Pub Date : 2024-08-22eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae136
Yun Gu, Ying Qiu, Yujian Li, Weihua Wen
As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.
{"title":"Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review.","authors":"Yun Gu, Ying Qiu, Yujian Li, Weihua Wen","doi":"10.1093/toxres/tfae136","DOIUrl":"10.1093/toxres/tfae136","url":null,"abstract":"<p><p>As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae133
Preeti Bagri, Vinod Kumar, Kanisht Batra
Background: Moringa oleifera and Tinospora cordifolia is extensively used as an ingredient of food and in traditional medicine for the management of a variety of diseases.
Material and methods: The extracts of leaf of Moringa oleifera and stem of Tinospora cordifolia were assessed to examine their ability to inhibit the oxidative DNA damage (by DNA protection assay), cytoprotective and genoprotective potential (by Comet assay) in V79 cells individually and in combinations.
Result: It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA. M. oleifera extract (160 and 320 μg/mL) and Tinospora cordifolia extract (640, 1,280 and 2,560 μg/mL) individually showed higher DNA protection activity. M. oleifera (1,280 μg/mL) combined with Tinospora cordifolia (640 μg/mL) showed best cytoprotective and genoprotective activities among different concentration combinations and various concentrations of individual plants in V79 cell line against hydrogen peroxide induced cytotoxicity and genotoxicity.
Conclusion: This study demonstrates the cytoprotective and genoprotective activity of M. oleifera and Tinospora cordifolia individually or in combination.
背景:Moringa oleifera 和 Tinospora cordifolia 被广泛用作食品原料和传统药物,用于治疗多种疾病:材料和方法:评估了油辣木叶和虎耳草茎的提取物,以检查它们单独和组合抑制 V79 细胞氧化 DNA 损伤(DNA 保护试验)、细胞保护和基因保护潜力(彗星试验)的能力:结果:研究发现,这些提取物能显著抑制 pUC18 质粒 DNA 的 OH 依赖性损伤。油橄榄提取物(160 和 320 μg/mL)和椴树提取物(640、1,280 和 2,560 μg/mL)单独显示出较高的 DNA 保护活性。在不同浓度组合和不同浓度的单株植物中,M. oleifera(1,280 μg/mL)与Tinospora cordifolia(640 μg/mL)组合在V79细胞系中对过氧化氢诱导的细胞毒性和基因毒性表现出最佳的细胞保护和基因保护活性:本研究证明了油橄榄和虎耳草单独或混合使用具有细胞保护和基因保护活性。
{"title":"Assessment of cytoprotective and genoprotective effects of <i>Moringa oleifera</i> and <i>Tinospora cordifolia</i> extracts in vitro.","authors":"Preeti Bagri, Vinod Kumar, Kanisht Batra","doi":"10.1093/toxres/tfae133","DOIUrl":"10.1093/toxres/tfae133","url":null,"abstract":"<p><strong>Background: </strong><i>Moringa oleifera</i> and <i>Tinospora cordifolia</i> is extensively used as an ingredient of food and in traditional medicine for the management of a variety of diseases.</p><p><strong>Material and methods: </strong>The extracts of leaf of <i>Moringa oleifera</i> and stem of <i>Tinospora cordifolia</i> were assessed to examine their ability to inhibit the oxidative DNA damage (by DNA protection assay), cytoprotective and genoprotective potential (by Comet assay) in V79 cells individually and in combinations.</p><p><strong>Result: </strong>It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA. <i>M. oleifera</i> extract (160 and 320 μg/mL) and <i>Tinospora cordifolia</i> extract (640, 1,280 and 2,560 μg/mL) individually showed higher DNA protection activity. <i>M. oleifera</i> (1,280 μg/mL) combined with <i>Tinospora cordifolia</i> (640 μg/mL) showed best cytoprotective and genoprotective activities among different concentration combinations and various concentrations of individual plants in V79 cell line against hydrogen peroxide induced cytotoxicity and genotoxicity.</p><p><strong>Conclusion: </strong>This study demonstrates the cytoprotective and genoprotective activity of M. oleifera and Tinospora cordifolia individually or in combination.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer.
{"title":"Low expression of Lnc-ENST00000535078 inhibits the migration, invasion, and enhances apoptosis of CTPE-induced malignantly transformed BEAS-2B cells.","authors":"Ping Lu, Liu Yang, Yanting Lei, Yuezeng Zhao, Zhihao Tang, Pingping Shang, Xiaolei Zhou, Pengpeng Wang, Wei Wang, Feifei Feng, Qiao Zhang","doi":"10.1093/toxres/tfae121","DOIUrl":"10.1093/toxres/tfae121","url":null,"abstract":"<p><p>Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae130
Muhammad Ishaq, Liang Zhao, Mohamed Mohamed Soliman, Saed Althobaiti, Helal F Al-Harthi, Shatha B Albattal, Wang Chengtao
As known, gout a metabolic disease due to the urate crystals deposition in the joints and affect human health and state. Humans are looking for safe natural remedies from plants with safe, low cost and high effect on their health. Sinapic acid (SA) is found in plants and used as phytoconstituent in human diets. SA has strong antioxidant activity, bone-regenerative, anti-cancer, anti-allergic, and antidiabetic effects. The current study was outlined to confirm the anti-gout potential of SA against monosodium urate crystals (MSU)-induced gouty arthritis in mice. Positive gouty arthritis was conducted by administration of colchicine and MSU in the hind paw. SA was orally administered to negative and positive MSU arthritic mice at 25 and 50 mg/kg, one-hour before MSU injection (100 μg/kg intra-articular). At the end of the experiment, sampling was done for serum, histopathology, oxidative stress and gene expression analysis. The results showed that SA significantly recovered the joint edema and recovered MSU crystals-showed histopathological changes. The production of cytokines, leukocyte recruitment, oxidative stress, and nucleotide-binding domain, leucinerich-containing family, pyrin domain-containing-3 (NLRP3)-inflammasome genes expressions were increased in positive arthritic mice and ameliorated significantly by SA administration. Moreover, SA showed ameliorative impacts on air pouch model of mice as reported by the down regulation in the expression of inflammation related blood cells, proinflammatory cytokines and other transcriptional genes. In conclusion, sinapic acid showed a potential therapeutic use against side effects accompanying gouty arthritis and is good as a supplement against inflammation associated disorders.
{"title":"Ameliorative impacts of Sinapic acid against monosodium urate crystal-induced gouty arthritis and inflammation through different signaling pathways.","authors":"Muhammad Ishaq, Liang Zhao, Mohamed Mohamed Soliman, Saed Althobaiti, Helal F Al-Harthi, Shatha B Albattal, Wang Chengtao","doi":"10.1093/toxres/tfae130","DOIUrl":"10.1093/toxres/tfae130","url":null,"abstract":"<p><p>As known, gout a metabolic disease due to the urate crystals deposition in the joints and affect human health and state. Humans are looking for safe natural remedies from plants with safe, low cost and high effect on their health. Sinapic acid (SA) is found in plants and used as phytoconstituent in human diets. SA has strong antioxidant activity, bone-regenerative, anti-cancer, anti-allergic, and antidiabetic effects. The current study was outlined to confirm the anti-gout potential of SA against monosodium urate crystals (MSU)-induced gouty arthritis in mice. Positive gouty arthritis was conducted by administration of colchicine and MSU in the hind paw. SA was orally administered to negative and positive MSU arthritic mice at 25 and 50 mg/kg, one-hour before MSU injection (100 μg/kg intra-articular). At the end of the experiment, sampling was done for serum, histopathology, oxidative stress and gene expression analysis. The results showed that SA significantly recovered the joint edema and recovered MSU crystals-showed histopathological changes. The production of cytokines, leukocyte recruitment, oxidative stress, and nucleotide-binding domain, leucinerich-containing family, pyrin domain-containing-3 (NLRP3)-inflammasome genes expressions were increased in positive arthritic mice and ameliorated significantly by SA administration. Moreover, SA showed ameliorative impacts on air pouch model of mice as reported by the down regulation in the expression of inflammation related blood cells, proinflammatory cytokines and other transcriptional genes. In conclusion, sinapic acid showed a potential therapeutic use against side effects accompanying gouty arthritis and is good as a supplement against inflammation associated disorders.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae135
Khadeejah Alsolami, Reham Z Hamza
Background: Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS).
Objectives: Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress.
Methods: Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues.
Results: The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group.
Conclusion: The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats.
{"title":"Orlistat and metformin combination ameliorates obesity-induced renal injury via suppressing renal oxidative stress in male rats.","authors":"Khadeejah Alsolami, Reham Z Hamza","doi":"10.1093/toxres/tfae135","DOIUrl":"10.1093/toxres/tfae135","url":null,"abstract":"<p><strong>Background: </strong>Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS).</p><p><strong>Objectives: </strong>Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress.</p><p><strong>Methods: </strong>Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues.</p><p><strong>Results: </strong>The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group.</p><p><strong>Conclusion: </strong>The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae131
Nagat Fawzy Nawar, Doha Mohammad Beltagy, Tarek Mostafa Mohamed, Ehab Mostafa Tousson, Mai Mahmoud El-Keey
The relationship between amyloid beta (Aβ) and oxidative stress (OS), both prominent factors in Alzheimer's disease-related neural degeneration, is deeply interconnected. The cleavage of the extracellular domain of Amyloid precursor protein (APP) and phosphorylating different substrates, respectively, the β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) and Glycogen synthase kinase-3-beta (GSK-3β) enzymes initiate the synthesis of Aβ, which causes cognitive deficits in AD. This study aimed to explore the protective potential of Coenzyme Q10 (CoQ10). It also sought to uncover any synergistic effects when combined with donepezil, an acetylcholinesterase inhibitor, in treating Alzheimer's disease in male albino rats, focusing on the modulation of the BACE-1/GSK-3β pathway. The experiment involved 70 rats categorized into different groups: control, donepezil alone, CoQ10 alone, AD-model, donepezil co-treatment, CoQ10 co-treatment, and CoQ10 + donepezil combination. Various assessments, such as cholinesterase activity, oxidative stress, serum iron profile, Brain Derived Neurotrophic Factor (BDNF), Tau protein, β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), phosphatase and tensin homolog (Pten), and Glycogen synthase kinase-3-beta (GSK-3β), were conducted on behavioral and biochemical aspects. CoQ10 treatment demonstrated memory improvement, enhanced locomotion, and increased neuronal differentiation, mainly through the inhibition of the dual BACE-1/GSK-3β. These findings were substantiated by histological and immunohistological examinations of the hippocampus.
{"title":"Anti-oxidant activity of coenzyme Q10 against AlCl<sub>3</sub>/D-galactose in albino rat induced cognitive dysfunctions: Behavioral, biochemical, and BACE-1/GSK-3β alterations.","authors":"Nagat Fawzy Nawar, Doha Mohammad Beltagy, Tarek Mostafa Mohamed, Ehab Mostafa Tousson, Mai Mahmoud El-Keey","doi":"10.1093/toxres/tfae131","DOIUrl":"10.1093/toxres/tfae131","url":null,"abstract":"<p><p>The relationship between amyloid beta (Aβ) and oxidative stress (OS), both prominent factors in Alzheimer's disease-related neural degeneration, is deeply interconnected. The cleavage of the extracellular domain of Amyloid precursor protein (APP) and phosphorylating different substrates, respectively, the β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) and Glycogen synthase kinase-3-beta (GSK-3β) enzymes initiate the synthesis of Aβ, which causes cognitive deficits in AD. This study aimed to explore the protective potential of Coenzyme Q10 (CoQ10). It also sought to uncover any synergistic effects when combined with donepezil, an acetylcholinesterase inhibitor, in treating Alzheimer's disease in male albino rats, focusing on the modulation of the BACE-1/GSK-3β pathway. The experiment involved 70 rats categorized into different groups: control, donepezil alone, CoQ10 alone, AD-model, donepezil co-treatment, CoQ10 co-treatment, and CoQ10 + donepezil combination. Various assessments, such as cholinesterase activity, oxidative stress, serum iron profile, Brain Derived Neurotrophic Factor (BDNF), Tau protein, β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), phosphatase and tensin homolog (Pten), and Glycogen synthase kinase-3-beta (GSK-3β), were conducted on behavioral and biochemical aspects. CoQ10 treatment demonstrated memory improvement, enhanced locomotion, and increased neuronal differentiation, mainly through the inhibition of the dual BACE-1/GSK-3β. These findings were substantiated by histological and immunohistological examinations of the hippocampus.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae132
Xiuli Li, Xuefei Li, Yinan Liang
Background: Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory.
Objective: This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment.
Methods: SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p.
Results: Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions . silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p.
Conclusion: Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression.
{"title":"Silencing CircHIPK3 improves sevoflurane-explore learning and memory dysfunction and nerve damage via enhancing miR-338-3p.","authors":"Xiuli Li, Xuefei Li, Yinan Liang","doi":"10.1093/toxres/tfae132","DOIUrl":"10.1093/toxres/tfae132","url":null,"abstract":"<p><strong>Background: </strong>Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory.</p><p><strong>Objective: </strong>This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment.</p><p><strong>Methods: </strong>SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p.</p><p><strong>Results: </strong>Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions . silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p.</p><p><strong>Conclusion: </strong>Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae129
Sinan Ince, Hasan Huseyin Demirel, Ezgi Nur Demirkapi, Ismail Kucukkurt, Abdullah Eryavuz, Damla Arslan-Acaroz, Ulas Acaroz, Ali Tureyen
In the present study, we investigated the protective effect of magnolin (MAG) against oxidative stress induced by cyclophosphamide (CP) and its role in the Nrf2/HO-1 signaling pathway. Rats were administered MAG (1 mg/kg, i.p.) for 14 days and CP (75 mg/kg, i.p.) on the 14th day. CP administration increased tissue damage, as evidenced by elevated levels of transaminases (aspartate and alanine), alkaline phosphatase, and renal parameters (blood urea nitrogen and creatinine). Additionally, 8-hydroxy-2'-deoxyguanosine and malondialdehyde levels were increased, whereas glutathione levels, along with catalase and superoxide dismutase activities, decreased in CP-treated rats. CP also down-regulated the expression of Bcl-2, HO-1, Nrf2, and NQO-1, while up-regulating Bax, Cas-3, TNF-α, Cox-2, iNOS, IL-6, IL-1β, and NFκB in liver and kidney tissues. In addition, CP treatment caused histopathological changes in heart, lung, liver, kidney, brain, and testis tissues. Treatment with MAG improved biochemical and oxidative stress parameters and prevented histopathological changes in CP-treated rats. Moreover, MAG suppressed the expression of inflammatory cytokines and apoptosis markers. In conclusion, MAG effectively prevented CP-induced toxicity by reducing oxidative stress, inflammation, and apoptosis, with its protective efficacy associated with the up-regulation of Nrf2/HO-1 signaling.
{"title":"Magnolin alleviates cyclophosphamide-induced oxidative stress, inflammation, and apoptosis via <i>Nrf2/HO-1</i> signaling pathway.","authors":"Sinan Ince, Hasan Huseyin Demirel, Ezgi Nur Demirkapi, Ismail Kucukkurt, Abdullah Eryavuz, Damla Arslan-Acaroz, Ulas Acaroz, Ali Tureyen","doi":"10.1093/toxres/tfae129","DOIUrl":"10.1093/toxres/tfae129","url":null,"abstract":"<p><p>In the present study, we investigated the protective effect of magnolin (MAG) against oxidative stress induced by cyclophosphamide (CP) and its role in the <i>Nrf2/HO-1</i> signaling pathway. Rats were administered MAG (1 mg/kg, i.p.) for 14 days and CP (75 mg/kg, i.p.) on the 14th day. CP administration increased tissue damage, as evidenced by elevated levels of transaminases (aspartate and alanine), alkaline phosphatase, and renal parameters (blood urea nitrogen and creatinine). Additionally, 8-hydroxy-2'-deoxyguanosine and malondialdehyde levels were increased, whereas glutathione levels, along with catalase and superoxide dismutase activities, decreased in CP-treated rats. CP also down-regulated the expression of <i>Bcl-2, HO-1, Nrf2,</i> and <i>NQO-1</i>, while up-regulating <i>Bax, Cas-3, TNF-</i>α<i>, Cox-2, iNOS, IL-6, IL-1β,</i> and <i>NFκB</i> in liver and kidney tissues. In addition, CP treatment caused histopathological changes in heart, lung, liver, kidney, brain, and testis tissues. Treatment with MAG improved biochemical and oxidative stress parameters and prevented histopathological changes in CP-treated rats. Moreover, MAG suppressed the expression of inflammatory cytokines and apoptosis markers. In conclusion, MAG effectively prevented CP-induced toxicity by reducing oxidative stress, inflammation, and apoptosis, with its protective efficacy associated with the up-regulation of <i>Nrf2/HO-1</i> signaling.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986835","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}
Pub Date : 2024-08-13eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae128
Tunahan Tasci, Banu Orta-Yilmaz, Yasemin Aydin, Mahmut Caliskan
In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 μM to 10 μM) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells.
{"title":"N-acetylcysteine attenuates sodium arsenite-induced oxidative stress and apoptosis in embryonic fibroblast cells.","authors":"Tunahan Tasci, Banu Orta-Yilmaz, Yasemin Aydin, Mahmut Caliskan","doi":"10.1093/toxres/tfae128","DOIUrl":"10.1093/toxres/tfae128","url":null,"abstract":"<p><p>In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 μM to 10 μM) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974528","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}
Pub Date : 2024-08-11eCollection Date: 2024-08-01DOI: 10.1093/toxres/tfae127
Aylin Balci-Ozyurt, Anıl Yirun, Deniz Arca Cakır, İbrahim Ozcelik, Merve Bacanli, Gizem Ozkemahli, Suna Sabuncuoglu, Nursen Basaran, Pınar Erkekoglu
Introduction: Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and "low dose toxicity". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.
Methods: In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects.
Conclusion: Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.
简介:双酚被广泛用于生产聚碳酸酯塑料和树脂涂料。双酚 A(BPA)被认为会导致多种不良影响和 "低剂量毒性"。随着人们寻找双酚 A 的替代物质,其他双酚衍生物(即双酚 F(BPF)和双酚 S(BPS))的使用也在增加:在本研究中,我们旨在评估双酚衍生物对 HepG2 细胞免疫和凋亡标志物以及 DNA 损伤的硅学预测抑制浓度 50s(pIC50s)。此外,还比较测定了双酚 A、双酚 F 和双酚 S 对细胞凋亡、基因毒性和免疫毒性的影响。通过检测不同的 Caspase 活性来评估双酚对细胞凋亡的影响。通过测量 8-hydroxy-2'-deoxyguanosine (8-OHdG) 和 8-oxoguanine glycosylase (OGG1) 的水平,评估了双酚的遗传毒性效应。为了确定双酚衍生物的免疫毒性作用,测量了白细胞介素 4(IL-4)和白细胞介素 10(IL-10)、转化生长因子 beta(TGF-β)和肿瘤坏死因子-α(TNF-α)的水平。结果显示硅学数据表明,所有双酚在低剂量时都可能导致免疫和细胞凋亡标志物的改变以及 DNA 损伤。体外数据显示,所有双酚衍生物在抑制浓度为 30s (IC30s)时都会影响免疫标记物。此外,BPF 和 BPS 还可能具有凋亡免疫毒性作用:结论:要进一步研究替代性双酚衍生物的毒性效应,还需要进行硅学和体内研究。
{"title":"Comparative in silico and in vitro evaluation of possible toxic effects of bisphenol derivatives in HepG2 cells.","authors":"Aylin Balci-Ozyurt, Anıl Yirun, Deniz Arca Cakır, İbrahim Ozcelik, Merve Bacanli, Gizem Ozkemahli, Suna Sabuncuoglu, Nursen Basaran, Pınar Erkekoglu","doi":"10.1093/toxres/tfae127","DOIUrl":"10.1093/toxres/tfae127","url":null,"abstract":"<p><strong>Introduction: </strong>Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and \"low dose toxicity\". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.</p><p><strong>Methods: </strong>In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC<sub>30</sub>s). In addition, BPF and BPS may also have apoptotic immunotoxic effects.</p><p><strong>Conclusion: </strong>Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915525","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}