Pub Date : 2017-02-01DOI: 10.1080/15376516.2016.1258748
S. Shahani, F. Behzadfar, Daniel Jahani, M. Ghasemi, F. Shaki
Abstract Background and purpose: Gentamicin (GM) is used against bacterial infections. The aim of our investigation was to evaluate the role of inflammation and also oxidative damage in nephrotoxic potential of GM and protective effects of Nasturtium officinale (watercress) against GM-induced nephrotoxicity in Wistar rats. Material and methods: The animals were divided into eight groups: control, solvent, GM (80 mg/kg IP), GM with three doses (50, 100 and 200 mg/kg/d) of hydroalcoholic extract of watercress and one group only received high dose of extract and a group which received GM plus vitamin E for 10 consecutive days. Then, the animals were killed and kidney tissues were separated. Finally reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation (LPO), protein carbonyl (PCO), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated. Also, pathological examination and measuring of blood urea nitrogen (BUN) and creatinine (Cr) were done. Results: The administration of GM for 10 d resulted in an increase in kidney markers (BUN and Cr) and pathological changes in kidney tissue. Also, oxidative stress was evident in GM group by increased ROS, LPO and PCO level and GSH oxidation. Increased in inflammation process was shown by increase in NO and TNF-α. Administration of watercress extract was able to protect against deterioration in nephrotoxic markers and suppressed the increase in oxidative stress and inflammation markers. Conclusions: Our study showed the critical role of oxidative damage and inflammation in GM-induced nephrotoxicity that markedly inhibited by administration of watercress. Therefore, watercress can be suggested for prevention of GM-induced nephrotoxicity.
{"title":"Antioxidant and anti-inflammatory effects of Nasturtium officinale involved in attenuation of gentamicin-induced nephrotoxicity","authors":"S. Shahani, F. Behzadfar, Daniel Jahani, M. Ghasemi, F. Shaki","doi":"10.1080/15376516.2016.1258748","DOIUrl":"https://doi.org/10.1080/15376516.2016.1258748","url":null,"abstract":"Abstract Background and purpose: Gentamicin (GM) is used against bacterial infections. The aim of our investigation was to evaluate the role of inflammation and also oxidative damage in nephrotoxic potential of GM and protective effects of Nasturtium officinale (watercress) against GM-induced nephrotoxicity in Wistar rats. Material and methods: The animals were divided into eight groups: control, solvent, GM (80 mg/kg IP), GM with three doses (50, 100 and 200 mg/kg/d) of hydroalcoholic extract of watercress and one group only received high dose of extract and a group which received GM plus vitamin E for 10 consecutive days. Then, the animals were killed and kidney tissues were separated. Finally reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation (LPO), protein carbonyl (PCO), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated. Also, pathological examination and measuring of blood urea nitrogen (BUN) and creatinine (Cr) were done. Results: The administration of GM for 10 d resulted in an increase in kidney markers (BUN and Cr) and pathological changes in kidney tissue. Also, oxidative stress was evident in GM group by increased ROS, LPO and PCO level and GSH oxidation. Increased in inflammation process was shown by increase in NO and TNF-α. Administration of watercress extract was able to protect against deterioration in nephrotoxic markers and suppressed the increase in oxidative stress and inflammation markers. Conclusions: Our study showed the critical role of oxidative damage and inflammation in GM-induced nephrotoxicity that markedly inhibited by administration of watercress. Therefore, watercress can be suggested for prevention of GM-induced nephrotoxicity.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"107 - 114"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1258748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45502039","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}
Abstract Diethylhexyl phthalate (DEHP) is suspected to be an inevitable factor related to metabolic disease. Our previous study demonstrated that excess DEHP could exacerbate non-alcoholic fatty liver disease (NAFLD) in SD rats. Addressing the terra incognita in DEHP-induced metabolic dysfunction, this study used HepG2 cells to investigate the potential mechanisms involved in DEHP-induced toxicity in vitro. The cells were established lipid overload model with oleic acid and BSA, then exposed to different concentrations (5, 10, 25, 50, 100 μmol/l DEHP) of DEHP for further analysis. The Oil Red O staining results showed that DEHP could promote lipid accumulation in cells. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) changed suggested the balance of oxidative stress was disrupted. Additionally, western blot analysis showed that DEHP could promote the expression of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c). By quantifying the expressions of the two proteins, it is of interest to determine that DEHP could promote lipid accumulation in hepatocytes via activating the SREBP-1c and PPARα-signaling pathway.
{"title":"The effects of di 2-ethyl hexyl phthalate (DEHP) on cellular lipid accumulation in HepG2 cells and its potential mechanisms in the molecular level","authors":"Wang Zhang, Xin-yue Shen, Wen-wen Zhang, Hao-Yun Chen, Wei-ping Xu, Wei Wei","doi":"10.1080/15376516.2016.1273427","DOIUrl":"https://doi.org/10.1080/15376516.2016.1273427","url":null,"abstract":"Abstract Diethylhexyl phthalate (DEHP) is suspected to be an inevitable factor related to metabolic disease. Our previous study demonstrated that excess DEHP could exacerbate non-alcoholic fatty liver disease (NAFLD) in SD rats. Addressing the terra incognita in DEHP-induced metabolic dysfunction, this study used HepG2 cells to investigate the potential mechanisms involved in DEHP-induced toxicity in vitro. The cells were established lipid overload model with oleic acid and BSA, then exposed to different concentrations (5, 10, 25, 50, 100 μmol/l DEHP) of DEHP for further analysis. The Oil Red O staining results showed that DEHP could promote lipid accumulation in cells. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) changed suggested the balance of oxidative stress was disrupted. Additionally, western blot analysis showed that DEHP could promote the expression of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c). By quantifying the expressions of the two proteins, it is of interest to determine that DEHP could promote lipid accumulation in hepatocytes via activating the SREBP-1c and PPARα-signaling pathway.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"245 - 252"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1273427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41546962","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}
Pub Date : 2017-02-01DOI: 10.1080/15376516.2016.1258747
Yong Fa Zhang, Jian Ying Yang, Yong Li, W. Zhou
Abstract To explore the toxic mechanism of T-2 toxin on Leydig cells of mice, we would investigate the toxicity and oxidative stress induced by T-2 toxin in the cells. Leydig cells were isolated and cultured with control or T-2 toxin (10−7 M, 10−8 M, or 10−9 M) for 24 h, then cells and supernatants were harvested to examine cell viability, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, expression of messenger RNA (mRNA) related to oxidative stress, malondialdehyde (MDA) content and DNA damage. The cell viability was evaluated in mouse Leydig cells by MTT assay, MDA content and SOD, GSH-Px and CAT activities were measured by routine kits, expression of mRNA related to oxidative stress were examined by quantitative real-time polymerase chain reaction (PCR), and DNA damage was investigated by comet assay. Leydig cells treated with T-2 toxin showed significant reductions in cell viability, SOD, GSH-Px and CAT activities, and expression of mRNA related to oxidative stress, and remarkable increases in MDA content and levels of DNA damage. This study proves that T-2 toxin is toxic to Leydig cells of mice. Furthermore, oxidative stress plays an important role in the above-mentioned negative effects of T-2 toxin.
{"title":"Toxicity and oxidative stress induced by T-2 toxin in cultured mouse Leydig cells","authors":"Yong Fa Zhang, Jian Ying Yang, Yong Li, W. Zhou","doi":"10.1080/15376516.2016.1258747","DOIUrl":"https://doi.org/10.1080/15376516.2016.1258747","url":null,"abstract":"Abstract To explore the toxic mechanism of T-2 toxin on Leydig cells of mice, we would investigate the toxicity and oxidative stress induced by T-2 toxin in the cells. Leydig cells were isolated and cultured with control or T-2 toxin (10−7 M, 10−8 M, or 10−9 M) for 24 h, then cells and supernatants were harvested to examine cell viability, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, expression of messenger RNA (mRNA) related to oxidative stress, malondialdehyde (MDA) content and DNA damage. The cell viability was evaluated in mouse Leydig cells by MTT assay, MDA content and SOD, GSH-Px and CAT activities were measured by routine kits, expression of mRNA related to oxidative stress were examined by quantitative real-time polymerase chain reaction (PCR), and DNA damage was investigated by comet assay. Leydig cells treated with T-2 toxin showed significant reductions in cell viability, SOD, GSH-Px and CAT activities, and expression of mRNA related to oxidative stress, and remarkable increases in MDA content and levels of DNA damage. This study proves that T-2 toxin is toxic to Leydig cells of mice. Furthermore, oxidative stress plays an important role in the above-mentioned negative effects of T-2 toxin.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"100 - 106"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1258747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41593403","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}
Abstract Two yeast enhanced green fluorescence protein (yEGFP) yeast reporter vectors, pR1558-yEGFP and pR406-yEGFP, which are regulated by two RAD54 promoters containing 406-bp and 1558-bp DNA sequences, respectively, were constructed using molecular biological techniques and transformed into yeast for the screening of genotoxins. The constructed biosensors were named W303-1A/R1558-yEGFP and W303-1A/R406-yEGFP. To quantify biosensor performance, both transformed yeast cells were exposed to multiple doses of genotoxins including methylmethane sulfonate (MMS; a DNA alkylating agent), 4-nitroquinoline-N-oxide (4-NQO; a DNA cleavage agent), 5-fluorouracil (5-Fu; an inhibitor of polymerases and topoisomerases) and colchicine and canavanine (affecting other biochemical activities). The yeast bioassay performance was analyzed using fluorescence-activated cell sorting (FACS) and Multi-Mode Reader in a 96-well black microplate. The observed W303-1A/R1558-yEGFP dose-effect relationship was more obvious and the maximum inductions were 5.96-fold (MMS), 2.19-fold (4-NQO) and 2.71-fold (5-Fu); the corresponding values for W303-1A/R406-yEGFP were 2.53-, 1.50- and 1.91-fold, respectively. It is suggested that it is best to select the entire RAD54 promoter when constructing recombinant yeast cells for screening mutagens.
{"title":"Construction and comparison of yeast whole-cell biosensors regulated by two RAD54 promoters capable of detecting genotoxic compounds","authors":"Yongjie Tian, Yixin Lu, Xiuju Xu, Chao Wang, Tianqi Zhou, Xiangming Li","doi":"10.1080/15376516.2016.1266540","DOIUrl":"https://doi.org/10.1080/15376516.2016.1266540","url":null,"abstract":"Abstract Two yeast enhanced green fluorescence protein (yEGFP) yeast reporter vectors, pR1558-yEGFP and pR406-yEGFP, which are regulated by two RAD54 promoters containing 406-bp and 1558-bp DNA sequences, respectively, were constructed using molecular biological techniques and transformed into yeast for the screening of genotoxins. The constructed biosensors were named W303-1A/R1558-yEGFP and W303-1A/R406-yEGFP. To quantify biosensor performance, both transformed yeast cells were exposed to multiple doses of genotoxins including methylmethane sulfonate (MMS; a DNA alkylating agent), 4-nitroquinoline-N-oxide (4-NQO; a DNA cleavage agent), 5-fluorouracil (5-Fu; an inhibitor of polymerases and topoisomerases) and colchicine and canavanine (affecting other biochemical activities). The yeast bioassay performance was analyzed using fluorescence-activated cell sorting (FACS) and Multi-Mode Reader in a 96-well black microplate. The observed W303-1A/R1558-yEGFP dose-effect relationship was more obvious and the maximum inductions were 5.96-fold (MMS), 2.19-fold (4-NQO) and 2.71-fold (5-Fu); the corresponding values for W303-1A/R406-yEGFP were 2.53-, 1.50- and 1.91-fold, respectively. It is suggested that it is best to select the entire RAD54 promoter when constructing recombinant yeast cells for screening mutagens.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"115 - 120"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1266540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48526929","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}
Pub Date : 2017-02-01DOI: 10.1080/15376516.2016.1256460
Mitra Abbasi, B. Small, N. Patel, M. Jamei, S. Polak
Abstract Background and purpose: To determine the predictive performance of in silico models using drug-specific preclinical cardiac electrophysiology data to investigate drug-induced arrhythmia risk (e.g. Torsade de pointes (TdP)) in virtual human subjects. Experimental approach: To assess drug proarrhythmic risk, we used a set of in vitro electrophysiological measurements describing ion channel inhibition triggered by the investigated drugs. The Cardiac Safety Simulator version 2.0 (CSS; Simcyp, Sheffield, UK) platform was used to simulate human left ventricular cardiac myocyte action potential models. Results: This study shows the impact of drug concentration changes on particular ionic currents by using available experimental data. The simulation results display safety threshold according to drug concentration threshold and log (threshold concentration/ effective therapeutic plasma concentration (ETPC)). Conclusion and implications: We reproduced the underlying biophysical characteristics of cardiac cells resulted in effects of drugs associated with cardiac arrhythmias (action potential duration (APD) and QT prolongation and TdP) which were observed in published 3D simulations, yet with much less computational burden.
{"title":"Early assessment of proarrhythmic risk of drugs using the in vitro data and single-cell-based in silico models: proof of concept","authors":"Mitra Abbasi, B. Small, N. Patel, M. Jamei, S. Polak","doi":"10.1080/15376516.2016.1256460","DOIUrl":"https://doi.org/10.1080/15376516.2016.1256460","url":null,"abstract":"Abstract Background and purpose: To determine the predictive performance of in silico models using drug-specific preclinical cardiac electrophysiology data to investigate drug-induced arrhythmia risk (e.g. Torsade de pointes (TdP)) in virtual human subjects. Experimental approach: To assess drug proarrhythmic risk, we used a set of in vitro electrophysiological measurements describing ion channel inhibition triggered by the investigated drugs. The Cardiac Safety Simulator version 2.0 (CSS; Simcyp, Sheffield, UK) platform was used to simulate human left ventricular cardiac myocyte action potential models. Results: This study shows the impact of drug concentration changes on particular ionic currents by using available experimental data. The simulation results display safety threshold according to drug concentration threshold and log (threshold concentration/ effective therapeutic plasma concentration (ETPC)). Conclusion and implications: We reproduced the underlying biophysical characteristics of cardiac cells resulted in effects of drugs associated with cardiac arrhythmias (action potential duration (APD) and QT prolongation and TdP) which were observed in published 3D simulations, yet with much less computational burden.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"88 - 99"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1256460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44764515","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}
Pub Date : 2017-02-01DOI: 10.1080/15376516.2016.1253812
O. Ozsoy, Sinem Aras, Ayse Ozkan, H. Parlak, B. Gemici, N. Uysal, M. Aslan, P. Yargiçoğlu,, A. Agar
Abstract The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.
{"title":"The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats","authors":"O. Ozsoy, Sinem Aras, Ayse Ozkan, H. Parlak, B. Gemici, N. Uysal, M. Aslan, P. Yargiçoğlu,, A. Agar","doi":"10.1080/15376516.2016.1253812","DOIUrl":"https://doi.org/10.1080/15376516.2016.1253812","url":null,"abstract":"Abstract The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"81 - 87"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1253812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46699232","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}
Pub Date : 2017-02-01DOI: 10.1080/15376516.2016.1266541
Jiao Jiang, Henggui Xu, Hetong Wang, Yining Zhang, P. Ya, Chun Yang, Fasheng Li
Abstract Benzo(a)pyrene (BaP) was a well-known environmental pollutant, numerous studies had implicated BaP as a causative agent in human cancer, particularly lung cancer. The lemongrass essential oil (LEO) possessed various pharmacological activities, especially the anti-oxidative stress and cancer prevention. In the current study, human embryonic lung fibroblast (HELF) cells were treated with 25 mM BaP in the absence or presence of 0.5%, 1% or 2.5% LEO and the cell viability and levels of oxidative stress (OS) and DNA damage in the cells were then measured. Nineteen chemical constituents were identified in LEO, with citral being the main component, representing about 68.78%. LEO was able to protect the HELF cells against BaP-induced loss in cell viability, achieving a maximum of 95.58% cell viability at the 0.5% concentration. Treatment of HELF cells with BaP alone significantly increased the level of Malondialdehyde (MDA) and decreased superoxide dismutase (SOD) and catalase (CAT). However, these effects were suppressed when the cells were also treated with LEO, leading to enhanced levels of SOD and CAT activities (2.9- and 2-fold, respectively, compared with BaP treatment only) and reduced the level of MDA in the cells (43% reduction in malondialdehyde level). At the same time, LEO also reduced the level of DNA damage, as shown by a reduced level of 8-hydroxy-deoxyguanosine (8-OHdG). Taken together, the results showed that LEO offered protection against BaP-induced OS and DNA damage, suggesting that LEO could be a promising agent for lung cancer chemoprevention.
摘要:苯并(a)芘(BaP)是一种众所周知的环境污染物，许多研究表明BaP是人类癌症，特别是肺癌的病原体。柠檬草精油具有多种药理活性，尤其是抗氧化应激和防癌作用。在本研究中，用25 mM BaP处理人胚胎肺成纤维细胞(HELF)，在不含或存在0.5%、1%或2.5% LEO的情况下，测量细胞活力、氧化应激(OS)水平和细胞DNA损伤。LEO共鉴定出19种化学成分，其中以柠檬醛为主要成分，约占68.78%。LEO能够保护HELF细胞免受bap诱导的细胞活力丧失，在0.5%浓度下达到95.58%的细胞活力最大值。单独用BaP处理HELF细胞可显著提高丙二醛(MDA)水平，降低超氧化物歧化酶(SOD)和过氧化氢酶(CAT)。然而，当细胞也被LEO处理时，这些作用被抑制，导致SOD和CAT活性水平提高(分别是仅BaP处理的2.9倍和2倍)，并降低细胞中的MDA水平(丙二醛水平降低43%)。同时，LEO还降低了DNA损伤水平，8-羟基脱氧鸟苷(8-OHdG)水平降低。综上所述，结果表明，LEO对bap诱导的OS和DNA损伤具有保护作用，提示LEO可能是一种有前景的肺癌化学预防药物。
{"title":"Protective effects of lemongrass essential oil against benzo(a)pyrene-induced oxidative stress and DNA damage in human embryonic lung fibroblast cells","authors":"Jiao Jiang, Henggui Xu, Hetong Wang, Yining Zhang, P. Ya, Chun Yang, Fasheng Li","doi":"10.1080/15376516.2016.1266541","DOIUrl":"https://doi.org/10.1080/15376516.2016.1266541","url":null,"abstract":"Abstract Benzo(a)pyrene (BaP) was a well-known environmental pollutant, numerous studies had implicated BaP as a causative agent in human cancer, particularly lung cancer. The lemongrass essential oil (LEO) possessed various pharmacological activities, especially the anti-oxidative stress and cancer prevention. In the current study, human embryonic lung fibroblast (HELF) cells were treated with 25 mM BaP in the absence or presence of 0.5%, 1% or 2.5% LEO and the cell viability and levels of oxidative stress (OS) and DNA damage in the cells were then measured. Nineteen chemical constituents were identified in LEO, with citral being the main component, representing about 68.78%. LEO was able to protect the HELF cells against BaP-induced loss in cell viability, achieving a maximum of 95.58% cell viability at the 0.5% concentration. Treatment of HELF cells with BaP alone significantly increased the level of Malondialdehyde (MDA) and decreased superoxide dismutase (SOD) and catalase (CAT). However, these effects were suppressed when the cells were also treated with LEO, leading to enhanced levels of SOD and CAT activities (2.9- and 2-fold, respectively, compared with BaP treatment only) and reduced the level of MDA in the cells (43% reduction in malondialdehyde level). At the same time, LEO also reduced the level of DNA damage, as shown by a reduced level of 8-hydroxy-deoxyguanosine (8-OHdG). Taken together, the results showed that LEO offered protection against BaP-induced OS and DNA damage, suggesting that LEO could be a promising agent for lung cancer chemoprevention.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"121 - 127"},"PeriodicalIF":3.2,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1266541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47173805","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}
Pub Date : 2017-01-25DOI: 10.1080/15376516.2016.1274351
Harikiran Lingabathula, N. Yellu
Abstract The study investigated the oxidative stress induction by the 10 and 25 nm silver nanorods (SNRs) following intra-tracheal instillation in rats after 1 day, 1 week, 1 month and 3 months post instillation periods at 1 and 5 mg/kg b.w. doses. The blood was withdrawn by retro orbital plexus method after exposure periods and different oxidative stress markers were estimated. The results showed that the both sizes of SNRs induced increased levels of malondialdehyde (MDA) and depleted glutathione (GSH) levels after 1 day and 1 week post exposure periods. The 10 and 25 nm SNRs at both doses displayed that significantly reduced levels of superoxide dismutase (SOD) and catalase following 1 day and 1 week post exposure periods. Also, the results have shown that decrease in total antioxidant capacity (TAC) of both sizes of SNRs significantly following 1 day and 1 week post exposure periods, indicating the oxidative stress induction by SNRs. In spite, there were no significant changes in oxidative stress markers following 1 month and 3 months post exposure periods may be due to recovery. The increased levels of MDA and decreased levels of GSH, SOD, catalase and TAC activity are strongly associated to ROS production and lipid peroxidation, suggesting the induction of oxidative stress in rats. The 10 nm SNRs at 5 mg/kg b.w. dose exposures in rats have shown greater changes in all oxidative stress parameters, indicating the greater induction of oxidative stress when compared with the 25 nm SNRs, representing the size–dose-dependent induction of oxidative stress of SNRs.
{"title":"Evaluation of oxidative stress induction in rats following exposure to silver nanorods","authors":"Harikiran Lingabathula, N. Yellu","doi":"10.1080/15376516.2016.1274351","DOIUrl":"https://doi.org/10.1080/15376516.2016.1274351","url":null,"abstract":"Abstract The study investigated the oxidative stress induction by the 10 and 25 nm silver nanorods (SNRs) following intra-tracheal instillation in rats after 1 day, 1 week, 1 month and 3 months post instillation periods at 1 and 5 mg/kg b.w. doses. The blood was withdrawn by retro orbital plexus method after exposure periods and different oxidative stress markers were estimated. The results showed that the both sizes of SNRs induced increased levels of malondialdehyde (MDA) and depleted glutathione (GSH) levels after 1 day and 1 week post exposure periods. The 10 and 25 nm SNRs at both doses displayed that significantly reduced levels of superoxide dismutase (SOD) and catalase following 1 day and 1 week post exposure periods. Also, the results have shown that decrease in total antioxidant capacity (TAC) of both sizes of SNRs significantly following 1 day and 1 week post exposure periods, indicating the oxidative stress induction by SNRs. In spite, there were no significant changes in oxidative stress markers following 1 month and 3 months post exposure periods may be due to recovery. The increased levels of MDA and decreased levels of GSH, SOD, catalase and TAC activity are strongly associated to ROS production and lipid peroxidation, suggesting the induction of oxidative stress in rats. The 10 nm SNRs at 5 mg/kg b.w. dose exposures in rats have shown greater changes in all oxidative stress parameters, indicating the greater induction of oxidative stress when compared with the 25 nm SNRs, representing the size–dose-dependent induction of oxidative stress of SNRs.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"272 - 278"},"PeriodicalIF":3.2,"publicationDate":"2017-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1274351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45656506","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}
Pub Date : 2017-01-24DOI: 10.1080/15376516.2017.1278812
Jin Yang, Ying Wang, Hui Liu, Ji-rui Bi, Youjin Lu
Abstract Noncardiogenic lung edema is a key factor affecting the prognosis of acute lung injury (ALI). Previous studies have been focused on regulatory roles of ceramide on lung vascular endothelial barrier functions and had already identified ceramide as mediator involved in the formation of lung edema. However, the effects of ceramide on lung epithelial barrier were still unknown. This study aimed to investigate the effects of ceramide on the barrier function of alveolar epithelial cells. Primary mouse alveolar type II epithelial cells (AECII) were grown on Transwell polyester membranes to construct monolayer, and stimulated with different concentrations of ceramide. Transepithelial resistance (TER) was measured to assess the epithelial cell permeability. Western blotting and real-time quantitative polymerase chain reaction were used to detect the mRNA and protein levels of tight junction, respectively. After incubation with different concentrations of c2-ceramide, TER of AECII monolayer decreased significantly in a dose-dependent manner. Moreover, expressions of ZO-1, occludin and claudin-4 were significantly reduced by c2-ceramide in the study. This study demonstrated that ceramide could increase alveolar epithelial cell monolayer permeability by downregulation of tight junction proteins. Therefore, modulation of ceramide expression may serve as a new therapeutic approach to treat acute lung injury.
{"title":"C2-ceramide influences alveolar epithelial barrier function by downregulating Zo-1, occludin and claudin-4 expression","authors":"Jin Yang, Ying Wang, Hui Liu, Ji-rui Bi, Youjin Lu","doi":"10.1080/15376516.2017.1278812","DOIUrl":"https://doi.org/10.1080/15376516.2017.1278812","url":null,"abstract":"Abstract Noncardiogenic lung edema is a key factor affecting the prognosis of acute lung injury (ALI). Previous studies have been focused on regulatory roles of ceramide on lung vascular endothelial barrier functions and had already identified ceramide as mediator involved in the formation of lung edema. However, the effects of ceramide on lung epithelial barrier were still unknown. This study aimed to investigate the effects of ceramide on the barrier function of alveolar epithelial cells. Primary mouse alveolar type II epithelial cells (AECII) were grown on Transwell polyester membranes to construct monolayer, and stimulated with different concentrations of ceramide. Transepithelial resistance (TER) was measured to assess the epithelial cell permeability. Western blotting and real-time quantitative polymerase chain reaction were used to detect the mRNA and protein levels of tight junction, respectively. After incubation with different concentrations of c2-ceramide, TER of AECII monolayer decreased significantly in a dose-dependent manner. Moreover, expressions of ZO-1, occludin and claudin-4 were significantly reduced by c2-ceramide in the study. This study demonstrated that ceramide could increase alveolar epithelial cell monolayer permeability by downregulation of tight junction proteins. Therefore, modulation of ceramide expression may serve as a new therapeutic approach to treat acute lung injury.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"293 - 297"},"PeriodicalIF":3.2,"publicationDate":"2017-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2017.1278812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44308750","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}
Pub Date : 2017-01-22DOI: 10.1080/15376516.2017.1279251
Yin He, Dehong Tan, B. Bai, Zhaoxia Wu, Shu-juan Ji
Abstract The potent neurotoxic agent acrylamide (ACR) is formed during Maillard reaction in food processing. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, is an antioxidant, but its effects on ACR-induced neurotoxicity are unclear. Here, we investigated the neuroprotective effects of EGCG against ACR-induced apoptosis and astrogliosis in the cerebral cortex. Rats were pretreated with EGCG for 4 d and then co-administered ACR for 14 d. Immunohistochemical analysis of glial fibrillary acidic protein and 8-hydroxy-2′-deoxyguanosine indicated that EGCG attenuated astrogliosis and DNA damage in ACR-treated rats. Analysis of DNA fragmentation and protein expression of Bax, Bcl-2, caspase 3, and cytochrome c revealed that EGCG inhibited ACR-induced apoptosis. Furthermore, EGCG inhibited oxidative stress by enhancing the activity of antioxidant enzymes and glutathione levels and reducing the formation of reactive oxygen species and lipid peroxidation. Taken together, our data demonstrate that EGCG inhibits ACR-induced apoptosis and astrogliosis in the cerebral cortex.
{"title":"Epigallocatechin-3-gallate attenuates acrylamide-induced apoptosis and astrogliosis in rat cerebral cortex","authors":"Yin He, Dehong Tan, B. Bai, Zhaoxia Wu, Shu-juan Ji","doi":"10.1080/15376516.2017.1279251","DOIUrl":"https://doi.org/10.1080/15376516.2017.1279251","url":null,"abstract":"Abstract The potent neurotoxic agent acrylamide (ACR) is formed during Maillard reaction in food processing. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, is an antioxidant, but its effects on ACR-induced neurotoxicity are unclear. Here, we investigated the neuroprotective effects of EGCG against ACR-induced apoptosis and astrogliosis in the cerebral cortex. Rats were pretreated with EGCG for 4 d and then co-administered ACR for 14 d. Immunohistochemical analysis of glial fibrillary acidic protein and 8-hydroxy-2′-deoxyguanosine indicated that EGCG attenuated astrogliosis and DNA damage in ACR-treated rats. Analysis of DNA fragmentation and protein expression of Bax, Bcl-2, caspase 3, and cytochrome c revealed that EGCG inhibited ACR-induced apoptosis. Furthermore, EGCG inhibited oxidative stress by enhancing the activity of antioxidant enzymes and glutathione levels and reducing the formation of reactive oxygen species and lipid peroxidation. Taken together, our data demonstrate that EGCG inhibits ACR-induced apoptosis and astrogliosis in the cerebral cortex.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"27 1","pages":"298 - 306"},"PeriodicalIF":3.2,"publicationDate":"2017-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2017.1279251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48322620","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}
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