共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid 总被引:3,自引:0,他引:3
Mirella Nardini E. I. Finkelstein S. Reddy G. Valacchi M. Traber C. E. Cross A. van der Vliet 《Toxicology》2002,170(3):173-185
Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system. 相似文献
3.
Marwan S.M. Al-Nimer Huda G. Hameed Majid M. Mahmood 《Saudi Pharmaceutical Journal》2015,23(5):483-486
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the growth of several cancer cell lines. The aim of this study is to compare the cytotoxic effect of aspirin with diclofenac on the growth of HeLa cell, mammary cell carcinoma, rhabdomyosarcoma and fibroblast cell lines in the culture media. The cells are cultured in RPMI-1640 culture media supplemented with 5% fetal calf serum and antibiotics. Aspirin (5 mg/well) and diclofenac (0.625 mg/well) significantly inhibit the growth of HeLa, rhabdomyosarcoma and fibroblast cells. The cytotoxic effect of aspirin against rhabdomyosarcoma is significantly (p < 0.001) higher than that of diclofenac with a potency approximated 2.6. It concludes that aspirin and diclofenac inhibit the growth of fibroblast and cancer cell by inhibiting the up-regulation of cyclooxygenases enzymes in cancer cells. Aspirin is more effective than diclofenac against the growth of rhabdomyosarcoma cell line. 相似文献
4.
目的体外诱导成人骨髓间充质干细胞(MSCs)向神经元样细胞分化,并探讨分化过程中多效蛋白(PTN)mRNA的表达,以了解MSCs向神经元样细胞分化的特性和机制。方法密度梯度离心加贴壁培养法分离成人MSCs,原代和传代培养。取第6代MSCs设对照和试验组进行诱导,诱导后30 min至3 d,观察细胞形态并计数。免疫细胞化学法和反转录-聚合酶链反应(RT-PCR)法测定分化后细胞神经细胞特异性表面标志神经元烯醇化酶(NSE)、微管相关蛋白(MAP)-2,胶原酸性蛋白(GFAP)和诱导前、诱导后12 h PTN mRNA的表达。结果接种24 h后MSCs开始贴壁,呈圆形或椭圆形。3 d后可见梭状细胞呈集落状生长,10~14 d融合。第5~6代时呈现较均一的成纤维细胞样形态。诱导后胞体向胞核收缩;出现双极及多极细胞。12 h变形细胞增多,细长突起相互连接。24 h后变形细胞增多不明显。诱导后12 h大部分细胞表达NSE(64.79±0.07)%、MAP-2(60.05±0.09)%,未检测到GFAP的表达,RT-PCR半定量检测有NSE mRNA的表达(0.66±0.15)。实验组诱导后12 h细胞有PTN mRNA的表达(0.689±0.017)。结论建立了稳定的成人MSCs培养增殖体系,MSCs可体外诱导分化为神经元样细胞,在分化过程中有外观形态变化和特异性标志物NSE和MAP-2的表达,同时有PTN mRNA的表达,提示PTN可能参与调控了MSCs向神经元样细胞的分化。 相似文献
5.
《Inhalation toxicology》2013,25(2):118-125
AbstractSmog inhalation is associated with acute respiratory symptoms in exposed victims. However, despite the evidence from cell injury caused by smog, a stable and practical apparatus used to treat cells with smog is necessary. The aim of this study is to develop a cell research platform of smoke inhalation injury. In the smog-generation device, a wireless electromagnetic heater was used to ignite gunpowder and generate smog. The quality of black powder was checked by the black powder burn rate, and experimental smog was indirectly checked by the amount of cell damage. The temperature and humidity were set at 37?°C?±?1?°C and ≥95% in the smog-cells reaction chamber, respectively. Factors including gunpowder dosages, smog-exposure time, the cell density, modes of exposure, volumes of smog, test durations, volumes of the cell culture medium and combustion velocity were measured. Coefficient variation of different batches of gunpowder and smog were less than 4% and 9%, respectively. With larger gunpowder dosage and longer exposure time, cell injury appeared to increase. When cells were cultured in 4?×?104/well density in culture medium (1?mL/well), exposed to more than 10?L smog with filter screens above plates, detected after 24?h culture in cell incubator and gunpowder burned out within 5?s, smog had the best effect on cell injury. In conclusion, the experimental device can produce test smog stably and safely. The apparatus treating cells with smog can induce cell injury effectively, and the injury is positively correlated with smog concentration and exposure time. 相似文献
6.
The cytotoxicity of 15-nm and 46-nm silica nanoparticles was investigated by using crystalline silica (Min-U-Sil 5) as a positive control in cultured human bronchoalveolar carcinoma-derived cells. Exposure to 15-nm or 46-nm SiO(2) nanoparticles for 48 h at dosage levels between 10 and 100 microg/ml decreased cell viability in a dose-dependent manner. Both SiO(2) nanoparticles were more cytotoxic than Min-U-Sil 5; however, the cytotoxicities of 15-nm and 46-nm silica nanoparticles were not significantly different. The 15-nm SiO(2) nanoparticles were used to determine time-dependent cytotoxicity and oxidative stress responses. Cell viability decreased significantly as a function of both nanoparticle dosage (10-100 microg/ml) and exposure time (24 h, 48 h, and 72 h). Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species (ROS), glutathione, malondialdehyde, and lactate dehydrogenase, were quantitatively assessed. Exposure to SiO(2) nanoparticles increased ROS levels and reduced glutathione levels. The increased production of malondialdehyde and lactate dehydrogenase release from the cells indicated lipid peroxidation and membrane damage. In summary, exposure to SiO(2) nanoparticles results in a dose-dependent cytotoxicity in cultural human bronchoalveolar carcinoma-derived cells that is closely correlated to increased oxidative stress. 相似文献
7.
Sato H Nave R Nonaka T Mochizuki T Takahama S Kondo S 《Biopharmaceutics & drug disposition》2007,28(1):43-50
Ciclesonide, a corticosteroid in development for allergic rhinitis, is converted to the pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC), and des-CIC is subsequently esterified with fatty acids. Various experiments were performed to investigate ciclesonide metabolism in human nasal epithelial cells (HNEC). Human nasal epithelial cells were incubated with (a) 0.1 microM ciclesonide for 1 h and medium without ciclesonide for up to 24 h, (b) esterase inhibitors for 0.5 h followed by 5 microM ciclesonide for 6 h, or (c) 1 microM des-CIC for 6 h followed by medium without des-CIC for up to 24 h. Ciclesonide, des-CIC and des-CIC fatty acid conjugate concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. The amount of ciclesonide in HNEC decreased approximately 93-fold from 0.5 to 24 h. In contrast, des-CIC was present at constant levels throughout the post-treatment period. Furthermore, fatty acid conjugates of des-CIC were retained in HNEC up to 24 h post-treatment. Carboxylesterase and cholinesterase inhibitors decreased ciclesonide metabolism > or =50%. The total amounts of des-CIC fatty acid conjugates decreased and the extracellular amounts of des-CIC increased with time. In conclusion, ciclesonide was rapidly converted to des-CIC by carboxylesterases and cholinesterases, and des-CIC underwent reversible fatty acid conjugation in HNEC. 相似文献
8.
Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure 总被引:1,自引:0,他引:1
Corsini E Codecà I Mangiaratti S Birindelli S Minoia C Turci R Viviani B Facchi A Vitelli N Lucchi L Galli CL Marinovich M Colosio C 《Toxicology and applied pharmacology》2007,222(2):202-210
9.
Rachel J. Person Erik J. TokarYuanyuan Xu Ruben OrihuelaNtube N. Olive Ngalame Michael P. Waalkes 《Toxicology and applied pharmacology》2013
Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. 相似文献
10.
利用原代大鼠气管上皮(RTE)细胞研究N-甲基-N′-硝基-N-亚硝基胍(MNNG)的致转化作用,并对转化细胞进行细胞遗传学研究. 结果表明:增殖旺盛细胞(EGV)集落是RTE细胞体外转化最早期的特征,EGV转化频率与MNNG剂量呈明显的剂量反应关系. 从0.3 mg·L-1 MNNG剂量组分离到2个EGV集落,经消化,传代形成了永生化的细胞系(RTES1,RTES2),RTES1为多倍体核型,2号和7号染色体数目增加至4个且呈高频发生(100%); RTES2呈二倍体核型. 电镜结果证实转化细胞来自大鼠气管上皮组织. 以上结果提示,原代RTE细胞体外培养模型是研究致癌物定量及致癌机理的理想模型系统. 相似文献
11.
He Wang Hong Zhou Cheng-Xi Wang Yue-Shan Li Hong-Yan Xie Jian-Dong Luo Yi Zhou 《Food and chemical toxicology》2012
The aim of the therapy of human malignancies is the inhibition of cell proliferation and/or induction of apoptosis. In present experiment, we investigated the in vitro and in vivo anticancer effects and associated mechanisms of paeoniflorin (PF), isolated from the paeony root, against colorectal cancer. In vitro, cell growth assay obviously showed the inhibition of tumor cell growth in a dose-dependent manner. Flow cytometry analysis showed that PF could mainly have the cell cycle arrest at G1, which is associated with DNA damage and activation of p53/14-3-3 zeta (ζ). The pro-apoptotic effect of PF was demonstrated by Annexin V-PI staining, and activation of caspase-3 and caspase-9 by Western immunoblotting. In vivo, the results showed that positive cells of PCNA in PF and docetaxel-treated group was decreased to 30% and 15% compared with control group of tumors, respectively. But apoptosis cells in PF- and docetaxel treated groups studied by TUNEL is increased to 40 ± 1.2% and 30 ± 1.5% compared with 24 ± 2.3% in negative control, respectively. Furthermore, the efficiency of tumor-bearing mice treated by PF was superior to docetaxel in vivo. Overall, PF may be an effective chemopreventive agent against colorectal cancer HT29, and the mechanism could be mediated via an regulation of p53/14-3-3ζ. 相似文献
12.
《Journal of applied toxicology : JAT》2017,37(6):747-757
People are taking up antioxidants in their daily diet and being exposed to a potential diesel exhaust particles (DEP)‐containing environment. Thus it is important to study in vitro cellular responses when cells are exposed to DEP with or without antioxidant treatment. The investigation of DEP and resveratrol (RES) on cellular biophysical and biochemical changes is needed to better understand the mechanisms of DEP and RES in mammalian cells. A combination of two non‐invasive techniques (atomic force microscopy, AFM, and Raman spectroscopy, RM) and multimodal tools were applied to evaluate the biophysical, biochemical alterations and cytokine, membrane potential and cell cycle of cells with or without RES pretreatment to different times of DEP exposure. AFM results indicated that RES protected cells from DEP‐induced damage to cytoskeleton and cell architectures, and noted that RES treatments also attenuated DEP‐induced alterations in cell elasticity and surface adhesion force over DEP incubation time. RM monitored the changes in characteristic Raman peak intensities of DNA and protein over the DEP exposure time for both RES and non‐RES treated groups. The cytokine and chemokine changes quantified by Multiplex ELISA revealed that the inflammatory responses were enhanced with the increase in DEP exposure time and that RES enhanced the expression levels of cytokine and chemokine. This work demonstrated that significant biophysical and biochemical changes in cells might be relevant to early pathological changes induced by DEP damage. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
13.
目的应用噬菌体随机肽库技术筛选出与肺癌细胞特异性结合的多肽。方法以人肺癌细胞NCI-H1299为靶细胞,人胚肺细胞MRC-5为吸附细胞,对噬菌体随机12肽库进行3轮全细胞减性筛选后,随机挑取噬菌体克隆进行ELISA鉴定;对亲和力较高的阳性克隆进行DNA测序并翻译为氨基酸序列;化学合成异硫氰酸荧光素标记的多肽(FITC-ZS-5),采用细胞和组织免疫荧光法鉴定FITC-ZS-5与肺癌细胞的亲和力及特异性。结果通过3轮减性筛选后,与NCI-H1299细胞结合的噬菌体克隆得到有效的富集;ELISA结果显示5号克隆对NCI-H1299细胞亲和力最高,将其命名为Phage ZS-5;测序结果显示Phage ZS-5所表达的多肽序列在国内外均未见报道,细胞及组织免疫荧光实验结果显示FITC-ZS-5对肺癌细胞及组织具有较高的亲和力和特异性。结论应用噬菌体随机肽库技术筛选到肺癌靶向性多肽ZS-5,为肺癌的靶向治疗和诊断奠定基础。 相似文献
14.
Sang-Woo Lee Jae-Tae Lee Maan-Gee Lee Ho Won Lee Sohn Joo Ahn Yong Jin Lee You La Lee Jeongsoo Yoo Byeong-Cheol Ahn Jeoung-Hee Ha 《Journal of natural medicines》2009,63(2):124-129
The need for beneficial use of sedatives in oncologic patients is increasing. Therefore, in this study, antiproliferative
characteristics of herbal and synthetic sedatives were examined in vitro in SNU-C4 human colorectal adenocarcinoma cells.
Apigenin (50% inhibition concentration, IC50 = 1.8 ± 0.5 μM) and diazepam (IC50 = 7.0 ± 0.5 μM) showed concentration-dependent inhibition of SNU-C4 cancer cell survival. Efficacy of cancer cell survival
inhibition by apigenin and diazepam was much lower than that of 5-fluorouracil (5-FU), a known chemotherapeutic drug. However,
10−6 M concentration of apigenin and diazepam potentiated 5-FU-induced cytotoxicity. In SNU-C4 cells, 10−6 M concentrations of diazepam, flumazenil (Ro15-1788), Ro5-4864, or PK11195, all ligands for central- or peripheral-type benzodiazepine
(BZD) receptors, inhibited cell survival like the flavonoid apigenin (4′,5,7-trihydroxyflavone) and fisetin (3,7,3′,4′-tetrahydroxyflavone).
Also like the plant flavonoids, treatment with 10−6 M concentration of diazepam for 3 days hardly affect the peripheral-type BZD receptor (PBR) messenger RNA (mRNA) expression
and inhibited glucose utilization of SNU-C4 cells. Treatment with flavonoids or diazepam for 6 days upregulated PBR mRNA expression
and cell cytotoxicity of SNU-C4 cells. Furthermore, treatment with 10−6 M concentration of apigenin, a natural sedative material originating from traditional herbs, positively modulated BZD-induced
antiproliferative cytotoxicity in SNU-C4 cells. Overall, the in vitro antiproliferative activity on SNU-C4 cancer cells of
herbal sedatives, such as apigenin, plus additive enhancement of synthetic BZD- and 5-FU-induced antiproliferative activities,
were shown. In conclusion, this study provides experimental basis for advanced trial in the future. 相似文献
15.
《Nanotoxicology》2013,7(2):148-161
AbstractWhile production of engineered carbon nanotubes (CNTs) has escalated in recent years, knowledge of risk associated with exposure to these materials remains unclear. We report on the cytotoxicity of four CNT variants in human lung epithelial cells (A549) and murine macrophages (J774). Morphology, metal content, aggregation/agglomeration state, pore volume, surface area and modifications were determined for the pristine and oxidized single-walled (SW) and multi-walled (MW) CNTs. Cytotoxicity was evaluated by cellular ATP content, BrdU incorporation, lactate dehydrogenase (LDH) release, and CellTiter-Blue (CTB) reduction assays. All CNTs were more cytotoxic than respirable TiO2 and SiO2 reference particles. Oxidation of CNTs removed most metallic impurities but introduced surface polar functionalities. Although slopes of fold changes for cytotoxicity endpoints were steeper with J774 compared to A549 cells, CNT cytotoxicity ranking in both cell types was assay-dependent. Based on CTB reduction and BrdU incorporation, the cytotoxicity of the polar oxidized CNTs was higher compared to the pristine CNTs. In contrast, pristine CNTs were more cytotoxic than oxidized CNTs when assessed for cellular ATP and LDH. Correlation analyses between CNTs’ physico–chemical properties and average relative potency revealed the impact of metal content and surface area on the potency values estimated using ATP and LDH assays, while surface polarity affected the potency values estimated from CTB and BrdU assays. We show that in order to reliably estimate the risk posed by these materials, in vitro toxicity assessment of CNTs should be conducted with well characterized materials, in multiple cellular models using several cytotoxicity assays that report on distinct cellular processes. 相似文献
16.
Mingjie Tang Qifei Li Lifu Xiao Yanping Li Judy L. Jensen Theodore G. Liou Anhong Zhou 《Toxicology letters》2012
In this study, confocal Raman spectroscopy, atomic force microscope (AFM) and multiplex ELISA were applied to analyze the biophysical responses (biomechanics and biospectroscopy) of normal human primary small airway epithelial cells (SAECs) and human lung carcinoma epithelial A549 cells to in vitro short term DEP exposure (up to 2 h). Raman spectra revealed the specific cellular biomolecular changes in cells induced by DEP compared to unexposed control cells. Principal component analysis was successfully applied to analyze spectral differences between control and treated groups from multiple individual cells, and indicated that cell nuclei are more sensitive than other cell locations. AFM measurements indicated that 2 h of DEP exposure induced a significant decrease in cell elasticity and a dramatic change in membrane surface adhesion force. Cytokine and chemokine production measured by multiplex ELISA demonstrated DEP-induced inflammatory responses in both cell types. 相似文献
17.
In the present study, in vitro cytotoxic and genotoxic effect of copper–zinc alloy nanoparticles (Cu–Zn ANPs) on human lung epithelial cells (BEAS-2B) were investigated. XTT test and clonogenic assay were used to determine cytotoxic effects. Cell death mode and intracellular reactive oxygen species formations were analyzed using M30, M65 and ROS Elisa assays. Genotoxic effects were evaluated using micronucleus, comet and γ-H2AX foci assays. Cu–Zn ANPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurements. Characterization of Cu–Zn ANPs showed an average size of 200 nm and zeta potential of −22 mV. TEM analyses further revealed the intracellular localization of Cu–Zn ANPs in cytoplasm within 24 h. Analysis of micronucleus, comet and γ-H2AX foci counts showed that exposure to Cu–Zn ANPs significantly induced chromosomal damage as well as single and double stranded DNA damage in BEAS-2B cells. Our results further indicated that exposure to Cu–Zn ANPs significantly induced intracellular ROS formation. Evaluation of M30:M65 ratios suggested that cell death was predominantly due to necrosis. 相似文献
18.
Ozgur Esim Nurgul K. Bakirhan Nuray Yildirim Meral Sarper Ayhan Savaser Sibel A. Ozkan Yalcin Ozkan 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2020,28(2):673
BackgroundPlatinum-based chemotherapy in non-small cell lung cancer (NSCLC) has been demonstrated as a promising approach by many researchers. However, due to low bioavailability and several side effects, drug targeting to lungs by intravenous administration is not a common route of administration.ObjectiveIn this study, oxaliplatin loaded polycaprolactone (PCL) nanoparticles were prepared to overcome the limitations of the drug. 33 factorial design was used to evaluate the combined effect of the selected variables on the nanoparticle characteristics and to optimize oxaliplatin loaded PCL nanoparticles.MethodsThe factorial design was used to study the influence of three different independent variables on the response of nanoparticle particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. The cellular uptakes of oxaliplatin loaded nanoparticles with different molecular weights of PCL were evaluated. Moreover, optimized nanoparticles were evaluated for their efficacy in non-small lung cancer using the SK-MES-1 cell line.ResultsIn factorial design, it is found that the homogenization speed and surfactant ratio represented the main factors influencing particle size and PDI and did not seem to depend on the PCL ratio. While the cytotoxicity of free oxaliplatin and oxaliplatin loaded nanoparticles were similar in low drug doses (2.5 and 25 μg/mL), the cytotoxicity of oxaliplatin loaded nanoparticles on SK-MES-1 cell was found higher in higher doses (p < 0.05). Moreover, oxaliplatin nanoparticles formulated with different molecular weights of PCL did not show significant differences in cellular uptake in 1 h and 2 h. However, the uptake of PCL80000 NPs was found significantly greater than free oxaliplatin at 4 h (p < 0.05).ConclusionHence, the development of oxaliplatin loaded PCL nanoparticles can be a useful approach for effective NSCLC therapy.Graphical abstract Open in a separate windowDevelopment, optimization and in vitro evaluation of oxaliplatin loaded nanoparticles in non-small cell lung cancer 相似文献
19.
Riganti C Aldieri E Bergandi L Tomatis M Fenoglio I Costamagna C Fubini B Bosia A Ghigo D 《Toxicology and applied pharmacology》2003,193(1):106-115
The mechanism by which asbestos fibers are fibrogenic and tumorigenic is still matter of debate. The higher pathogenicity of longer fibers has been traditionally associated with their slower clearance in respiratory airways. However, short amosite fibers, obtained by grinding longer ones, exhibited a lower potential to damage nude DNA and a lower in vitro cytotoxicity. We have thus revisited the two sets of long and short fibers in order to compare their surface properties to their activity in cell systems. In this study we report that, in human lung epithelial cells A549, long amosite fibers, more effectively than the short ones, initiate free radical reactions, inhibit the glucose 6-phosphate dehydrogenase activity and the pentose phosphate pathway, decrease the intracellular level of reduced glutathione, and increase the generation of thiobarbituric acid reactive substances and the leakage of lactate dehydrogenase in the extracellular medium. These results suggest that the shortening of fibers by prolonged milling affects not only their biopersistence, but also their surface properties, hence their interaction with cellular metabolism. Our data provide also a mechanism by which asbestos fibers inhibit the pentose phosphate pathway, i.e., via the oxidative inhibition of glucose 6-phosphate dehydrogenase, which is prevented by reduced glutathione. 相似文献