here, sixteen sugar substitutes tested out of these four compounds Glucin (GLU), and 5-nitro-2-propoxyaniline (P-4000), SCL, Ace were predicted as mutagens by using in silico tools such as LAZAR, pKCSM, and Toxtree. Based on the predicted results GLU and P-4000 were predicted as carcinogenic sugar substitutes. Also the study conducted compound gene interaction network to identify the direct connection between sugar substitutes and its corresponding receptors.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf008"},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996596","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}
Toxicology ResearchPub Date : 2025-01-17eCollection Date: 2025-02-01DOI: 10.1093/toxres/tfaf005
Biao Zhou, Wei Li, Zhiqiang Luo, Liguo Zhu, Jie Yu, Yuxing Guo, Wangyang Li, Hui Xiong, Xiaolong Lu
{"title":"Therapeutic effects and mechanisms of Juanbilijieqing fang in ameliorating gouty arthritis in a murine model.","authors":"Biao Zhou, Wei Li, Zhiqiang Luo, Liguo Zhu, Jie Yu, Yuxing Guo, Wangyang Li, Hui Xiong, Xiaolong Lu","doi":"10.1093/toxres/tfaf005","DOIUrl":"10.1093/toxres/tfaf005","url":null,"abstract":"<p><p>This study aims to assess the safety, efficacy, and mechanisms of Juanbilijieqing Fang in a mouse model of gouty arthritis. C57BL/6 mice were allocated into six groups: control, gouty arthritis model, and treatment groups receiving varying doses of Juanbilijieqing Fang (low, medium, high), along with a positive control group treated with febuxostat. Gouty arthritis was induced via MSU crystal injection following a high-fat diet. Mice were treated with Juanbilijieqing Fang or febuxostat, and safety was evaluated by measuring spleen, kidney, and liver indices. Efficacy was assessed by monitoring foot thickness, pain threshold, and biochemical markers, including serum uric acid (UA), myeloperoxidase (MPO), xanthine oxidase (XOD), and adenosine deaminase (ADA). Serum pro-inflammatory cytokines were analyzed, and intestinal inflammation and barrier integrity were examined through histological and molecular assays. Juanbilijieqing Fang did not significantly affect spleen, kidney, or liver indices, indicating its safety. Therapeutically, it significantly reduced foot swelling, improved pain threshold, and decreased serum uric acid levels. It also lowered MPO activity in foot tissue and reduced XOD and ADA activity in the liver. Additionally, the formula downregulated pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ, demonstrating a strong anti-inflammatory effect. It ameliorated gut inflammation by decreasing NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1) and enhanced gut mucosal integrity by upregulating ZO-1 and Occludin expression. Juanbilijieqing Fang is a safe and effective treatment for gouty arthritis, primarily through reducing systemic and intestinal inflammation and restoring gut barrier function.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf005"},"PeriodicalIF":2.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996601","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}
Toxicology ResearchPub Date : 2025-01-14eCollection Date: 2025-02-01DOI: 10.1093/toxres/tfae233
Wei Ding, Kun Qian, Wenxiu Bao, Zhen Wang
{"title":"Phellodendrine inhibits oxidative stress and promotes autophagy by regulating the AMPK/mTOR pathway in burn sepsis-induced intestinal injury.","authors":"Wei Ding, Kun Qian, Wenxiu Bao, Zhen Wang","doi":"10.1093/toxres/tfae233","DOIUrl":"10.1093/toxres/tfae233","url":null,"abstract":"<p><p>Intestinal injury is an important complication of burn sepsis with limited therapeutic choices. Phellodendrine is a promising compound for gastrointestinal inflammatory diseases and is extracted from the traditional Chinese medicine phellodendron bark. The study aimed to explore the role of phellodendrine against oxidative stress and autophagy in burn sepsis-induced intestinal injury. A mouse model of burn sepsis model was established by intraperitoneally injecting 10 mg/kg lipopolysaccharide (LPS) to mice burned by boiled water. Phellodendrine (30 mg/kg) was injected into mice in the drug group after scalding and before LPS injection. Hematoxylin and eosin staining was performed to observe histopathological changes in murine small intestines. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was performed to evaluate intestinal cell apoptosis. Immunofluorescence staining was performed to measure the expression and distribution of autophagy markers, light chain 3II (LC3II) and p62 in intestinal tissues. Oxidative stress indicators were detected using corresponding commercial kits. Protein levels of apoptotic markers, autophagy markers, and factors involved in adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathway in intestines were quantified by western blotting. Phellodendrine attenuated bun sepsis-induced intestinal pathological changes. Meanwhile, aggravated cell apoptosis, reduction of antioxidant enzymes, and downregulation of autophagy markers in intestinal tissues of burn sepsis group were all improved by phellodendrine. In addition, phellodendrine activated the phosphorylation (p) of AMPK and inhibited p-mTOR signaling in intestines of burn septic mice. In conclusion, phellodendrine suppresses oxidative stress and activates autophagy in burn sepsis-induced intestinal injury by activating AMPK and inhibiting mTOR signaling.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae233"},"PeriodicalIF":2.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996598","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}
Toxicology ResearchPub Date : 2025-01-12eCollection Date: 2025-02-01DOI: 10.1093/toxres/tfaf004
Laurent Gaté, Sylvie Sébillaud, Mylène Lorcin, Carole Seidel, Christian Darne
{"title":"Influence of macrophages and neutrophilic granulocyte-like cells on crystalline silica-induced toxicity in human lung epithelial cells.","authors":"Laurent Gaté, Sylvie Sébillaud, Mylène Lorcin, Carole Seidel, Christian Darne","doi":"10.1093/toxres/tfaf004","DOIUrl":"10.1093/toxres/tfaf004","url":null,"abstract":"<p><p>In many industrial activities, workers may be exposed by inhalation to particles that are aerosolized, To predict the human health hazard of these materials, we propose to develop a co-culture model (macrophages, granulocytes, and alveolar epithelial cells) designed to be more representative of the inflammatory pulmonary response occurring in vivo. Phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells were used as macrophages, All-trans retinoic acid (ATRA)-differentiated HL60 were used as granulocytes and A549 were used as epithelial alveolar type II cells. A crystalline silica sample DQ12 was used as a prototypical particle for its capabilities to induce DNA damage, inflammatory response, and oxidative stress in epithelial cells; its polyvinylpyridine-N-oxide (PVNO)-surface modified counterpart was also used as a negative particulate control. Cells in mono-, bi- or tri-culture were exposed to DQ12 or DQ12-PVNO for 24 h. DQ12 but not DQ12-PVNO induced a significant increase in DNA damage in A549 cells. The presence of differentiated THP-1 reduced the genotoxic effects of this crystalline silica sample. The exposure of A549 to DQ12 but not DQ12-PVNO induced a significant change in interleukin-8 (IL-8) protein levels which was exacerbated when differentiated THP-1, and HL-60, were added. In addition, while no production of TNFα was detected in the A549 monoculture, elevated levels of this cytokine were observed in the co-culture systems. This work shows that a cell culture model that takes into consideration the complexity of the pulmonary inflammatory response might be more dependable to study the toxicological properties of particles than \"simple\" monoculture models.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf004"},"PeriodicalIF":2.2,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996594","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}
Toxicology ResearchPub Date : 2025-01-12eCollection Date: 2025-02-01DOI: 10.1093/toxres/tfaf001
Charlotte Lacroix-Durand, David Janz, Karsten Liber
{"title":"Chronic Radium-226 toxicity to and oxidative stress in the aquatic invertebrate <i>Chironomus dilutus</i>.","authors":"Charlotte Lacroix-Durand, David Janz, Karsten Liber","doi":"10.1093/toxres/tfaf001","DOIUrl":"10.1093/toxres/tfaf001","url":null,"abstract":"<p><p>The mining industry, including uranium mining and milling, is of high importance in Canada. It is, however, important to consider that ore processing can result in the creation of by-products that contain radionuclides such as radium-226 (<sup>226</sup>Ra). Even with the strict discharge regulations in place, there is limited evidence to suggest that the current Canadian regulatory thresholds for <sup>226</sup>Ra are protective for aquatic life. This concern underscores the importance of generating toxicity data for <sup>226</sup>Ra, as no federal Canadian water quality guidelines for <sup>226</sup>Ra currently exist to safeguard aquatic ecosystems. The potential ecological risks of <sup>226</sup>Ra are significant due to its high mobility under typical environmental conditions, long half-life (t<sub>1/2</sub> ~ 1,600 years), bioaccumulative properties, and similarity to calcium (Ca<sup>2+</sup>). Considering this, the primary objective of this research was to gather data on the toxicity of <sup>226</sup>Ra to the aquatic invertebrate <i>Chironomus dilutus</i>. For this purpose, a partial life cycle experiment was conducted, with larval growth, survival and pupation, and emergence and sex ratio of emerged adults, as the experimental endpoints. In addition, an assessment of oxidative stress as a potential cause of toxicity was performed. These experiments revealed that elevated activity concentrations of <sup>226</sup>Ra (25.5 Bq/L) can significantly impact the growth of <i>C. dilutus.</i> However, none of the other nonlethal endpoints were significantly affected by <sup>226</sup>Ra exposure, and there was no evidence of oxidative stress in exposed <i>C. dilutus</i>. Finally, <sup>226</sup>Ra was shown to adsorb onto the silica sand used as a substrate for all experiments and desorbed following acid extraction.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf001"},"PeriodicalIF":2.2,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996591","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}
Toxicology ResearchPub Date : 2025-01-09eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae231
Kunyu Du, Jingkui Shu, Jintao Wu, Na Liu, He Ma, Jinyun Jiang, Yuefeng He, Xinan Wu
{"title":"Inorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway.","authors":"Kunyu Du, Jingkui Shu, Jintao Wu, Na Liu, He Ma, Jinyun Jiang, Yuefeng He, Xinan Wu","doi":"10.1093/toxres/tfae231","DOIUrl":"10.1093/toxres/tfae231","url":null,"abstract":"<p><p>This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA). The results showed that silencing AGO2 not only reduced cell viability but also intensified apoptosis, highlighting its role in activating the p53 pathway. This was further supported by increased phosphorylation of p53 at Ser392 and Thr55, reinforcing AGO2's involvement in apoptotic processes. The study underscores the potential of AGO2 as a therapeutic target in arsenic-related pathologies and highlights the critical need for managing occupational exposure to arsenic.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae231"},"PeriodicalIF":2.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968818","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}
Toxicology ResearchPub Date : 2025-01-08eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae235
Linsen Zhang, Xiu Yuan, Qingmei Peng
{"title":"Therapeutic potential of <i>Achillea millefolium</i> L. extract on 7,12-dimethylbenz(a)anthracene (DMBA) -induced ovary cancer in Wistar rats: a biochemical, molecular and histopathological approach.","authors":"Linsen Zhang, Xiu Yuan, Qingmei Peng","doi":"10.1093/toxres/tfae235","DOIUrl":"10.1093/toxres/tfae235","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a significant cause of cancer-related mortality among women. This study explores the efficacy of <i>Achillea millefolium</i> L. (<i>A. millefolium</i>) extract, known for its phytoestrogenic properties, in treating OC through hormonal and metabolic modulation. Using a Wistar rat model, OC was induced with 7,12-dimethylbenz(a)anthracene (DMBA), and the effects of <i>A. millefolium</i>, both alone and in combination with paclitaxel (PTX), were evaluated. The study involved five groups of ten rats each: normal, OC, and those receiving 100 mg/kg of <i>A. millefolium</i> with or without PTX. Key hormonal levels, oxidative stress markers, and inflammatory cytokines were measured. Additionally, ovarian tissues were analyzed for malondialdehyde and ferric reducing ability of plasma, while gene and protein expressions related to apoptosis were assessed. Results showed that <i>A. millefolium</i>, particularly when combined with PTX, reduced the luteinizing hormone/follicle-stimulating hormone ratio, increased antioxidant enzyme activity, and upregulated apoptosis-related pathways, leading to higher p53 expression and fewer Ki-67 positive cells. These findings suggest <i>A. millefolium</i>'s potential as a complementary therapy for women with OC, particularly those with ovulation disorders.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae235"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941506","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}
Toxicology ResearchPub Date : 2025-01-08eCollection Date: 2025-01-01DOI: 10.1093/toxres/tfae234
Sarah S Mohammed, Ayman Zaaqoq, Shimaa Talaat, Salma I Abdelkader
{"title":"A randomized, clinical trial of intravenous N-acetylcysteine as an antioxidant therapy in acute organophosphorus pesticide poisoning.","authors":"Sarah S Mohammed, Ayman Zaaqoq, Shimaa Talaat, Salma I Abdelkader","doi":"10.1093/toxres/tfae234","DOIUrl":"10.1093/toxres/tfae234","url":null,"abstract":"<p><p>The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned. A randomized, controlled, parallel-group trial was conducted in the period from the beginning of January 2022 to the end of June 2022. The study included 56 acute OP poisoned patients admitted to the intensive care unit (ICU) at the Poison Control Center of Ain Shams University Hospitals within 6 h after the exposure. The patients were randomly allocated in two equal groups; group (A): received the standard treatment plus NAC in a total dose of 300 mg/kg administered intravenously (IV) while group (B) received the standard treatment. Then both groups were compared as regards clinical parameters, laboratory investigations, ECG, and outcomes. Baseline parameters were comparable between the groups. However, NAC treatment significantly elevated concentrations of both serum catalase and glutathione peroxidase levels at 24 h, it did not significantly affect the total dose of atropine required, duration of atropine and oximes treatment or need for mechanical ventilation, and length of hospital stay. Mortality was lower in the NAC group (2 out of 28) than the standard treatment-only group (5 out of 28) but the difference was not statistically significant. This trial found that NAC improved antioxidant enzyme levels including serum CAT and GPX but did not affect clinically relevant outcomes.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae234"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941792","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":"Up-regulation of miR-490-3p improves learning/memory disability of sevoflurane exposure by relieving neuroinflammation.","authors":"Shuang Zhai, Ying Li, Aili Guo, Wei Zhao, Changliang Mou","doi":"10.1093/toxres/tfae226","DOIUrl":"10.1093/toxres/tfae226","url":null,"abstract":"<p><p>Our study focused on the potential mechanism of microRNA-490-3p (miR-490-3p) on learning/memory disability of rats resulting from sevoflurane (Sev). The rat model of cognitive dysfunction was established by infection with miR-490-3p mimic and Sev-exposure. Morris water maze and open field test assay were used for the assessment of cognitive deficits. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction assays were used for the measurements of neuroinflammatory cytokines and inflammatory-related genes in respective order. Bioinformatics analysis was employed for the predictive miR-490-3p-related genes. The targeted interaction was verified via dual-luciferase reporter assay. A significant decline of miR-490-3p was discovered in rats with Sev treatment, while the levels were up-regulated in rats with infection miR-490-3p pretreatment (<i>P</i> < 0.001). For Sev-induced rats, the stay time in the target quadrant was shorten, while distance travelled lengthened significantly with the control group by comparison (<i>P</i> < 0.001). Notably, an increased time of the escape latency and a decreased number of platform crossings were found in the Sev group, which alleviated by infection with miR-490-3p mimic pretreatment (<i>P</i> < 0.001). Moreover, the neuroinflammatory cytokines were elevated in the Sev group, the effects of which were recovered via miR-490-3p pretreatment (<i>P</i> < 0.001). Bioinformatics analysis predicted the miR-490-3p-associated genes. CDK1 (Cyclin-dependent kinase 1) was a potential target gene of miR-490-3p, which confirmed by dual-luciferase reporter detection. MiR-490-3p alleviated the learning and memory deficits in Sev-treated rats via the modulation of CDK1.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae226"},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941509","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}