Toxicology Research最新文献

{"title":"Overexpression of DTX1 inhibits D-GalN/TNF-α-induced pyroptosis and inflammation in hepatocytes by regulating NLRP3 ubiquitination.","authors":"Mingshui Liu, Jing Gu, Li Chen, Wei Sun, Xiaoping Huang, Jianhe Gan","doi":"10.1093/toxres/tfae145","DOIUrl":"https://doi.org/10.1093/toxres/tfae145","url":null,"abstract":"<p><strong>Background: </strong>Acute liver injury (ALI) is characterized by massive hepatocyte death and has high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the pathophysiology of ALI and is involved in the inflammatory response mediated by NOD-like receptor protein 3 (NLRP3) inflammasome activation. Deltex 1 (DTX1) is a single transmembrane protein with ubiquitin E3 ligase activity and is closely involved in cell growth, differentiation, and apoptosis, as well as intracellular signal transduction. However, little is known about the influence of DTX1 on ALI. This study aimed to investigate the role of DTX1 in pyroptosis and inflammation induced by D-galactosamine (D-GalN) and tumor necrosis factoralpha (TNF-α) in human hepatocytes (LO2 cells) in vitro.</p><p><strong>Methods: </strong>Cell pyroptosis was measured by flow cytometry. The levels of DTX1, pyroptosis-associated proteins, and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Immunofluorescence staining, co-immunoprecipitation, ubiquitination, and luciferase reporter and chromatin immunoprecipitation assays were performed to detect the regulation between DTX1 and NLRP3 or hepatocyte nuclear factor 4 alpha (HNF4α). Analysis of variance was performed to compare groups.</p><p><strong>Results: </strong>We found that DTX1 was decreased in D-GalN/TNF-α-induced LO2 cells. DTX1 overexpression significantly inhibited D-GalN/TNF-α-induced cell pyroptosis and inflammation. DTX1 interacted with NLRP3 and induced NLRP3 ubiquitination and degradation. Furthermore, by targeting NLRP3, DTX1 knockdown significantly induced cell pyroptosis and inflammation. In addition, HNF4α promoted DTX1 transcription by binding with its promoter.</p><p><strong>Conclusion: </strong>Our study revealed that DTX1 suppressed D-GalN/TNF-α-induced hepatocyte pyroptosis and inflammation by regulating NLRP3 ubiquitination.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae145"},"PeriodicalIF":2.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337533","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":"Urinary kallikrein reverses neuropathic pain by inhibiting ectopic neural discharges, neural inflammation and oxidative stress.","authors":"Mingsheng Chen, Jinze Wu, Yafei Gao, Yunlei Li, Shiming He, Jungong Jin","doi":"10.1093/toxres/tfae146","DOIUrl":"https://doi.org/10.1093/toxres/tfae146","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain is a refractory disease and badly impacts the lives of patients. Urinary kallikrein (UK) acted as a glycoprotein has been discovered to play a pivotal role in neuroprotection. However, the regulatory impacts and correlative pathways of UK in the progression of neuropathic pain remain dimness.</p><p><strong>Methods: </strong>The chronic constriction injury (CCI) rat model was firstly established to mimic neuropathic pain. The withdrawal threshold was measured through the Von Frey test. The levels of TNF-α, IL-1β and IL-6 were determined through ELISA. The levels of ROS, GSH, SOD and GSH-Px were examined through the commercial kits. The ectopic discharges were assessed. The protein expressions were inspected through western blot.</p><p><strong>Results: </strong>It was demonstrated that withdrawal threshold was reduced in CCI rat model, but this change was reversed after UK treatment, indicating that UK relieved mechanical allodynia. Moreover, UK alleviated the inflammatory response through reducing TNF-α, IL-1β and IL-6 levels. It was uncovered that oxidative stress was strengthened in CCI rat model, but this impact was restrained after UK treatment. Additionally, UK suppressed ectopic discharge. At last, it was proved that UK triggered the Nrf2/ARE signaling pathway in CCI rat model.</p><p><strong>Conclusion: </strong>This study manifested that UK reversed neuropathic pain by inhibiting ectopic neural pathways, neural pathways and oxidation via the Nrf2/ARE pathway. This study may offer useful proofs the regulatory functions of UK in the cure of neuropathic pain.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae146"},"PeriodicalIF":2.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337534","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":"Neurotoxic effects associated with chronic inhalation and oral exposure to glyphosate-based herbicide IN adult rats.","authors":"Renata M S Bifaroni, Giovanna D Binotti, Karen P Bruneri, Maria Eduarda A Tavares, Rose Meire R Ueda, Renata C Rossi, Giovana R Teixeira, Camila Renata Corrêa, Gisele Alborghetti Nai","doi":"10.1093/toxres/tfae148","DOIUrl":"https://doi.org/10.1093/toxres/tfae148","url":null,"abstract":"<p><p>The use of glyphosate-based herbicides (GBHs) for agricultural production has increased substantially around the world, as have their residues in the environment. Its effects on the central nervous system and neurotoxicity pathways are still not fully understood. The aim of this study was to evaluate the neurotoxic effect of chronic exposure to a GBH in adult rats. Sixty adult male albino Wistar rats were allocated into 6 groups, 2 control groups, and four GBH exposure groups (n = 10/group). The animals were exposed to two concentrations of GBH, orally and by inhalation: 2.99 × 10^-3 grams of active ingredient per hectare (g.a.i./ha) and 7.48 × 10^-3 g.a.i./ha. The animals were exposed for six months. Behavioral studies were performed. Brain tissue was collected for histopathological, immunohistochemical, and oxidative stress analyses. Animals exposed by inhalation to GBH spent more time in the central area of the open field test, whereas animals exposed to a high oral concentration of GBH spent less time in the open arms in the elevated plus-maze test. Tissue hyperemia occurred only in animals exposed to high concentrations of GBH. There was a greater thickness of the cerebral cortex and an increase in the expression of the BCL-2 in the animals exposed by inhalation to GBH. There was no difference in the doses of malonaldehyde and protein carbonylation between exposed and unexposed groups. The exposure to GBH caused increased levels of anxiety, regardless of the route, high concentrations caused hyperemia and inhalation exposure cause increased cortex thickness and increased BCl-2 expression.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae148"},"PeriodicalIF":2.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337531","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":"Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review.","authors":"Yun Gu, Ying Qiu, Yujian Li, Weihua Wen","doi":"10.1093/toxres/tfae136","DOIUrl":"10.1093/toxres/tfae136","url":null,"abstract":"<p><p>As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae136"},"PeriodicalIF":2.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054297","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":"Assessment of cytoprotective and genoprotective effects of <i>Moringa oleifera</i> and <i>Tinospora cordifolia</i> extracts in vitro.","authors":"Preeti Bagri, Vinod Kumar, Kanisht Batra","doi":"10.1093/toxres/tfae133","DOIUrl":"10.1093/toxres/tfae133","url":null,"abstract":"<p><strong>Background: </strong><i>Moringa oleifera</i> and <i>Tinospora cordifolia</i> is extensively used as an ingredient of food and in traditional medicine for the management of a variety of diseases.</p><p><strong>Material and methods: </strong>The extracts of leaf of <i>Moringa oleifera</i> and stem of <i>Tinospora cordifolia</i> were assessed to examine their ability to inhibit the oxidative DNA damage (by DNA protection assay), cytoprotective and genoprotective potential (by Comet assay) in V79 cells individually and in combinations.</p><p><strong>Result: </strong>It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA. <i>M. oleifera</i> extract (160 and 320 μg/mL) and <i>Tinospora cordifolia</i> extract (640, 1,280 and 2,560 μg/mL) individually showed higher DNA protection activity. <i>M. oleifera</i> (1,280 μg/mL) combined with <i>Tinospora cordifolia</i> (640 μg/mL) showed best cytoprotective and genoprotective activities among different concentration combinations and various concentrations of individual plants in V79 cell line against hydrogen peroxide induced cytotoxicity and genotoxicity.</p><p><strong>Conclusion: </strong>This study demonstrates the cytoprotective and genoprotective activity of M. oleifera and Tinospora cordifolia individually or in combination.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae133"},"PeriodicalIF":2.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054296","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":"Low expression of Lnc-ENST00000535078 inhibits the migration, invasion, and enhances apoptosis of CTPE-induced malignantly transformed BEAS-2B cells.","authors":"Ping Lu, Liu Yang, Yanting Lei, Yuezeng Zhao, Zhihao Tang, Pingping Shang, Xiaolei Zhou, Pengpeng Wang, Wei Wang, Feifei Feng, Qiao Zhang","doi":"10.1093/toxres/tfae121","DOIUrl":"10.1093/toxres/tfae121","url":null,"abstract":"<p><p>Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae121"},"PeriodicalIF":2.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034615","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":"Ameliorative impacts of Sinapic acid against monosodium urate crystal-induced gouty arthritis and inflammation through different signaling pathways.","authors":"Muhammad Ishaq, Liang Zhao, Mohamed Mohamed Soliman, Saed Althobaiti, Helal F Al-Harthi, Shatha B Albattal, Wang Chengtao","doi":"10.1093/toxres/tfae130","DOIUrl":"10.1093/toxres/tfae130","url":null,"abstract":"<p><p>As known, gout a metabolic disease due to the urate crystals deposition in the joints and affect human health and state. Humans are looking for safe natural remedies from plants with safe, low cost and high effect on their health. Sinapic acid (SA) is found in plants and used as phytoconstituent in human diets. SA has strong antioxidant activity, bone-regenerative, anti-cancer, anti-allergic, and antidiabetic effects. The current study was outlined to confirm the anti-gout potential of SA against monosodium urate crystals (MSU)-induced gouty arthritis in mice. Positive gouty arthritis was conducted by administration of colchicine and MSU in the hind paw. SA was orally administered to negative and positive MSU arthritic mice at 25 and 50 mg/kg, one-hour before MSU injection (100 μg/kg intra-articular). At the end of the experiment, sampling was done for serum, histopathology, oxidative stress and gene expression analysis. The results showed that SA significantly recovered the joint edema and recovered MSU crystals-showed histopathological changes. The production of cytokines, leukocyte recruitment, oxidative stress, and nucleotide-binding domain, leucinerich-containing family, pyrin domain-containing-3 (NLRP3)-inflammasome genes expressions were increased in positive arthritic mice and ameliorated significantly by SA administration. Moreover, SA showed ameliorative impacts on air pouch model of mice as reported by the down regulation in the expression of inflammation related blood cells, proinflammatory cytokines and other transcriptional genes. In conclusion, sinapic acid showed a potential therapeutic use against side effects accompanying gouty arthritis and is good as a supplement against inflammation associated disorders.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae130"},"PeriodicalIF":2.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034614","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":"Orlistat and metformin combination ameliorates obesity-induced renal injury via suppressing renal oxidative stress in male rats.","authors":"Khadeejah Alsolami, Reham Z Hamza","doi":"10.1093/toxres/tfae135","DOIUrl":"10.1093/toxres/tfae135","url":null,"abstract":"<p><strong>Background: </strong>Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS).</p><p><strong>Objectives: </strong>Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress.</p><p><strong>Methods: </strong>Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues.</p><p><strong>Results: </strong>The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group.</p><p><strong>Conclusion: </strong>The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae135"},"PeriodicalIF":2.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034616","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":"Anti-oxidant activity of coenzyme Q10 against AlCl₃/D-galactose in albino rat induced cognitive dysfunctions: Behavioral, biochemical, and BACE-1/GSK-3β alterations.","authors":"Nagat Fawzy Nawar, Doha Mohammad Beltagy, Tarek Mostafa Mohamed, Ehab Mostafa Tousson, Mai Mahmoud El-Keey","doi":"10.1093/toxres/tfae131","DOIUrl":"10.1093/toxres/tfae131","url":null,"abstract":"<p><p>The relationship between amyloid beta (Aβ) and oxidative stress (OS), both prominent factors in Alzheimer's disease-related neural degeneration, is deeply interconnected. The cleavage of the extracellular domain of Amyloid precursor protein (APP) and phosphorylating different substrates, respectively, the β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) and Glycogen synthase kinase-3-beta (GSK-3β) enzymes initiate the synthesis of Aβ, which causes cognitive deficits in AD. This study aimed to explore the protective potential of Coenzyme Q10 (CoQ10). It also sought to uncover any synergistic effects when combined with donepezil, an acetylcholinesterase inhibitor, in treating Alzheimer's disease in male albino rats, focusing on the modulation of the BACE-1/GSK-3β pathway. The experiment involved 70 rats categorized into different groups: control, donepezil alone, CoQ10 alone, AD-model, donepezil co-treatment, CoQ10 co-treatment, and CoQ10 + donepezil combination. Various assessments, such as cholinesterase activity, oxidative stress, serum iron profile, Brain Derived Neurotrophic Factor (BDNF), Tau protein, β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), phosphatase and tensin homolog (Pten), and Glycogen synthase kinase-3-beta (GSK-3β), were conducted on behavioral and biochemical aspects. CoQ10 treatment demonstrated memory improvement, enhanced locomotion, and increased neuronal differentiation, mainly through the inhibition of the dual BACE-1/GSK-3β. These findings were substantiated by histological and immunohistological examinations of the hippocampus.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae131"},"PeriodicalIF":2.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007882","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":"Silencing CircHIPK3 improves sevoflurane-explore learning and memory dysfunction and nerve damage via enhancing miR-338-3p.","authors":"Xiuli Li, Xuefei Li, Yinan Liang","doi":"10.1093/toxres/tfae132","DOIUrl":"10.1093/toxres/tfae132","url":null,"abstract":"<p><strong>Background: </strong>Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory.</p><p><strong>Objective: </strong>This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment.</p><p><strong>Methods: </strong>SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p.</p><p><strong>Results: </strong>Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions . silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p.</p><p><strong>Conclusion: </strong>Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 4","pages":"tfae132"},"PeriodicalIF":2.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007883","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}