Human & experimental toxicology最新文献_第3页

Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose. 广泛的靶向定量脂质组学揭示了长期接触双酚 A 和果糖后脂肪组织的脂质重塑。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241232609

Yonghong Tang, Guifang Ou, Ouyan Rang, Xu Liu, Xiaocheng Liu, Xinru Qin, Guojuan Li, Qing Yang, Mu Wang

{"title":"Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose.","authors":"Yonghong Tang, Guifang Ou, Ouyan Rang, Xu Liu, Xiaocheng Liu, Xinru Qin, Guojuan Li, Qing Yang, Mu Wang","doi":"10.1177/09603271241232609","DOIUrl":"10.1177/09603271241232609","url":null,"abstract":"Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25 μg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis. YTHDF1介导的鞘氨醇激酶2上调可通过PI3K/AKT轴减轻布比卡因诱导的神经毒性。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271231218707

Ru Yuan, Chunxia Wu

{"title":"YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis.","authors":"Ru Yuan, Chunxia Wu","doi":"10.1177/09603271231218707","DOIUrl":"10.1177/09603271231218707","url":null,"abstract":"Background: Bupivacaine (BUP), a long-acting local anesthetic, has been widely used in analgesia and anesthesia. However, evidence strongly suggests that excessive application of BUP may lead to neurotoxicity in neurons. Sphingosine kinase 2 (SPHK2) has been reported to exert neuroprotective effects. In this study, we intended to investigate the potential role and mechanism of SPHK2 in BUP-induced neurotoxicity in dorsal root ganglion (DRG) neurons.Methods: DRG neurons were cultured with BUP to simulate BUP-induced neurotoxicity in vitro. CCK-8, LDH, and flow cytometry assays were performed to detect the viability, LDH activity, and apoptosis of DRG neurons. RT-qPCR and western blotting was applied to measure gene and protein expression. Levels. MeRIP-qPCR was applied for quantification of m6A modification. RIP-qPCR was used to analyze the interaction between SPHK2 and YTHDF1.Results: SPHK2 expression significantly declined in DRG neurons upon exposure to BUP. BUP challenge substantially reduced the cell viability and increased the apoptosis rate in DRG neurons, which was partly abolished by SPHK2 upregulation. YTHDF1, an N6-methyladenosine (m6A) reader, promoted SPHK2 expression in BUP-treated DRG neurons in an m6A-dependent manner. YTHDF1 knockdown partly eliminated the increase in SPHK2 protein level and the protection against BUP-triggered neurotoxicity in DRG neurons mediated by SPHK2 overexpression. Moreover, SPHK2 activated the PI3K/AKT signaling to protect against BUP-induced cytotoxic effects on DRG neurons.Conclusions: In sum, YTHDF1-mediated SPHK2 upregulation ameliorated BUP-induced neurotoxicity in DRG neurons via promoting activation of the PI3K/AKT signaling pathway.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone. 比较同时暴露于可卡因和乙醇与单独暴露于可卡因的急性毒性。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241269024

Kwun Lok Cheung, Rex Pui Kin Lam, Chi Keung Chan, Man Li Tse, Matthew Sik Hon Tsui, Timothy Hudson Rainer

{"title":"Comparing the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone.","authors":"Kwun Lok Cheung, Rex Pui Kin Lam, Chi Keung Chan, Man Li Tse, Matthew Sik Hon Tsui, Timothy Hudson Rainer","doi":"10.1177/09603271241269024","DOIUrl":"https://doi.org/10.1177/09603271241269024","url":null,"abstract":"Introduction: Cocaine is commonly consumed with ethanol, which leads to the formation of cocaethylene through transesterification. Cocaethylene is an active metabolite of cocaine with a longer duration of action. Literature on the combined toxicity of cocaine, ethanol, and cocaethylene is conflicting. We aimed to compare the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone in Hong Kong.Methods: This was a retrospective study on acute cocaine toxicities reported to the Hong Kong Poison Control Center from 1 January 2010 to 22 January 2023. Cocaine exposure was confirmed by urine immunoassays/laboratory tests and ethanol co-ingestion was confirmed by blood ethanol concentrations. A serious outcome was defined as a National Poison Data System outcome moderate or above. Univariate analyses and multivariable logistic regression were performed to compare the associations of clinical outcomes with and without ethanol, followed by subgroup analyses of cases with complete data.Results: We analyzed 109 patients (median age 29 years, 71% men, 68% Chinese), of whom 20 had confirmed ethanol co-ingestion (mean blood ethanol concentration 1350 mg/L). Multivariable analysis showed that co-exposure to cocaine and ethanol was associated with a lower risk of serious outcomes (adjusted odds ratio 0.09, 95% confidence interval 0.01-0.77; p = 0.03) after adjusting for age, sex, ethnicity, route of cocaine administration, and physical health status. Subgroup analyses showed similar findings.Conclusions: In contrast to previous studies, we did not identify a higher risk of serious outcomes after co-exposure to cocaine and ethanol compared to cocaine alone in a predominantly Chinese cohort.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways. 砷诱导的 BRWD3 下调可通过 p53 和 p65 途径抑制肺腺癌细胞的增殖并诱导其凋亡。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241279166

Yanhua Zhu, Mei Xiao, Ruihuan Zhao, Xuefei Yang, Kun Wu, Xiao Liu, Xi Chen, Lei Guo, Jiezhen Liu, Xu Chen, Na Liu, Yuefeng He, Yanliang Zhang

{"title":"Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways.","authors":"Yanhua Zhu, Mei Xiao, Ruihuan Zhao, Xuefei Yang, Kun Wu, Xiao Liu, Xi Chen, Lei Guo, Jiezhen Liu, Xu Chen, Na Liu, Yuefeng He, Yanliang Zhang","doi":"10.1177/09603271241279166","DOIUrl":"10.1177/09603271241279166","url":null,"abstract":"Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including IκBα, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of antioxidant properties and cytotoxicity of brown algae (nizamuddinia zanardinii) in uterine (hela) and pancreatic cancer cell lines (paca-2). 评估褐藻（nizamuddinia zanardinii）在子宫癌细胞系（hela）和胰腺癌细胞系（paca-2）中的抗氧化特性和细胞毒性。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241227228

Milad Amerifar, Hesamoddin Arabnozari, Mohammad Shokrzadeh, Emran Habibi

{"title":"Evaluation of antioxidant properties and cytotoxicity of brown algae (nizamuddinia zanardinii) in uterine (hela) and pancreatic cancer cell lines (paca-2).","authors":"Milad Amerifar, Hesamoddin Arabnozari, Mohammad Shokrzadeh, Emran Habibi","doi":"10.1177/09603271241227228","DOIUrl":"10.1177/09603271241227228","url":null,"abstract":"Introduction: Pancreatic cancer and cervical cancer are among the most common cancers. Brown algae have anti-inflammatory, anti-cancer, anti-fungal, antioxidant, and immune-boosting properties. This study investigated the antioxidant properties and the effect of brown algae extract on pancreatic and uterine cancer cells.Materials and methods: In this study, Cervical (Hela) and pancreas (Paca-2) cancer cell lines were examined. The algae materials were extracted by sequential maceration method and amount of fucoxanthin content in the sample was determined by using High Performance Liquid Chromatography (HPLC) system. The cytotoxic effect of different concentrations of brown algae was measured by the MTT assay. All statistical calculations for comparing IC50 were analyzed using Graph Pad Prism software.Results: the algal sample contained an average of 102.52 ± 0.12 μg of fucoxanthin per 100 g. IC50 for 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide free radical scavenging activity for methanolic extract was 2.02 and 11.98 ± 0.13 respectively. Brown algae in all fractions inhibited cell growth and survival. In Hela cell lines, the methanolic extract was the most effective inhibitor, while in Paca cell lines, hexane and methanolic extracts were particularly potent. The methanolic extract was more toxic than other fractions on Hela and Paca cell lines.Conclusion: This study highlights brown algae extracts strong anticancer effects on uterine and pancreatic cancer cells, suggesting its potential as a natural anticancer drug. Different fractions of the extract showed superior apoptotic and cytotoxic effects, with higher concentrations leading to increased apoptotic effects and reduced survival rates of cancer cells.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction notice: "3,4-Methylenedioxymethamphetamine causes retinal damage in C57BL/6J mice". 撤稿通知："3,4-亚甲二氧基甲基苯丙胺导致 C57BL/6J 小鼠视网膜损伤》。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241262092

引用次数: 0

Protective effects of atractylenolide III on oxygen-glucose-deprivation/reperfusion-induced injury in HT22 cells. 白术内酯 III 对缺氧-葡萄糖/再灌注诱导的 HT22 细胞损伤的保护作用

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241288508

Roujia Guo, Siqi Quan, Yuan Liu, Jiahui Wang, Ziyang Huang, Xiuhui Guo, Ming Bai, Erping Xu, Xiangli Yan, Yucheng Li

{"title":"Protective effects of atractylenolide III on oxygen-glucose-deprivation/reperfusion-induced injury in HT22 cells.","authors":"Roujia Guo, Siqi Quan, Yuan Liu, Jiahui Wang, Ziyang Huang, Xiuhui Guo, Ming Bai, Erping Xu, Xiangli Yan, Yucheng Li","doi":"10.1177/09603271241288508","DOIUrl":"https://doi.org/10.1177/09603271241288508","url":null,"abstract":"Background: Atractylenolide III (ATL III) is a natural bioactive compound, that possesses anti-inflammatory, antioxidant, and neuroprotective properties. However, whether ATL III can protect against neuronal injury induced by cerebral ischemia/reperfusion (I/R) have not yet been studied. This study aimed to investigate the protective effects of ATL III on neuronal injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model in HT22 cells.Methods: Establishment of OGD/R model to induce HT22 cell injury in vitro. Cell viability, live-dead cell staining, oxidative stress levels, and pro-inflammatory cytokine levels were detected using kits. Cell apoptosis was observed by flow cytometry, and the expression of Bax, Bcl-2, and Caspase-3 proteins was detected by western blot.Results: ATL III significantly alleviates OGD/R-induced cell injury, as evidenced by the increased cell viability and reduced apoptosis rate. ATL III increased the levels of superoxide dismutase (SOD) and glutathione (GSH), while reducing malondialdehyde (MDA), reactive oxygen species (ROS), and the levels of TNF-α, IL-1β, and IL-6. The protein expression of Bax and Caspase-3 was downregulated, while Bcl-2 expression was upregulated by ATL III.Conclusion: ATL III as a potential therapeutic agent for reducing neuronal injury by mitigating oxidative stress, apoptosis, and inflammation.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The autocrine action of salidroside on osteoclast during osteoclastogenesis via hypoxia-inducible factor-1α pathway. 在破骨细胞生成过程中，水杨甙通过缺氧诱导因子-1α途径对破骨细胞产生自分泌作用。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241269028

Yutong Jin, Zhengyang Li, Lin Qi, Lingling Zhang, Dandan Gao, Haizhao Liu, Qingwen Cao, Chenchen Tian, Qun Xia, Yue Wang

{"title":"The autocrine action of salidroside on osteoclast during osteoclastogenesis via hypoxia-inducible factor-1α pathway.","authors":"Yutong Jin, Zhengyang Li, Lin Qi, Lingling Zhang, Dandan Gao, Haizhao Liu, Qingwen Cao, Chenchen Tian, Qun Xia, Yue Wang","doi":"10.1177/09603271241269028","DOIUrl":"10.1177/09603271241269028","url":null,"abstract":"Background and objective: The objective of this study was to investigate the potential of salidroside (SAL) (a major active compound in Rhodiola rosea L.) in regulating osteoclast differentiation and function by modulating the HIF-1α pathway and its downstream target genes.Methods: The expression of HIF-1α and its downstream target genes was examined at both mRNA and protein levels in osteoclasts treated with SAL. Immunofluorescence analysis was performed to assess the nuclear translocation and transcriptional activity of HIF-1α in response to SAL. MTT, flow cytometry, qPCR, TRAP staining and bone resorption assays were used to evaluate the potential effect of salidroside on osteoclasts.Results: SAL enhanced the expression of HIF-1α and its downstream target genes in osteoclasts. Immunofluorescence analysis confirmed the facilitation of HIF-1α nuclear translocation and transcriptional activity by SAL. In addition, SAL enhanced osteoclast viability, differentiation and bone resorption activity in an autocrine manner through HIF-1α/VEGF, IL-6 and ANGPTL4 pathways.Conclusion: SAL promotes osteoclast proliferation, differentiation and bone resorption through HIF-1α/VEGF, IL-6 and ANGPTL4 pathways.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of doxorubicin on autophagy in fibroblasts. 多柔比星对成纤维细胞自噬的影响

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241231947

Anna Shuey, Conner Patricelli, Julia T Oxford, Xinzhu Pu

{"title":"Effects of doxorubicin on autophagy in fibroblasts.","authors":"Anna Shuey, Conner Patricelli, Julia T Oxford, Xinzhu Pu","doi":"10.1177/09603271241231947","DOIUrl":"10.1177/09603271241231947","url":null,"abstract":"Objectives: Doxorubicin (DOX) is a highly effective chemotherapeutic used to treat many adult and pediatric cancers, such as solid tumors, leukemia, lymphomas and breast cancer. It can also cause injuries to multiple organs, including the heart, liver, and brain or kidney, although cardiotoxicity is the most prominent side effect of DOX. In this study, we examined the potential effects of DOX on autophagy activity in two different mouse fibroblasts.Methods: Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX to assess changes in the expression of two commonly used autophagy protein markers, LC3II and p62. We also examined the effects of DOX the on expression of key genes that encode components of the molecular machinery and regulators modulating autophagy in response to both extracellular and intracellular signals.Results: We observed that LC3II levels increased and p62 levels decreased following the DOX treatment in NIH3T3 cells. However, similar effects were not observed in primary cardiac fibroblasts. In addition, DOX treatment induced the upregulation of a significant number of genes involved in autophagy in NIH3T3 cells, but not in primary cardiac fibroblasts.Conclusions: Taken together, these results indicate that DOX upregulates autophagy in fibroblasts in a cell-specific manner.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of miR-138-5p alleviates propofol-induced neurotoxicity and autophagy by regulating SIRT1. 下调 miR-138-5p 可通过调节 SIRT1 减轻异丙酚诱导的神经毒性和自噬。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241269021

Xiaolong Zhang, Yiqiao Wang, Feng Xu, Binbin Zhao, Xiangnan Liang, Jianwei Shu

{"title":"Downregulation of miR-138-5p alleviates propofol-induced neurotoxicity and autophagy by regulating SIRT1.","authors":"Xiaolong Zhang, Yiqiao Wang, Feng Xu, Binbin Zhao, Xiangnan Liang, Jianwei Shu","doi":"10.1177/09603271241269021","DOIUrl":"10.1177/09603271241269021","url":null,"abstract":"Background: Propofol, a commonly utilized anesthetic, has been shown to induce neurotoxicity in developing neurons. A previous study showed that microRNA (miR)-138-5p was dysregulated in hippocampus tissue of mice administrated with propofol. The current study aimed to investigate the functions of miR-138-5p and its target gene in propofol-induced neurotoxicity.Methods: SH-SY5Y neuronal cells were treated with increasing doses of propofol for indicated time to identify the optimal concentration and treatment time. MiR-138-5p and SIRT1 expression in SH-SY5Y neuronal cells stimulated with propofol were measured by RT-qPCR. Western blotting was performed to quantify protein levels of SIRT1 and autophagy markers. After interference of miR-138-5p and/or SIRT1 expression, the toxicity of SH-SY5Y neuronal cells was evaluated by cell counting kit-8 (CCK-8) assays and flow cytometry. The formation of autophagosomes was estimated by monodansylcadaverine staining.Results: Propofol induced neurotoxicity in a dose- or time-dependent manner. Propofol upregulated miR-138-5p while downregulating SIRT1 in SH-SY5Y neuronal cells. The propofol-stimulated neurotoxicity and autophagy was inhibited by miR-138-5p knockdown. Moreover, miR-138-5p bound to SIRT1 3'untranslated region. SIRT1 overexpression increased cell viability while inhibiting apoptosis and autophagy in the context of propofol. SIRT1 downregulation reversed the ameliorative effect of miR-138-5p inhibition on propofol-induced neurotoxicity and autophagy.Conclusion: Downregulation of miR-138-5p alleviates propofol-induced neurotoxicity and autophagy via upregulation of SIRT1.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0