Toxicology Mechanisms and Methods最新文献_第7页

Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1β, and IL-6 pathway. 富含γ-亚麻酸和D/L-α-生育酚醋酸酯的月见草油通过TNF-α、IL1 β和IL6途径减轻了四氯化碳诱导的雄性大鼠肝损伤模型。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-01-09 DOI: 10.1080/15376516.2023.2301357

Heba Nageh Gad El-Hak, Safaa M Kishk, Heba M A Abdelrazek

{"title":"Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1β, and IL-6 pathway.","authors":"Heba Nageh Gad El-Hak, Safaa M Kishk, Heba M A Abdelrazek","doi":"10.1080/15376516.2023.2301357","DOIUrl":"10.1080/15376516.2023.2301357","url":null,"abstract":"The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male Albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL-1β, IL-6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL-1β, IL-6, and TNF-α gene expressions were induced by CCl4 treatment. The PO/CCl4-treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulations the gene expressions of TNF-α, IL1-β and IL-6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"469-483"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080931","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

Sulforaphane suppresses cell proliferation and induces apoptosis in glioma via the ACTL6A/PGK1 axis. 红景天通过 ACTL6A/PGK1 轴抑制胶质瘤细胞增殖并诱导其凋亡。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-01-25 DOI: 10.1080/15376516.2024.2306375

Zi-Tan Peng, Rong Hu, Jing-Yu Fu

{"title":"Sulforaphane suppresses cell proliferation and induces apoptosis in glioma via the ACTL6A/PGK1 axis.","authors":"Zi-Tan Peng, Rong Hu, Jing-Yu Fu","doi":"10.1080/15376516.2024.2306375","DOIUrl":"10.1080/15376516.2024.2306375","url":null,"abstract":"This study aimed to examine the expression and biological functions of ACTL6A in glioma cells (U251), the effects of sulforaphane on the growth of U251 cells and the involvement of the ACTL6A/PGK1 pathway in those effects. The U251 cell line was transfected with ACTL6A over-expression plasmids to upregulate the protein, or with ACTL6A inhibitor to underexpress it, then treated with different concentrations of sulforaphane. Cell viability, proliferation, and apoptosis were assessed using standard assays, and levels of mRNAs encoding ACTL6A, PGK1, cyclin D1, Myc, Bax or Bcl-2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). ACTL6A and PGK1 were expressed at higher levels in glioma cell lines than in normal HEB cells. ACTL6A overexpression upregulated PGK1, whereas ACTL6A inhibition had the opposite effect. ACTL6A overexpression induced proliferation, whereas its inhibition repressed proliferation, enhanced apoptosis, and halted the cell cycle. Moreover, sulforaphane suppressed the growth of U251 cells by inactivating the ACTL6A/PGK1 axis. ACTL6A acts via PGK1 to play a critical role in glioma cell survival and proliferation, and sulforaphane targets it to inhibit glioma.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"507-516"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466588","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

Optimized rat models better mimic patients with irinotecan-induced severe diarrhea. 优化后的大鼠模型能更好地模拟伊立替康诱发的严重腹泻患者。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-02-23 DOI: 10.1080/15376516.2024.2316003

Zicong Zheng, Ting Du, Song Gao, Taijun Yin, Li Li, Lijun Zhu, Rashim Singh, Rongjin Sun, Ming Hu

{"title":"Optimized rat models better mimic patients with irinotecan-induced severe diarrhea.","authors":"Zicong Zheng, Ting Du, Song Gao, Taijun Yin, Li Li, Lijun Zhu, Rashim Singh, Rongjin Sun, Ming Hu","doi":"10.1080/15376516.2024.2316003","DOIUrl":"10.1080/15376516.2024.2316003","url":null,"abstract":"Irinotecan-induced severe diarrhea (IISD) not only limits irinotecan's application but also significantly affects patients' quality of life. However, existing animal models often inadequately represent the dynamics of IISD development, progression, and resolution across multiple chemotherapy cycles, yielding non-reproducible and highly variable response with limited clinical translation. Our studies aim to establish a reproducible and validated IISD model that better mimics the pathophysiology progression observed in patients, enhancing translational potential. We investigated the impact of dosing regimens (including different dose, infusion time, and two cycles of irinotecan administration), sex, age, tumor-bearing conditions, and irinotecan formulation on the IISD incidence and severity in mice and rats. Lastly, we investigated above factors' impact on pharmacokinetics of irinotecan, intestinal injury, and carboxylesterase activities. In summary, we successfully established a standard model establishment procedure for an optimized IISD model with highly reproducible severe diarrhea incidence rate (100%) and a low mortality rate (11%) in F344 rats. Additionally, the rats tolerated at least two cycles of irinotecan chemotherapy treatment. In contrast, the mouse model exhibited suboptimal IISD incidence rates (60%) and an extremely high mortality rate (100%). Notably, dosing regimen, age and tumor-bearing conditions of animals emerged as critical factors in IISD model establishment. In conclusion, our rat IISD model proves superior in mimicking pathophysiology progression and characteristics of IISD in patients, which stands as an effective tool for mechanism and efficacy studies in future chemotherapy-induced gut toxicity research.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"572-583"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932973","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}

引用次数: 0

An improved method for toxicological profiling of chemical substances. 改进的化学物质毒理学分析方法。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-02-12 DOI: 10.1080/15376516.2024.2310012

Michael Oluwatoyin Daniyan, Nusrat Omotayo Omisore, Oluwole Isaac Adeyemi, Ayokunmi Stephen Olusa, Samuel Folarin Olaniran, Idris Ajayi Oyemitan, Moses Atanda Akanmu, Gbola Olayiwola

{"title":"An improved method for toxicological profiling of chemical substances.","authors":"Michael Oluwatoyin Daniyan, Nusrat Omotayo Omisore, Oluwole Isaac Adeyemi, Ayokunmi Stephen Olusa, Samuel Folarin Olaniran, Idris Ajayi Oyemitan, Moses Atanda Akanmu, Gbola Olayiwola","doi":"10.1080/15376516.2024.2310012","DOIUrl":"10.1080/15376516.2024.2310012","url":null,"abstract":"Toxicity profiling is an integral part of the drug discovery pipeline. The 3Rs principle-Replacement, Reduction, and Refinement, is considered a golden rule in determining the most appropriate approach for toxicity studies. The acute toxicity study with proper estimate of median lethal dose (LD50) is usually an initial procedure for the determination of most suitable test doses for preclinical toxicological and pharmacological profiling. Several methods, which have been devised to determine the LD50, are faced with the challenge of using a large number of animals and time constraints. Despite the inherent advantage of the newer OECD Test Guidelines, the increasing concerns among toxicologists, the regulatory authorities and the general public, on the need to adhere to 3Rs principle, necessitated the need for an improved approach. Such an approach should not only minimize the time and number of animals required, but also take into cognizance animal welfare, and give accurate, comparable, and reproducible results across laboratories. While taking advantage of the inherent merits of the existing methods, here is presented the mathematical basis and evaluation of an improved method for toxicity profiling of test substances and estimation of LD50. The method makes use of the generated Table of values for the selection of appropriate test doses. Our proposed method has capacities to optimize the time and number of animal use, ensure more reliable and reproducible results across laboratories, allow for easy selection of doses for subsequent toxicity profiling, and be adaptable to other biological screening beyond toxicity studies.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"545-562"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547371","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

Antioxidant and antiproliferative effects of Teucrium polium extract: computational and in vivo study in rats. 柚木提取物的抗氧化和抗增殖作用：对大鼠的计算和体内研究。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-01-26 DOI: 10.1080/15376516.2023.2301670

Fatma Rahmouni, Latifa Hamdaoui, Mongi Saoudi, Riadh Badraoui, Tarek Rebai

{"title":"Antioxidant and antiproliferative effects of Teucrium polium extract: computational and in vivo study in rats.","authors":"Fatma Rahmouni, Latifa Hamdaoui, Mongi Saoudi, Riadh Badraoui, Tarek Rebai","doi":"10.1080/15376516.2023.2301670","DOIUrl":"10.1080/15376516.2023.2301670","url":null,"abstract":"The current study aimed to assess the antioxidant and antiproliferative effects of teucrium polium extract: computational and in vivo study in rats. Three groups of animals: Group (i) constitute the control group; Group (ii) HeLa group received an intrafemoral inoculation of HeLa cells and Group (iii) constitue the combination between HeLa + T. polium. The plant was administered by gavage. Our results revealed that HeLa cell injection showed an elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), creatinine, urea, calcium and phosphorus. The pretreatment with the plant extract reduced the level of these parameters. Injection of HeLa cells showed a significant decrease in phosphorus and calcium respectively. However, the pretreatment by T. polium modulated the level of these two minerals. Rats treated with HeLa cells line showed an increase in the level of lipid peroxidation as evaluated by the TBARS substances, at the same time, a significant decreases in SOD, CAT and GPx activities were noted in the HeLa group compared to the control. On the other hand, pretreatment with the plant improved the level of these enzymes. Our results revealed that T.polium has a therapeutic effect on some health problems. HeLa cell line induced a small infiltration in liver and kidney. T. polium reduced the damage in both liver and kidney, but did not reveal any proliferation of tumor cells from trabecular bone tissue. The computational study revealed that T. polium compound bound with high free binding energies and established promising network of molecular interactions with COX-2 and TNF-α macromolecules.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"495-506"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080930","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

Evidence of binding between diethylstilbestrol (DES) and the goldfish (Carassius auratus) membrane progesterone receptor α. 己烯雌酚（DES）与金鱼（Carassius auratus）膜孕酮受体 α 结合的证据。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-02-05 DOI: 10.1080/15376516.2024.2311185

Md Forhad Hossain, Umme Habiba Mustary, Toshinobu Tokumoto

{"title":"Evidence of binding between diethylstilbestrol (DES) and the goldfish (Carassius auratus) membrane progesterone receptor α.","authors":"Md Forhad Hossain, Umme Habiba Mustary, Toshinobu Tokumoto","doi":"10.1080/15376516.2024.2311185","DOIUrl":"10.1080/15376516.2024.2311185","url":null,"abstract":"Background: In a previous study, diethylstilbestrol (DES) was shown to induce oocyte maturation in fish. In the present study, the interaction of DES on goldfish membrane progesterone receptor α (GmPRα) was investigated using a competitive binding assay with radiolabeled steroids. The results indicate that DES exerts its effects on membrane progesterone receptor alpha (mPRα) and induces oocyte maturation through nongenomic steroid mechanisms. This study provides empirical data that demonstrate the binding between DES and GmPRα.Methods: Binding of DES to GmPRα was achieved by using radiolabeled DES and recombinant GmPRα expressed in culture cells or purified GmPRα proteins that coupled to graphene quantum dots (GQDs). Additionally, the competitive binding of fluorescently labeled progesterone to GmPRα-expressing cells was evaluated.Results: Although significant nonspecific binding of radiolabeled DES to the cell membrane that expresses GmPRα has been observed, specific binding of DES to GmPRα has been successfully identified in the presence of digitonin. Furthermore, the specific binding of DES to GmPRα was confirmed by a binding assay using GQD-GmPRα. The radiolabeled DES was shown to bind to GQD-GmPRα. Additionally, the competition for the binding of fluorescently labeled progesterone to GmPRα-expressing cells was achieved with the DES.Conclusions: The results of the experiments revealed that DES binds to GmPRα. Thus, it can be concluded that DES induces goldfish oocyte maturation by binding to GmPRα.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"563-571"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693039","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

Use of TLM derived models to estimate toxicity of weathered MC252 oil based on conventional chemical data and the potential impact of unresolved polar components. 根据常规化学数据和未解决的极性成分的潜在影响，使用 TLM 衍生模型估算风化 MC252 石油的毒性。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-02-28 DOI: 10.1080/15376516.2024.2321165

Liv-Guri Faksness, Dag Altin, Bjørn Henrik Hansen, Trond Nordtug

{"title":"Use of TLM derived models to estimate toxicity of weathered MC252 oil based on conventional chemical data and the potential impact of unresolved polar components.","authors":"Liv-Guri Faksness, Dag Altin, Bjørn Henrik Hansen, Trond Nordtug","doi":"10.1080/15376516.2024.2321165","DOIUrl":"10.1080/15376516.2024.2321165","url":null,"abstract":"Target lipid model (TLM) and toxic unit (TU) approaches were applied to ecotoxicity and chemistry data from low-energy WAFs (LE-WAFs) of source and weathered crude oils originating from the Deepwater Horizon oil spill. The weathered oils included artificially weathered oils and naturally weathered samples collected in the Gulf of Mexico after the spill. Oil weathering greatly reduced the concentrations of identified LE-WAF components, however, the mass of uncharacterized polar material (UPC) in the LE-WAFs remained largely unchanged during the weathering process. While the TLM-derived calculations displayed a significant decrease in toxicity (TUs) for the heavily weathered oils, copepod toxicity, expressed as LC10-based TUs, were comparable between LE-WAFs of fresh and weathered oils. The discrepancy between observed and predicted toxicity for the LE-WAFs of artificially weathered oils may be related to limitations by the chemical analyses or increased toxicity due to generation of new unknown compounds during the weathering process.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"596-605"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906472","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

The regulatory effects of pomiferin dietary on nickel-induced hepatic injury in Sprague-Dawley rats; action mechanisms and signaling pathways. 柿皮素膳食对镍诱导的 Sprague-Dawley 大鼠肝损伤的调节作用；作用机制和信号通路。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-01-15 DOI: 10.1080/15376516.2023.2301667

Gulsah Yildiz Deniz, Fatime Geyikoglu, Serdar Altun

{"title":"The regulatory effects of pomiferin dietary on nickel-induced hepatic injury in Sprague-Dawley rats; action mechanisms and signaling pathways.","authors":"Gulsah Yildiz Deniz, Fatime Geyikoglu, Serdar Altun","doi":"10.1080/15376516.2023.2301667","DOIUrl":"10.1080/15376516.2023.2301667","url":null,"abstract":"The new technological applications of nickel (Ni) raise concerns over its harmful effects on the environment and human health. Pomiferin isolated from Osage orange is evaluated in in vitro and in vivo laboratory bioassays. This study focused the effects of pomiferin on Ni-caused hepatic injury and its underlying mechanisms. With this aim, Sprague-Dawley rats received 10 mg/kg nickel chloride (NiCl2) for 7 d by intraperitoneal injections. Pomiferin was given orally once a day at different doses (75, 150, and 300 mg/kg) for 20 d after exposure to NiCl2. Animals were anesthetized and livers were carefully collected to evaluate oxidative stress, inflammation, vascular injury, and hepatic function. Also, immunofluorescence analysis of apoptosis and DNA damage was performed on rat hepatic tissues. NiCl2 increased MDA production while reducing SOD, CAT, and GPx activity. NiCl2 induced the production of inflammatory cytokines and also platelet activation in hepatic tissue. Moreover, there were significant increases in AST, ALT, and LDH levels. NiCl2 also caused significant pathological changes in hepatic. Additionally, it remarkably induced up-regulations of apoptotic marker and 8-OHdG expressions by immunofluorescence labeling in liver cells. Whereas, pomiferin significantly attenuated lipid peroxidation and increased antioxidant defense system in liver. Also, the use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1β/IL-6. In addition, pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells. Pomiferin seems to counteract the deleterious effects of NiCl2 on hepatic tissue through different cellular and signaling mechanisms.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"484-494"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466751","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

Safety assessment of high fructose corn syrup and fructose used as sweeteners in foods. 食品中用作甜味剂的高果糖玉米糖浆和果糖的安全性评估。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-02-23 DOI: 10.1080/15376516.2024.2318570

Sabire Nur Bulbul, Sevcan Mamur, Deniz Yuzbasioglu, Fatma Unal

{"title":"Safety assessment of high fructose corn syrup and fructose used as sweeteners in foods.","authors":"Sabire Nur Bulbul, Sevcan Mamur, Deniz Yuzbasioglu, Fatma Unal","doi":"10.1080/15376516.2024.2318570","DOIUrl":"10.1080/15376516.2024.2318570","url":null,"abstract":"High Fructose Corn Syrup (HFCS) and Fructose (FR) are widely used sweeteners in many foods and beverages. This study aimed at investigating the cytotoxic effects of HFCS (5%-30%) and FR (62.5-2000 μg/mL) using MTT assay in Human Hepatocellular Carcinoma (HepG2) cells, and genotoxic effects of using Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), Micronuclei (MN) and comet assays in human lymphocytes. HFCS significantly reduced the cell viability in HepG2 cells at between 7.5% and 30% for 24 and 48 h. 30% HFCS caused a very significant toxic effect. FR had a cytotoxic effect in HepG2 cells at all treatments. However, as fructose concentration decreased, the cell viability decreased. HFCS (10%-20%) and FR (250-2000 μg/mL) decreased the mitotic index at higher concentrations. IC50 value was found to be a 15% for 48 h. IC50 value of FR was detected as 62.5 μg/mL for 24 h and 48 h. HFCS significantly increased CAs frequency at 15% and 20%. FR significantly increased the frequency of CAs at 250, 1000, and 2000 μg/mL for 48 h. Both sweeteners increased the frequency of SCEs at all concentrations. HFCS (15% and 20%) and FR (250, 1000, and 2000 μg/mL) induced MN frequency at higher concentrations. HFCS caused DNA damage in comet assay at 10% -30%. FR increased tail intensity and moment at 125-2000 μg/mL and tail length at 62.5, 250 and 500 μg/mL. Therefore, HFCS and FR are clearly seen to be cytotoxic and genotoxic, especially at higher concentrations.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"584-595"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724140","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

PM_2.5-induced DNA oxidative stress in A549 cells and regulating mechanisms by GST DNA methylation and Keap1/Nrf2 pathway. PM2.5诱导的A549细胞DNA氧化应激及GST DNA甲基化和Keap1/Nrf2途径的调控机制

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2024-06-01 Epub Date: 2024-01-31 DOI: 10.1080/15376516.2024.2307967

Ruijin Li, Chao Zhao, Yuexia Zhang, Wei Huang, Jiayi Wang, Guodong Cao, Zongwei Cai

{"title":"PM2.5-induced DNA oxidative stress in A549 cells and regulating mechanisms by GST DNA methylation and Keap1/Nrf2 pathway.","authors":"Ruijin Li, Chao Zhao, Yuexia Zhang, Wei Huang, Jiayi Wang, Guodong Cao, Zongwei Cai","doi":"10.1080/15376516.2024.2307967","DOIUrl":"10.1080/15376516.2024.2307967","url":null,"abstract":"Fine particulate matter (PM2.5) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM2.5. However, the regulating mechanisms of PM2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM2.5 (0, 50, 100 µg/mL, from Taiyuan, China) for 24 h (n = 4). We found that PM2.5 may cause DNA oxidative damage to cells and the elevation of GSTP1 promotes cell resistance to reactive oxygen species (ROS). The Kelch-1ike ECH-associated protein l (Keap1)/nuclear factor NF-E2-related factor 2 (Nrf2) pathway activates the GSTP1. The decrease in the DNA methylation level of the GSTP1 gene enhances GSTP1 expression. GST DNA methylation is associated with reduced levels of 5-methylcytosine (5mC), DNA methyltransferase 1 (DNMT1), and histone deacetylases 3 (HDAC3). The GSTM1 was not sensitive to PM2.5 stimulation. Our findings suggest that PM2.5 activates GSTP1 to defend PM2.5-induced ROS and 8-hydroxy-deoxyguanosine (8-OHdG) formation through the Keap1/Nrf2 signaling pathway and GSTP1 DNA methylation.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"517-526"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642998","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