Human & experimental toxicology最新文献_第3页

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

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

Epidemiology studies on effects of lithium salts in pregnancy are confounded by the inability to control for other potentially teratogenic factors. 有关锂盐对妊娠影响的流行病学研究由于无法控制其他潜在致畸因素而受到干扰。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241236346

Carr J Smith, Victoria M Payne

{"title":"Epidemiology studies on effects of lithium salts in pregnancy are confounded by the inability to control for other potentially teratogenic factors.","authors":"Carr J Smith, Victoria M Payne","doi":"10.1177/09603271241236346","DOIUrl":"10.1177/09603271241236346","url":null,"abstract":"Introduction: In bipolar women who took lithium during pregnancy, several epidemiology studies have reported small increases in a rare fetal cardiac defect termed Ebstein's anomaly.Methods: Behavioral, environmental, and lifestyle-associated risk factors associated with bipolar disorder and health insurance status were determined from an Internet search. The search was conducted from October 1, 2023, through October 14, 2023. The search terms employed included the following: bipolar, bipolar disorder, mood disorders, pregnancy, congenital heart defects, Ebstein's anomaly, diabetes, hypertension, Medicaid, Medicaid patients, alcohol use, cigarette smoking, marijuana, cocaine, methamphetamine, narcotics, nutrition, diet, obesity, body mass index, environment, environmental exposures, poverty, socioeconomic status, divorce, unemployment, and income. No quotes, special fields, truncations, etc., were used in the searches. No filters of any kind were used in the searches.Results: Women who remain on lithium in the United States throughout their pregnancy are likely to be experiencing mania symptoms and/or suicidal ideation refractory to other drugs. Pregnant women administered the highest doses of lithium salts would be expected to have been insufficiently responsive to lower doses. Any small increases in the retrospectively determined risk of fetal cardiac anomalies in bipolar women taking lithium salts cannot be disentangled from potential developmental effects resulting from very high rates of cigarette smoking, poor diet, alcohol abuse, ingestion of illegal drugs like cocaine or opioids, marijuana smoking, obesity, and poverty.Conclusions: The small risks in fetal cardiac abnormalities reported in the epidemiology literature do not establish a causal association for lithium salts and Ebstein's anomaly.","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":"139941401","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

Acacetin inhibits activation of microglia to improve neuroinflammation after subarachnoid hemorrhage through the PERK signaling pathway mediated autophagy. 阿卡西汀通过 PERK 信号通路介导的自噬作用抑制小胶质细胞的激活，从而改善蛛网膜下腔出血后的神经炎症。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241251447

Ying Liu, Jianhua Tang, Yiwei Hou, Lu Li, Wenna Li, Ling Yu, Xue Wang, Changbai Sui

{"title":"Acacetin inhibits activation of microglia to improve neuroinflammation after subarachnoid hemorrhage through the PERK signaling pathway mediated autophagy.","authors":"Ying Liu, Jianhua Tang, Yiwei Hou, Lu Li, Wenna Li, Ling Yu, Xue Wang, Changbai Sui","doi":"10.1177/09603271241251447","DOIUrl":"10.1177/09603271241251447","url":null,"abstract":"Purpose: To explore the effect of acacetin on subarachnoid hemorrhage (SAH) and its possible mechanism.Methods: SAH model of rat was established, and intraperitoneally injected with three doses of acacetin. To verify the role of PERK pathway, we used the CCT020312 (PERK inhibitor) and Tunicamycin (activators of endoplasmic reticulum stress). The SAH score, neurological function score, brain edema content, and Evans blue (EB) exudate were evaluated. Western blot was used to determine the expression of inflammation-associated proteins and PERK pathway. The activation of microglia was also determined through Iba-1 detection. TEM and immunofluorescence staining of LC3B were performed to observe the autophagy degree of SAH rats after acacetin. Tunel/NeuN staining, HE and Nissl' staining were performed for neuronal damage.Results: Acacetin increased the neurological function score, reduce brain water content, Evans blue exudation and SAH scores. The microglia in cerebral cortex were activated after SAH, while acacetin could inhibit its activation, and decreased the expression of TNF-α and IL-6 proteins. The pathological staining showed the severe neuronal damage and increased neuronal apoptosis after SAH, while acacetin could improve these pathological changes. We also visualized the alleviated autophagy after acacetin. The expression of Beclin1 and ATF4 proteins were increased, but acacetin could inhibit them. Acacetin also inactivated PERK pathway, which could improve the neuronal injury and neuroinflammation after SAH, inhibit the microglia activation and the overactivated autophagy through PERK pathway.Conclusion: Acacetin may alleviate neuroinflammation and neuronal damage through PERK pathway, thus having the protective effect on EBI after SAH.","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":"140893063","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

Stereotactic body radiation therapy suppresses myeloid-derived suppressor cells by regulating miR-21/Sorbin and SH3 Domain-containing Protein 1 axis. 立体定向体放射治疗通过调节 miR-21/Sorbin 和含 SH3 域蛋白 1 轴抑制髓源性抑制细胞。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241261307

ChunFang Zhao, Qi Tang, Congbo Yang, Lingli Zhou, Jinli Peng, Tianwen Zhang, Shaoqiang Zhou, Ya Li

{"title":"Stereotactic body radiation therapy suppresses myeloid-derived suppressor cells by regulating miR-21/Sorbin and SH3 Domain-containing Protein 1 axis.","authors":"ChunFang Zhao, Qi Tang, Congbo Yang, Lingli Zhou, Jinli Peng, Tianwen Zhang, Shaoqiang Zhou, Ya Li","doi":"10.1177/09603271241261307","DOIUrl":"10.1177/09603271241261307","url":null,"abstract":"Background: Stereotactic body radiation therapy (SBRT) is a targeted form of radiotherapy used to treat early-stage cancers. Despite its effectiveness, the impact of SBRT on myeloid-derived suppressor cells (MDSCs) is not well understood. In this study, we examined how SBRT affects the differentiation and survival of MDSCs, as well as delved into the molecular mechanisms involved.Methods and results: SBRT was utilized on bone marrow (BM)-derived MDSCs to investigate its impact on the differentiation and survival of MDSCs using flow cytometry. An animal model of lung cancer was created to assess the anti-cancer properties of SBRT and the role of miR-21 expression in MDSCs. The interplay of miR-21 and Sorbin and SH3 domain-containing protein 1 (SORBS1) in MDSC differentiation was explored through dual luciferase activity assay, RT-qPCR, and Western blot analysis. The findings suggest that SBRT led to an increase in miR-21 levels, inhibited MDSC differentiation, and triggered cell apoptosis in BM cells. Inhibition of miR-21 reversed the effects of SBRT on MDSC differentiation and apoptosis. Additionally, it was revealed that SORBS1 was a downstream target of miR-21 in BM cells, and the miR-21/SORBS1 axis played a role in regulating MDSC differentiation and apoptosis induced by SBRT. Modulating miR-21 levels in vivo impinged on the response to SBRT treatment and the quantity of MDSCs in a mouse model of lung cancer.Conclusion: Our data indicate that the upregulation of miR-21 induced by SBRT may contribute to the inhibition of MDSC expansion in a lung cancer model.","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":"141319303","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":"https://doi.org/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

Evaluation of Cd-induced cytotoxicity in primary human keratinocytes. 评估 Cd 诱导的原代人类角质细胞细胞毒性。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271231224458

Daniil Romashin, Viktoriia Arzumanian, Ekaterina Poverennaya, Alexandra Varshaver, Nataliya Luzgina, Alexander Rusanov

{"title":"Evaluation of Cd-induced cytotoxicity in primary human keratinocytes.","authors":"Daniil Romashin, Viktoriia Arzumanian, Ekaterina Poverennaya, Alexandra Varshaver, Nataliya Luzgina, Alexander Rusanov","doi":"10.1177/09603271231224458","DOIUrl":"10.1177/09603271231224458","url":null,"abstract":"An increasing number of studies have investigated the effects of Cd on human health. Cd-induced dermatotoxicity is an important field of research, but numerous studies have focused on the effects of Cd on the human skin. Moreover, most studies have been performed using HaCaT cells but not primary keratinocytes. In this study, we provide the results describing the cytotoxic effects of Cd exposure on primary human epidermal keratinocytes obtained from different donors. The subtoxic concentration of cadmium chloride was determined via MTT assay, and transcriptomic analysis of the cells exposed to this concentration (25 µM) was performed. As in HaCaT cells, Cd exposure resulted in increased ROS levels, cell cycle arrest, and induction of apoptosis. In addition, we report that exposure to Cd affects zinc and copper homeostasis, induces metallothionein expression, and activates various signaling pathways, including Nrf2, NF-kB, TRAIL, and PI3K. Cd induces the secretion of various cytokines (IL-1, IL-6, IL-10, and PGE2) and upregulates the expression of several cytokeratins, such as KRT6B, KRT6C, KRT16, and KRT17. The results provide a better understanding of the mechanisms of cadmium-induced cytotoxicity and its effect on human epidermal skin 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":"139089739","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 mixtures of flavor chemicals in a 90-day nose-only exposures in sprague-dawley rats. 在斯普拉格-道利大鼠的 90 天鼻接触中评估香料化学品混合物。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241269022

Michael J Oldham, Rahat Wadhwa Desai, James Randazzo, Brent E Walling, Guy Lalonde, Roxana Weil

{"title":"Evaluation of mixtures of flavor chemicals in a 90-day nose-only exposures in sprague-dawley rats.","authors":"Michael J Oldham, Rahat Wadhwa Desai, James Randazzo, Brent E Walling, Guy Lalonde, Roxana Weil","doi":"10.1177/09603271241269022","DOIUrl":"https://doi.org/10.1177/09603271241269022","url":null,"abstract":"Background: One of the challenges to using some flavor chemicals in aerosol products is the lack of route of administration specific toxicology data.Methods: Flavor chemicals (88) were divided into four different flavor mixtures based upon chemical compatibility and evaluated in 2-week dose-range-finding and subsequent 90-day nose-only rodent inhalation studies (OECD 413 and GLP compliant). Sprague-Dawley rats were exposed to vehicle control or one of three increasing concentrations of each flavor mixture.Results: In the dose-range-range-finding studies, exposure to flavor mixture four resulted in adverse nasal histopathology in female rats at the high dose, resulting in this flavor mixture not being evaluated in a 90-day study. In the 90-day studies daily exposures to the three flavor mixtures did not induce biologically meaningful adverse effects (food consumption, body weights, respiratory physiology, serum chemistry, hematology, coagulation, urinalysis, bronchoalveolar lavage fluid analysis and terminal organ weights). All histopathology findings were observed in both vehicle control and flavor mixture exposed animals, with similar incidences and/or severities, and therefore were not considered flavor mixture related.Conclusion: Based on the absence of adverse effects, the no-observed-adverse-effect concentration for each 90-day inhalation study was the highest dose tested, 2.5 mg/L of the aerosolized high dose of the three flavor mixtures.","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":"141891371","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 effects of Wharton's jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice. 沃顿果冻间充质干细胞分泌物对恢复硫胺素诱导的雄性小鼠生殖毒性的影响

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241269019

Sedigheh Bahmyari, Sanaz Alaee, Zahra Khodabandeh, Tahereh Talaei-Khozani, Mahintaj Dara, Shayesteh Mehdinejadiani, Arezoo Solati

{"title":"The effects of Wharton's jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice.","authors":"Sedigheh Bahmyari, Sanaz Alaee, Zahra Khodabandeh, Tahereh Talaei-Khozani, Mahintaj Dara, Shayesteh Mehdinejadiani, Arezoo Solati","doi":"10.1177/09603271241269019","DOIUrl":"https://doi.org/10.1177/09603271241269019","url":null,"abstract":"Several studies investigated the application of Mesenchymal stem cells (MSCs) for treating spermatogenic disorders. Considering the limitation of MSC application, the present study aimed to compare Wharton's jelly MSCs secretomes, including condition medium (CM) 10-fold concentrated (CM10), 20-fold concentrated CM (CM20), and extracellular vesicles (EVs) to restore busulfan-induced damage on male mice reproduction. So, Wharton's jelly MSCs were cultured, CM was collected, and EVs were isolated. Seventy-two mice were randomly assigned to nine groups, including Control, Busulfan 1 month (1M), Busulfan 2 months (2M), CM10, Busulfan + CM10, CM20, Busulfan + CM20, EVs, and Busulfan + EVs groups. Sperm characteristics, DNA maturity, DNA fragmentation index (DFI), and testicular gene expression were evaluated. Data analysis revealed that CM10 significantly improved sperm plasma membrane integrity, sperm DNA maturity, and DFI in the Busulfan + CM10 group compared to the Busulfan 2M group. Although CM20 and EVs showed a non-significant improvement. Gene expression analysis showed busulfan administration significantly decreased the expression of AR, CREB1, and PLCζ genes, while CM10 significantly restored CREB1 gene expression. The present study demonstrated that CM10 is more effective than CM20 or EVs in reducing busulfan-induced reproductive toxicity.","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":"141857417","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