Toxicological Research最新文献

{"title":"Dual oxidative stress and fatty acid profile impacts in <i>Paracentrotus lividus</i> exposed to lambda-cyhalothrin: biochemical and histopathological responses.","authors":"Chaima Fouzai, Wafa Trabelsi, Safa Bejaoui, Michel Marengo, Feriel Ghribi, Imen Chetoui, Sami Mili, Nejla Soudani","doi":"10.1007/s43188-023-00174-4","DOIUrl":"10.1007/s43188-023-00174-4","url":null,"abstract":"<p><p>Lambda-cyhalothrin (λ-cyh) is a potential pyrethroid insecticide widely used in pest control. The presence of pyrethroids in the aquatic ecosystem may induce adverse effects on non-target organisms such as the sea urchin. This study was conducted to assess the toxic effects of λ-cyh on the fatty acid profiles, redox status, and histopathological aspects of <i>Paracentrotus lividus</i> gonads following exposure to three concentrations of λ-cyh (100, 250 and 500 µg/L) for 72 h. The results showed a significant decrease in saturated fatty acid (SFAs) with an increase in monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) levels in λ-cyh treated sea urchins. The highest levels in PUFAs were recorded in the eicosapentaenoic acids (C20:5n-3), docosahexaenoic acids (C22:6n-3) and arachidonic acids (C20:4n-6) levels. The λ-cyh intoxication promoted oxidative stress with an increase in hydrogen peroxide (H₂O₂), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels. Furthermore, the enzymatic activities and non-enzymatic antioxidants levels were enhanced in all exposed sea urchins, while the vitamin C levels were decreased in 100 and 500 µg/L treated groups. Our biochemical results have been confirmed by the histopathological observations. Collectively, our findings offered valuable insights into the importance of assessing fatty acids' profiles as a relevant tool in aquatic ecotoxicological studies.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"429-441"},"PeriodicalIF":1.6,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737593","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":"Immunodysregulatory potentials of polyethylene or polytetrafluorethylene microplastics to mice subacutely exposed via intragastric intubation.","authors":"JiHun Jo, Manju Acharya, Pramod Bahadur K C, Anju Maharjan, DaEun Lee, Ravi Gautam, Jung-Taek Kwon, KilSoo Kim, ChangYul Kim, Yong Heo, HyoungAh Kim","doi":"10.1007/s43188-023-00172-6","DOIUrl":"10.1007/s43188-023-00172-6","url":null,"abstract":"<p><p>Microplastics (MPs) have been recently recognized as posing a risk to human health. The adverse health effects of MP exposure have been recently reported, especially via the oral exposure route. The present study investigated whether subacute (4 week) exposure to polyethylene (PE) or polytetrafluorethylene (PTFE) MPs via gastric intubation caused immunotoxicity. Two different sizes of PE MPs (6.2 or 27.2 μm) and PTFE MPs (6.0 or 30.5 μm) were administered to 6-week-old mice of both sexes at 0 (corn oil vehicle control), 500, 1000, or 2000 mg/kg/day (n = 4/group). No significant differences were observed between groups in the major thymic or splenic immune cell populations, including thymic CD4⁺, CD8⁺, CD4⁺/CD8⁺ T lymphocytes, and splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-gamma (IFNγ) to interleukin-4 (IL-4) in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo (48 h) was dose-dependently decreased in female mice that received small- and large-size PTFE MPs. The IFNγ/IL-4 ratio was also decreased in the female mice dosed with large-size PE MPs. The serum IgG2a/IgG1 ratio was dose-dependently increased in male and female animals dosed with small-size PE MPs, in female animals dosed with large-size PTFE MPs, and in male animals dosed with small-size PTFE MPs. The present study implies that immune functions could be affected in animals exposed to MPs via gastric intubation. These effects are dependent on MP size, MP dose, MP polymer type, and mouse sex. Further investigations with longer exposure periods could be necessary to more clearly define the immunotoxic effects of MPs.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-023-00172-6.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"419-427"},"PeriodicalIF":1.6,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749091","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":"Toxicologic pathological mechanism of acute lung injury induced by oral administration of benzalkonium chloride in mice.","authors":"Hidehisa Sekijima, Toru Oshima, Yuno Ueji, Naoko Kuno, Yukino Kondo, Saera Nomura, Tomomi Asakura, Kae Sakai-Sugino, Mitsuo Kawano, Hiroshi Komada, Hirokazu Kotani","doi":"10.1007/s43188-023-00178-0","DOIUrl":"10.1007/s43188-023-00178-0","url":null,"abstract":"<p><p>Benzalkonium chloride (BAC) intoxication causes fatal lung injuries, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the pathogenesis of ALI/ARDS induced by BAC ingestion is poorly understood. This study aimed to clarify the mechanism of lung toxicity after BAC ingestion in a mouse model. BAC was orally administered to C57BL/6 mice at doses of 100, 250, and 1250 mg/kg. After administration, BAC concentrations in the blood and lungs were evaluated via liquid chromatography with tandem mass spectrometry. Lung tissue injury was evaluated via histological and protein analyses. Blood and lung BAC concentration levels after oral administration increased in a dose-dependent manner, with the concentrations directly proportional to the dose administered. The severity of lung injury worsened over time after the oral administration of 1250 mg/kg BAC. An increase in the terminal transferase dUTP nick end labeling-positive cells and cleaved caspase-3 levels was observed in the lungs after 1250 mg/kg BAC administration. In addition, increased cleaved caspase-9 levels and mitochondrial cytochrome c release into the cytosol were observed. These results suggest that lung tissue injury with excessive apoptosis contributes to BAC-induced ALI development and exacerbation. Our findings provide useful information for developing an effective treatment for ALI/ARDS induced by BAC ingestion.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"409-418"},"PeriodicalIF":1.6,"publicationDate":"2023-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749092","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":"A comparative study on the implementation of deep learning algorithms for detection of hepatic necrosis in toxicity studies.","authors":"Ji-Hee Hwang,&nbsp;Minyoung Lim,&nbsp;Gyeongjin Han,&nbsp;Heejin Park,&nbsp;Yong-Bum Kim,&nbsp;Jinseok Park,&nbsp;Sang-Yeop Jun,&nbsp;Jaeku Lee,&nbsp;Jae-Woo Cho","doi":"10.1007/s43188-023-00173-5","DOIUrl":"10.1007/s43188-023-00173-5","url":null,"abstract":"<p><p>Deep learning has recently become one of the most popular methods of image analysis. In non-clinical studies, several tissue slides are generated to investigate the toxicity of a test compound. These are converted into digital image data using a slide scanner, which is then studied by researchers to investigate abnormalities, and the deep learning method has been started to adopt in this study. However, comparative studies evaluating different deep learning algorithms for analyzing abnormal lesions are scarce. In this study, we applied three algorithms, SSD, Mask R-CNN, and DeepLabV3⁺, to detect hepatic necrosis in slide images and determine the best deep learning algorithm for analyzing abnormal lesions. We trained each algorithm on 5750 images and 5835 annotations of hepatic necrosis including validation and test, augmented with 500 image tiles of 448 × 448 pixels. Precision, recall, and accuracy were calculated for each algorithm based on the prediction results of 60 test images of 2688 × 2688 pixels. The two segmentation algorithms, DeepLabV3⁺ and Mask R-CNN, showed over 90% of accuracy (0.94 and 0.92, respectively), whereas SSD, an object detection algorithm, showed lower accuracy. The trained DeepLabV3⁺ outperformed all others in recall while also successfully separating hepatic necrosis from other features in the test images. It is important to localize and separate the abnormal lesion of interest from other features to investigate it on a slide level. Therefore, we suggest that segmentation algorithms are more appropriate than object detection algorithms for use in the pathological analysis of images in non-clinical studies.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-023-00173-5.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"399-408"},"PeriodicalIF":2.3,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10300369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (<i>Raja kenojei</i>) skin: a rat model study.","authors":"Heung-Sik Seo, Jun-Ho Kim, Sang-Ho Kim, Myeong-Kyu Park, Nak-Won Seong, Geun-Hee Kang, Joong-Sun Kim, Sung-Ho Kim, Jong-Choon Kim, Changjong Moon","doi":"10.1007/s43188-023-00175-3","DOIUrl":"10.1007/s43188-023-00175-3","url":null,"abstract":"<p><p>Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (<i>Raja kenojei</i>) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"383-398"},"PeriodicalIF":1.6,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749089","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":"Effects of stabilizer magnesium nirate on CMIT/MIT-induced respiratory toxicity.","authors":"Mi-Kyung Song,&nbsp;Yong-Wook Baek,&nbsp;Dong Im Kim,&nbsp;Sung-Hoon Yoon,&nbsp;Kyuhong Lee","doi":"10.1007/s43188-023-00170-8","DOIUrl":"10.1007/s43188-023-00170-8","url":null,"abstract":"<p><p>Despite a humidifier disinfectant (HD) product containing chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) with approximately 22% magnesium nitrate as a stabilizer, no report on the effects of magnesium nitrate on the respiratory toxicity of CMIT/MIT is available. In this study, Kathon CG and Proclin 200, containing approximately 1.5% CMIT/MIT with different magnesium nitrate concentrations (22.6% and 3%, respectively), were used to compare respiratory effects after intratracheal instillation (ITI) in C57BL/6 mice. C57BL/6 mice were randomized into groups of saline control, magnesium nitrate, Kathon CG, and Proclin 200 with 1.14 mg/kg of CMIT/MIT as the active ingredient, and administration was performed 6 times in a 2-3 day-interval in 2 weeks in all groups. Differential cell count analysis, cytokine analysis, and histological analysis of lung tissue were performed to characterize the injury features. Both Kathon and Proclin 200 induced an increase in inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid, in particular, eosinophils and type 2 T helper cell (Th2)-secreted cytokines. All histopathological changes including granulomatous inflammation, mixed inflammatory cell infiltration, mucous cell hyperplasia, eosinophil infiltration, and pulmonary fibrosis were induced with similar frequency and severity in Kathon CG and Proclin 200 groups. Our results suggested that magnesium nitrate did not affect CMIT/MIT-induced lung injury in the intratracheally instilled model. Further inhalation studies are needed to determine the distribution and toxicity differences of CMIT/MIT in the lungs according to the magnesium nitrate concentration.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"373-382"},"PeriodicalIF":2.3,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743940","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":"Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of <i>Locusta</i> <i>migratoria</i> (Orthoptera: Acrididae) as a novel food source.","authors":"Sun Young Kim, Kyu-Won Kwak, Ji Yeong Park, Eun-Sung Park, Chun-Ja Nam, Kyu Sup An, Hyun-Jin Kim, Hyung Joo Yoon, Yong-Soon Kim, Kwanho Park, Eunsun Kim, Hyeon Yeol Ryu, Sun-Don Kim","doi":"10.1007/s43188-023-00171-7","DOIUrl":"10.1007/s43188-023-00171-7","url":null,"abstract":"<p><p>The migratory locust, <i>Locusta</i> <i>migratoria</i> (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of <i>L.</i> <i>migratoria</i> had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of <i>L.</i> <i>migratoria</i> (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000 mg/kg/day. No toxicological changes were observed in both sexes of rats for 13 weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000 mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"317-331"},"PeriodicalIF":2.3,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247910","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":"Metabolic effects of diclofenac on the aquatic food chain - ¹ H-NMR study of water flea-zebrafish system.","authors":"Youzhen Li, Seonghye Kim, Sujin Lee, Suhkmann Kim","doi":"10.1007/s43188-022-00167-9","DOIUrl":"10.1007/s43188-022-00167-9","url":null,"abstract":"<p><p>In the environment, aquatic organisms are not only directly exposed to pollutants, but the effects can be exacerbated along the food chain. In this study, we investigated the effect of the food (water flea) on the secondary consumer (zebrafish) with the exposure diclofenac (DCF) Both organisms were exposed to an environmentally relevant concentrations (15 µg/L) of diclofenac for five days, and zebrafish were fed exposed and non-exposed water fleas, respectively. Metabolites of the water fleas were directly analyzed using HRMAS NMR, and for zebrafish, polar metabolite were extracted and analyzed using liquid NMR. Metabolic profiling was performed and statistically significant metabolites which affected by DCF exposure were identified. There were more than 20 metabolites with variable importance (VIP) score greater than 1.0 in comparisons in fish groups, and identified metabolites differed depending on the effect of exposure and the effect of food. Specifically, exposure to DCF significantly increased alanine and decreased NAD + in zebrafish, which means energy demand was increased. Additionally, the effects of exposed food decreased in guanosine, a neuroprotective metabolite, which explained that the neurometabolic pathway was perturbated by the feeding of exposed food. Our results which short-term exposed primary consumers to pollutants indirectly affected the metabolism of secondary consumers suggest that the long-term exposure further study remains to be investigated.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"307-315"},"PeriodicalIF":2.3,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242845","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":"Machine-learning based prediction models for assessing skin irritation and corrosion potential of liquid chemicals using physicochemical properties by XGBoost.","authors":"Yeonsoo Kang, Myeong Gyu Kim, Kyung-Min Lim","doi":"10.1007/s43188-022-00168-8","DOIUrl":"10.1007/s43188-022-00168-8","url":null,"abstract":"<p><p>Skin irritation test is an essential part of the safety assessment of chemicals. Recently, computational models to predict the skin irritation draw attention as alternatives to animal testing. We developed prediction models on skin irritation/corrosion of liquid chemicals using machine learning algorithms, with 34 physicochemical descriptors calculated from the structure. The training and test dataset of 545 liquid chemicals with reliable in vivo skin hazard classifications based on UN Globally Harmonized System [category 1 (corrosive, Cat 1), 2 (irritant, Cat 2), 3 (mild irritant, Cat 3), and no category (nonirritant, NC)] were collected from public databases. After the curation of input data through removal and correlation analysis, every model was constructed to predict skin hazard classification for liquid chemicals with 22 physicochemical descriptors. Seven machine learning algorithms [Logistic regression, Naïve Bayes, k-nearest neighbor, Support vector machine, Random Forest, Extreme gradient boosting (XGB), and Neural net] were applied to ternary and binary classification of skin hazard. XGB model demonstrated the highest accuracy (0.73-0.81), sensitivity (0.71-0.92), and positive predictive value (0.65-0.81). The contribution of physicochemical descriptors to the classification was analyzed using Shapley Additive exPlanations plot to provide an insight into the skin irritation of chemicals.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00168-8.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"295-305"},"PeriodicalIF":2.3,"publicationDate":"2023-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596479","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 circPalm2 inhibits sepsis-induced acute lung injury by sponging miR-376b-3p and targeting MAP3K1.","authors":"Pengfei Gao, Wenying Duan, Huiyan Shi, Qingxiu Wang","doi":"10.1007/s43188-022-00169-7","DOIUrl":"10.1007/s43188-022-00169-7","url":null,"abstract":"<p><p>The apoptosis and inflammation of pulmonary epithelial cells are important pathogenic factors of sepsis-induced acute lung injury (ALI). Upregulation of circPalm2 (circ_0001212) expression levels has been previously detected in the lung tissue of ALI rats. Herein, the biological significance and detailed mechanism of circPalm2 in ALI pathogenesis were investigated. In vivo models of sepsis-induced ALI were established by treating C57BL/6 mice with cecal ligation and puncture (CLP) surgery. Murine pulmonary epithelial cells (MLE-12 cells) were stimulated with lipopolysaccharide (LPS) to establish in vitro septic ALI models. MLE-12 cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry analysis, respectively. The pathological alterations of the lung tissue were analysed based on hematoxylin-eosin (H&E) staining. Cell apoptosis in the lung tissue samples was examined by TUNEL staining assay. LPS administration suppressed the viability and accelerated the inflammation and apoptotic behaviours of MLE-12 cells. CircPalm2 displayed high expression in LPS-stimulated MLE-12 cells and possessed circular characteristics. The silencing of circPalm2 impeded apoptosis and inflammation in LPS-stimulated MLE-12 cells. Mechanistically, circPalm2 bound with miR-376b-3p, which targeted MAP3K1. In rescue assays, MAP3K1 enhancement reversed the repressive effects of circPalm2 depletion on LPS-triggered inflammatory injury and MLE-12 cell apoptosis. Furthermore, the lung tissue collected from CLP model mice displayed low miR-376b-3p expression and high levels of circPalm2 and MAP3K1. CircPalm2 positively regulated MAP3K1 expression by downregulating miR-376b-3p in murine lung tissues. Importantly, circPalm2 knockdown attenuated CLP-induced inflammation, apoptosis, and pathological alterations in lung tissues collected from mice. Silenced circPalm2 inhibits LPS-induced pulmonary epithelial cell dysfunction and mitigates abnormalities in lung tissues collected from CLP-stimulated mice via the miR-376b-3p/MAP3K1 axis in septic ALI.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00169-7.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"275-294"},"PeriodicalIF":2.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296621","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}