Human & Experimental Toxicology最新文献_第8页

Tanshinone IIA inhibits ischemia-reperfusion-induced inflammation, ferroptosis and apoptosis through activation of the PI3K/Akt/mTOR pathway. 丹参酮IIA通过激活PI3K/Akt/mTOR通路抑制缺血再灌注诱导的炎症、铁下垂和细胞凋亡。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231180864

Rui Zhang, Yunen Liu, Jihui You, Baiping Ge

{"title":"Tanshinone IIA inhibits ischemia-reperfusion-induced inflammation, ferroptosis and apoptosis through activation of the PI3K/Akt/mTOR pathway.","authors":"Rui Zhang, Yunen Liu, Jihui You, Baiping Ge","doi":"10.1177/09603271231180864","DOIUrl":"https://doi.org/10.1177/09603271231180864","url":null,"abstract":"Ischemia-reperfusion (I/R) is a common clinical process, and the lung is one of the most sensitive organs of I/R injury, which often leads to acute lung injury (ALI). Tanshinone IIA (Tan IIA) has anti-inflammatory, antioxidant, and anti-apoptotic activities. However, the effects of Tan IIA on lung I/R injury remain uncertain. Twenty-five C57BL/6 mice were randomly divided into five groups: control (Ctrl), I/R, I/R + Tan IIA, I/R + LY294002 and I/R + Tan IIA + LY294002 group. Tan IIA (30 μg/kg) was injected intraperitoneally 1 h before injury in the I/R + Tan IIA and I/R + Tan IIA + LY294002 groups. These data showed that Tan IIA significantly improved I/R-induced histological changes and scores of lung injury, decreased lung W/D ratio, MPO and MDA contents, reduced infiltration of inflammatory cells, and decreased the expression of IL-1β, IL-6 and TNF-α. Meanwhile, Tan IIA significantly increased the expression of Gpx4 and SLC7A11, and decreased the expression of Ptgs2 and MDA. Moreover, Tan IIA significantly reversed the low expression of Bcl2, and the high expression of Bax, Bim, Bad and cleave-caspase 3. Furthermore, Tan IIA caused a significant increase in the phosphorylation levels of PI3K, Akt and mTOR in the lungs. However, these beneficial effects of Tan IIA on I/R-induced lung inflammation, ferroptosis and apoptosis were offset by LY294002. Our data suggest that Tan IIA significantly ameliorates I/R-induced ALI, which is mediated through activation of PI3K/Akt/mTOR pathway.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231180864"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9639412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Silencing lncRNA HCG18 regulates GPX4-inhibited ferroptosis by adsorbing miR-450b-5p to avert sorafenib resistance in hepatocellular carcinoma. 沉默lncRNA HCG18通过吸附miR-450b-5p来调节gpx4抑制的铁凋亡，从而避免肝癌中索拉非尼的耐药。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271221142818

Xiaoming Li, Yunhui Li, Peilong Lian, Qigang Lv, Fangfeng Liu

{"title":"Silencing lncRNA HCG18 regulates GPX4-inhibited ferroptosis by adsorbing miR-450b-5p to avert sorafenib resistance in hepatocellular carcinoma.","authors":"Xiaoming Li, Yunhui Li, Peilong Lian, Qigang Lv, Fangfeng Liu","doi":"10.1177/09603271221142818","DOIUrl":"https://doi.org/10.1177/09603271221142818","url":null,"abstract":"Ferroptosis is potential to relieve drug resistance in hepatocellular carcinoma (HCC). Glutathione peroxidase 4 (GPX4) is a critical modulator of ferroptosis. This study discussed the mechanism of GPX4-inhibited ferroptosis in sorafenib resistance in HCC. HCG18 in HCC cells was detected. Sorafenib resistant (SR) cell line Huh7-SR cells were treated with sorafenib (0, 2.5, 5, 7.5, 10 μM). After silencing HCG18 in Huh7-SR cells, cell activity, proliferation and apoptosis were detected. The levels of iron, the concentration of MDA, GSH and lipid reactive oxygen species (ROS) were measured to evaluate the ferroptosis. The downstream mechanism of HCG18 was predicted and verified. Huh7-SR cells were infected with lentivirus sh-HCG18 to establish xenograft tumor model. HCG18 was elevated in HCC cells and associated with sorafenib resistance. Silencing HCG18 inhibited cell proliferation, promoted apoptosis, and impaired sorafenib resistance. Ferroptosis was inhibited in Huh7-SR cells, while silencing HCG18 inhibited sorafenib resistance by promoting ferroptosis. GPX4 overexpression averted the promotion of sh-HCG18 on ferroptosis, thereby reducing sorafenib resistance. HCG18 sponged miR-450b-5p to regulate GPX4. Collectively, Silencing HCG18 inhibits GPX4 by binding to miR-450b-5p, promotes GPX4-inhibited ferroptosis, and averts sorafenib resistance in HCC.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221142818"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10705543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Preclinical Evaluation of interferon-gamma primed human Wharton's jelly-derived mesenchymal stem cells. 干扰素γ引发的人类沃顿氏胶状间充质干细胞的临床前评估。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231171650

Sang-Jin Park, Dae Seong Kim, Myeongjin Choi, Kang-Hyun Han, Ji-Seok Han, Keon Hee Yoo, Kyoung-Sik Moon

{"title":"Preclinical Evaluation of interferon-gamma primed human Wharton's jelly-derived mesenchymal stem cells.","authors":"Sang-Jin Park, Dae Seong Kim, Myeongjin Choi, Kang-Hyun Han, Ji-Seok Han, Keon Hee Yoo, Kyoung-Sik Moon","doi":"10.1177/09603271231171650","DOIUrl":"https://doi.org/10.1177/09603271231171650","url":null,"abstract":"The potential of human mesenchymal stem cells (MSCs) for cell therapy has been investigated in numerous immune-mediated conditions; MSCs are considered one of the most promising cellular therapeutics to treat intractable diseases. Recently, approaches to prime MSCs have been investigated, thereby generating cellular products with enhanced potential for a variety of clinical applications. Interferon-gamma (IFN-γ) priming is a current approach used to increase the therapeutic efficacy of MSCs. In this study, we determined the systemic toxicity, tumorigenicity and biodistribution of IFN-γ-primed Wharton's jelly-derived (WJ)-MSCs in male and female BALB/c-nu/nu mice. There were no deaths or pathologic lesions in the mice treated with 5 × 106 cells/kg IFN-γ-primed MSCs in the repeated dose study. In the tumorigenicity study, one of the subcutaneously treated mice showed bronchioloalveolar adenoma in the lung but tested negative for human-specific anti-mitochondrial antibody, suggesting the spontaneous murine origin of the adenoma. A biodistribution study using real-time quantitative polymerase chain reaction demonstrated the systemic IFN-γ-primed MSC clearance by day 28. Based on the toxicity, biodistribution, and tumorigenicity studies, we concluded that IFN-γ-primed MSCs at 5 × 106 cells/kg do not induce tumor formation and adverse changes.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231171650"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9389222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats. TLR4/MyD88/NF-κB信号通路参与二cerein对大鼠肺纤维化的保护作用。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231200213

Asmaa Mohamed Abdel-Aziz, Eman Mahmoud Fathy, Heba M Hafez, Amira F Ahmed, Mervat Z Mohamed

{"title":"TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats.","authors":"Asmaa Mohamed Abdel-Aziz, Eman Mahmoud Fathy, Heba M Hafez, Amira F Ahmed, Mervat Z Mohamed","doi":"10.1177/09603271231200213","DOIUrl":"10.1177/09603271231200213","url":null,"abstract":"Purpose: Pulmonary fibrosis (PF) is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on PF injury has not yet been fully clarified. Therefore, the current study aimed to detect its protective effect on lung tissue with the explanation of possible underlying mechanisms.Methods: Adult male albino rats were assigned to four groups: control group, diacerein control group, PF non-treated group, and PF diacerein pretreated group. Lung tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and myeloid differentiation factor 88 (MyD88) levels were determined. Histopathological examination of lung tissue and immunohistochemical studies of nuclear factor-kappa B (NF-κB), and transforming growth factor- β (TGF-β) were also done.Results: Diacerein pretreatment has the ability to restore the PF damaging effect, proved by the reduction of the oxidative stress and lung tissue inflammation via downregulation of TLR4/NF-κB signaling pathway together with the restoration of TGF-β level and improvement of the histopathological and immunohistochemical study findings in the lung tissue.Conclusion: These results suggested the protective effect of diacerein on PF relies on its antioxidant and anti-inflammatory effects reducing TLR4/NF-κB signaling pathway.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231200213"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10147864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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. 撤回通知。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231192805

引用次数: 0

A review of challenges and prospects of 3D cell-based culture models used for studying drug induced liver injury during early phases of drug development. 在药物开发的早期阶段，用于研究药物性肝损伤的3D细胞培养模型的挑战和前景综述。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271221147884

John K Chipangura, Yonela Ntamo, Bert Mohr, Nireshni Chellan

{"title":"A review of challenges and prospects of 3D cell-based culture models used for studying drug induced liver injury during early phases of drug development.","authors":"John K Chipangura, Yonela Ntamo, Bert Mohr, Nireshni Chellan","doi":"10.1177/09603271221147884","DOIUrl":"https://doi.org/10.1177/09603271221147884","url":null,"abstract":"Drug-induced liver injury (DILI) is the leading cause of compound attrition during drug development. Over the years, a battery of in-vitro cell culture toxicity tests is being conducted to evaluate the toxicity of compounds prior to testing in laboratory animals. Two-dimensional (2D) in-vitro cell culture models are commonly used and have provided a great deal of knowledge; however, these models often fall short in mimicking natural structures of tissues in-vivo. Testing in humans is the most logical method, but unfortunately there are ethical limitations associated with human tests. To overcome these limitations better human-relevant, predictive models are required. The past decade has witnessed significant efforts towards the development of three-dimensional (3D) in-vitro cell culture models better mimicking in-vivo physiology. 3D cell culture has advantages in being representative of the interactions of cells in-vivo and when validated can act as an interphase between 2D cell culture models and in-vivo animal models. The current review seeks to provide an overview of the challenges that make biomarkers used for detection of DILI not to be sensitive enough during drug development and explore how 3D cell culture models can be used to address the gap with the current models.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221147884"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal cyanuric acid exposure induced spatial learning impairments associated with alteration of acetylcholine-mediated neural information flow at the hippocampal CA3-CA1 synapses of male rats. 产前三聚尿酸暴露诱导的空间学习障碍与乙酰胆碱介导的海马CA3-CA1突触神经信息流的改变有关。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231163477

Wei Sun, Xuanyin Zhao, Yiwen Wan, Yang Yang, Xiaoliang Li, Xiao Chen, Yazi Mei, Lei An

{"title":"Prenatal cyanuric acid exposure induced spatial learning impairments associated with alteration of acetylcholine-mediated neural information flow at the hippocampal CA3-CA1 synapses of male rats.","authors":"Wei Sun, Xuanyin Zhao, Yiwen Wan, Yang Yang, Xiaoliang Li, Xiao Chen, Yazi Mei, Lei An","doi":"10.1177/09603271231163477","DOIUrl":"https://doi.org/10.1177/09603271231163477","url":null,"abstract":"Cyanuric acid (CA) is reported to induce nephrotoxicity but its toxic effect is not fully known. Prenatal CA exposure causes neurodevelopmental deficits and abnormal behavior in spatial learning ability. Dysfunction of the acetyl-cholinergic system in neural information processing is correlated with spatial learning impairment and was found in the previous reports of CA structural analogue melamine. To further investigate the neurotoxic effects and the potential mechanism, the acetylcholine (ACh) level was detected in the rats which were exposed to CA during the whole of gestation. Local field potentials (LFPs) were recorded when rats infused with ACh or cholinergic receptor agonist into hippocampal CA3 or CA1 region were trained in the Y-maze task. We found the expression of ACh in the hippocampus was significantly reduced in dose-dependent manners. Intra-hippocampal infusion of ACh into the CA1 but not the CA3 region could effectively mitigate learning deficits induced by CA exposure. However, activation of cholinergic receptors did not rescue the learning impairments. In the LFP recording, we found that the hippocampal ACh infusions could enhance the values of phase synchronization between CA3 and CA1 regions in theta and alpha oscillations. Meanwhile, the reduction in the coupling directional index and the strength of CA3 driving CA1 in the CA-treated groups was also reversed by the ACh infusions. Our findings are consistent with the hypothesis and provide the first evidence that prenatal CA exposure induced spatial learning defect is attributed to the weakened ACh-mediated neuronal coupling and NIF in the CA3-CA1 pathway.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231163477"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9136776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Kaempferol ameliorates palmitate-induced lipid accumulation in HepG2 cells through activation of the Nrf2 signaling pathway. 山奈酚通过激活Nrf2信号通路改善棕榈酸盐诱导的HepG2细胞脂质积累。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271221146780

Li Zhao, Liping Yang, Khalidamir Ahmad

{"title":"Kaempferol ameliorates palmitate-induced lipid accumulation in HepG2 cells through activation of the Nrf2 signaling pathway.","authors":"Li Zhao, Liping Yang, Khalidamir Ahmad","doi":"10.1177/09603271221146780","DOIUrl":"https://doi.org/10.1177/09603271221146780","url":null,"abstract":"Objectives: Kaempferol (KMF), has beneficial effects against hepatic lipid accumulation. In this study, we aimed to investigate molecular mechanism underlying the protective effect of KMF on lipid accumulation.Methods: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24 h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.Results: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).Conclusion: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221146780"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Hyperoside exerts protective effects against anticardiolipin antibody-induced recurrent pregnancy loss in vivo and in vitro. 金丝桃苷在体内和体外对抗心磷脂抗体诱导的复发性妊娠丢失具有保护作用。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231163476

Yanli Song, Dongjie He, Shaoqi Shi, Tianwei Cui, Hui Zhang, Xianmin Zhao, Tingting Ni, Huidongzi Xiao, Aiwu Wei

{"title":"Hyperoside exerts protective effects against anticardiolipin antibody-induced recurrent pregnancy loss in vivo and in vitro.","authors":"Yanli Song, Dongjie He, Shaoqi Shi, Tianwei Cui, Hui Zhang, Xianmin Zhao, Tingting Ni, Huidongzi Xiao, Aiwu Wei","doi":"10.1177/09603271231163476","DOIUrl":"https://doi.org/10.1177/09603271231163476","url":null,"abstract":"Background: Women with antiphospholipid syndrome (APS) or antiphospholipid antibodies (aPLs) are at high risk for obstetric complications, including recurrent pregnancy loss (RPL). However, effective treatments for RPL are lacking.Objective: This study aimed to reveal the function and underlying mechanism of hyperoside (Hyp) in RPL associated with antiphospholipid antibodies (aCLs).Methods: The pregnant rats (N = 24) were divided randomly into four groups: normal human-IgG (NH-IgG); aCL-pregnancy loss (aCL-PL); aCL-PL + Hyp (40 mg/kg/day); aCL-PL + low molecular weight heparin (LMWH, 525 μg/kg/day). HTR-8 cells were treated with 80 μg/mL aCL to establish the cell models of miscarriage.Results: In pregnant rats, aCL-IgG injection raised the abortion rate of embryos, while Hyp treatment inhibited the effects. Additionally, Hyp inhibited the platelet activation and uteroplacental insufficiency caused by aCL. In vivo and in vitro experiments further suggested that Hyp suppressed aCL-induced inflammation and apoptosis by downregulating NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-related factors and decreasing apoptotic rates. After aCL administration, Hyp therapy downregulated the expression of purinergic ligand-gated ion channel 7 (P2X7), which is reported to induce cytokine release and apoptosis. Furthermore, we found that the treatment of 3'-O-(4-Benzoyl) benzoyl-ATP (BzATP, an agonist of the P2X7 receptor) reversed the inhibitory effects of Hyp on cell function.Conclusions: Hyp exerts protective effects on aCL-induced pregnancy loss by preventing platelet activation-mediated P2X7/NLRP3 pathway. Therefore, Hyp may provide a feasible pharmaceutical strategy for the treatment of RPL.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231163476"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9644157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alpha-lipoic acid inhibits sodium arsenite-mediated autophagic death of rat insulinoma cells. 硫辛酸抑制亚砷酸钠介导的大鼠胰岛素瘤细胞自噬死亡。

IF 2.8 4区医学

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271221149196

Yong Cheng, Xiuli Yang, Wenjuan Tang, Qiong Fu, Hong Li, Bing Liang

{"title":"Alpha-lipoic acid inhibits sodium arsenite-mediated autophagic death of rat insulinoma cells.","authors":"Yong Cheng, Xiuli Yang, Wenjuan Tang, Qiong Fu, Hong Li, Bing Liang","doi":"10.1177/09603271221149196","DOIUrl":"https://doi.org/10.1177/09603271221149196","url":null,"abstract":"Aim: To investigate the protective effect of α-lipoic acid on sodium arsenite (NaAsO2) induced INS-1 cells injury and its mechanism.Methods: The cell viability was measured by CCK-8 assay. The autophagosomes was observed under transmission electron microscopy. The autophagosomes in cells transfected with green fluorescent protein microtubule-associated protein light chain 3 (GFP-LC3) plasmids were observed under a laser scanning con-focal microscope. The expression of LC3-II, P62, PI3K, and mTOR proteins in INS-1 cells treated with a combination of chloroquine (CQ, autophagy inhibitor) and NaAsO2 were detected by Western blot assay. The expression of LC3-II, P62, PI3K, and mTOR proteins were detected in INS-1 cells treated with a combination of rapamycin (autophagy inducer, mTOR inhibitor) and α-LA.Results: The cytotoxicity induced by NaAsO2 was reversed by α-LA, and the viability of NaAsO2-treated INS-1 cells increased. α-LA pretreatment decreased the autophagosome accumulation induced by NaAsO2. α-LA also reduced the fluorescence spot aggregation of GFP-LC3 in INS-1 cells exposed to NaAsO2 as observed under a laser scanning con-focal microscope. α-LA inhibited NaAsO2 induced autophagy by up-regulating PI3K and mTOR and down-regulating LC3-II and P62. CQ inhibited NaAsO2 induced autophagy by up-regulating PI3K, mTOR, P62 and down-regulating LC3-II. α-LA inhibited rapamycin-induced autophagy by up-regulating PI3K, mTOR and P62 and down-regulating LC3-II. The results showed that NaAsO2 could induce autophagy activation in INS-1 cells. The α-LA may inhibit autophagy activation by regulating the PI3K/mTOR pathway.Conclusion: The data indicated that α-LA might inhibit the NaAsO2-induced autophagic death of INS-1 cells by regulating the PI3K/mTOR pathway.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221149196"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10479217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0