金雀异黄酮对同型半胱氨酸诱导的内皮细胞氧化损伤的保护作用

背景与目的:探讨同型半胱氨酸(homocysteine,HCY)诱导的人脐静脉内皮细胞株ECV-304的氧化应激损伤及金雀异黄酮(genistein,GEN)对这种损伤的保护作用.材料与方法:以5.0 mmol/L的HCY作用于ECV-304细胞;同时设不同浓度的GEN(10、50、100 μmol/L)保护组,各保护组预先加入GEN孵育12 h后,再加入5.0 mmol/L的HCY.通过四噻氮唑盐(MTT)比色法观察细胞活性,使用流式细胞术检测胞浆活性氧(ROS)水平. 结果:HCY可降低ECV-304细胞的细胞活力,HCY处理后的细胞ROS水平与对照组相比明显升高(P<0.01);经不同浓度的GEN预处理后,细胞活性较单独HCY处理组显著增高(P<0.05),而50和100 μmol/L GEN处理组ROS水平较单独HCY处理组显著降低(P<0.05),且呈现剂量依赖性.结论:HCY可使ECV-304细胞氧化应激损伤,活力下降,而GEN具有抗氧化作用,能降低内皮细胞氧化损伤的程度.     

3-氯-4-二氯甲基-5-羟基-2(5氢)-呋喃酮对小鼠的遗传毒性与氧化损伤的关系

背景与目的：研究饮水氯化消毒副产物3-氯-4-二氯甲基-5-羟基-2(5氢)-呋喃酮(3-chloro-4-(dichlommethyl)-5-hydroxy-2[5H]-furanone,MX)对小鼠的遗传毒性与氧化损伤的诱导。材料与方法：昆明种小鼠随机分为4组,即溶剂对照组与低、中、高3个MX剂量组(11、33、100mg／kg),受试小鼠经腹腔注射染毒3h后处死。应用单细胞凝胶电泳技术(SCGE,彗星分析)检测小鼠肝、肾、小肠的DNA损伤,并测定小鼠肝、肾和小肠中脂质过氧化主要终产物丙二醛(Malondialdehyde,MDA)的含量。结果：随着MX浓度的增加,小鼠肝、肾、小肠中MDA含量与其细胞的Olive尾矩明显升高,且呈现较好的剂量依赖性。与溶剂对照组比较：①MX各剂量组小肠细胞Olive尾距均显著性增加,肝、肾细胞的Olive尾距在MX较高剂量时有显著性增加;②中、高剂量组小鼠肝组织中MDA含量显著性升高,高剂量组小鼠肾和小肠组织中MDA含量明显升高,差异有显著性意义。肝、肾、小肠MDA含量与Olive尾矩均呈明显正相关。结论：MX可引发哺乳动物多种脏器的脂质过氧化反应增强;并能引起细胞DNA损伤。MX导致机体组织的氧化损伤可能在细胞遗传毒性作用中起重要作用。     

三丁基锡引起人羊膜细胞氧化损伤及DNA损伤的研究

背景与目的： 研究三丁基锡 (tributyltin,TBT)对人羊膜细胞FL (human amnion cells) 氧化损伤和DNA损伤的诱导作用。 材料与方法： 将不同浓度TBT (0、2、4、6、8、10 μmol/L),分别对FL染毒2 h和4 h,各染毒组同时设不加TBT的对照组,染毒后分别用MTT法检测TBT对FL细胞增殖率的影响,用DCFH_DA法检测FL细胞活性氧自由基 (ROS)水平,用彗星实验检测TBT对FL细胞DNA的损伤。 结果： TBT对FL细胞染毒4 h时,其2、8、10 μmol/L浓度组的细胞增殖率较对照组显著下降(P<0.05,P<0.01,P<0.001),且随TBT浓度升高而增殖率呈下降的趋势。TBT 3、4 μmol/L染毒组FL细胞的ROS水平较对照组升高,且4 μmol/L染毒组与对照组比较差异具有统计学意义(P<0.05)。在TBT 2、3、4 μmol/L染毒组随着TBT浓度的升高,FL细胞核尾长、尾相均显著升高(P均<0.05)。 结论： TBT可引起FL细胞的氧化损伤及DNA损伤。     

烹调油烟颗粒物对HELF细胞的氧化应激效应研究

背景与目的:探讨烹调油烟颗粒物(cooking oil fume particulate,COFP)对人胚肺二倍体成纤维细胞(human embryonic diploid lung fibroblasts,HELF)的氧化应激效应.材料与方法:用玻璃纤维滤膜采集烹调油烟颗粒物,通过MTY实验确定COFP暴露对HELF细胞的lC50.将HELF细胞暴露于20、4、0.8 μg/ml的COFP,分别于12、24、48 h后进行活性氧(reactive oxygen species,Ros)分析、丙二醛(malondialdehyde,MDA)检测和彗星试验(comet assay).结果:COFP作用12、24、48 h后HELF细胞的IC50分别是101.7、82.7、85.1 μg/ml,细胞质内ROS平均荧光强度随COFP剂量增加而增高,在COFP 0.8、4 μg/ml暴露24、48 h后线粒体内的ROS较阴性对照组升高,其差异具有统计学意义(P＜0.05).实验组MDA水平与阴性对照组相比差异无统计学意义(P＞0.05).实验组DNA断裂水平与阴性对照组相比,差异有统计学意义(P＜0.05).各实验组引起的细胞ROS、MDA升高和DNA断裂在不同暴露时间之间差别均无统计学意义(P＞0.05).结论:在实验剂量水平和暴露时间内,COFP暴露可引起HELF细胞胞质和线粒体内ROS升高、DNA断裂,但并不能引起脂质过氧化损伤.     

The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO₃) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO₃ i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO₃ i.p. treatment, which itself caused no change. Administration of KBrO₃ itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO₃ lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO₃ were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO₃.     

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

The protective effect of aG-Rutin against ferric nitrilotriacetate (Fe-NTA)-induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of αG-Rutin (50 μmol as rut in/leg) by gastric intubation 30 min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg FeAg/day for the first 3 days and 3 mg Fe/ kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given αG-Rutin 30 min after each Fe-NTA treatment. To elucidate the mechanism of protection by αG-Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of αG-Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-l-pyrroline-N-oxide (DMPO), respectively. When mice were given αG-Rutin (50 μmol as rutin Ag) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of äG-Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min. äG-Rutin inhibited the formation of DMPO-OH in a concentration-dependent manner. Further, chelating activity of äG-Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed äG-Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe-NTA.     

Inhibition of Oxidative Stress and Enhancement of Cellular Activity by Mushroom Lectins in Arsenic Induced Carcinogenesis

Chronic arsenicosis is a major environmental health hazard throughout the world, including India. Animals and human beings are affected due to drinking of arsenic contaminated ground water, due to natural mineral deposits, arsenical pesticides or improperly disposed arsenical chemicals. Arsenic causes cancer with production of free radicals and reactive oxygen species (ROS) that are neutralized by an elaborate antioxidant defense system consisting of enzymes and numerous non-enzymatic antioxidants. Dietary antioxidant supplements are useful to counteract the carcinogenesis effects of arsenic. Oyster mushroom lectins can be regarded as ingredients of popular foods with biopharmaceutical properties. A variety of compounds have been isolated from mushrooms, which include polysaccharides and polysaccharopeptides with immune-enhancing effects. Lectins are beneficial in reducing arsenic toxicity due to anticarcinogenetic roles and may have therapeutic application in people suffering from chronic exposure to arsenic from natural sources, a global problem that is especially relevant to millions of people on the Indian subcontinent.     

修复基因MTH1与OGG1在H_2O_2诱导的DNA氧化性损伤中的作用研究

背景与目的:利用H202作用于11型人肺泡上皮细胞A549,分析8-羟基脱氧鸟苷(8-oxo-dG)的形成,探讨修复基因hMTH1与hOGG1在DNA氧化性损伤中的作用.材料与方法:在A549细胞培养液中分别加入终浓度为0、50、100、200和300 μmol/L的H202孵育不同时间(0、6、12、18和24 h)后,利用高压液相色谱串联电化学检测技术、核酸内切酶切割法及RT-PCR技术分析细胞8-oxo-dG水平、8-oxo-dG修复酶活性及hOGG1和hMTH1基因表达水平.结果:与对照组比较,100、200、300 μmol/L H202 浓度时均能使A549细胞DNA的8-oxo-dG水平增高(P<0.05或P相似文献   

Chemoprevention by Triticum Aestivum of Mouse Skin Carcinogenesis Induced by DMBA and Croton Oil - Association with Oxidative Status

Chemopreventive action of wheat grass (Triticum astivum) leaf extract in Swiss albino mice was evaluated.Oral administration of wheat grass leaf extract at a dose level of 20 ml/kg body weight per day at pre, peri, andpost-initional phases and in combination group, caused significant variation in tumour incidence and tumouryield as compared to the control group. Moreover, the average latent period was significantly increased from9.87±0.12 to 13.4±0.23 weeks in the combination group, together with significant elevation of reduced glutathione(GSH), superoxide dismutase (SOD) catalase (CAT) and reduction in lipid peroxidation (LPO) was observed ascompared to the control group.     

H.Pylori感染后氧化应激损伤与胃癌关系的研究进展

本文介绍了H.Pylori感染后，可通过两个途径产生活性氧和活性氮自由基，总结了这两类自由基所致机体产生氧化应激损伤的特点，以及机体参与抗氧化损伤系统的酶，如MnSOD、CAT`GPX活性与H.Pylori感染、胃癌和癌前病变之间的关系，同时，对研究领域尚存在的问题和今后的研究方向进行了展望。     

运用单细胞凝胶电泳研究稀土元素钬对小鼠骨髓细胞DNA的损伤

背景与目的:探讨稀土元素钬对小鼠骨髓细胞DNA的损伤.材料与方法:给小鼠灌胃氧化钬的盐酸溶液,24h后取股骨骨髓细胞进行单细胞凝胶电泳,观察有无染色体损伤和DNA损伤.结果:试验表明在20～80 mg/kg剂量范围内,彗星细胞的尾长随剂量的增加而增长,而头长则随剂量的递增而缩短,并且在40～80 mg/kg剂量范围内与阴性组差异存在显著性;同时,拖尾率与DNA损伤率也随剂量的增加而升高.结论:稀土元素钬对小鼠骨髓细胞DNA具有一定的损伤作用.     

Amelioration of 1,2 Dimethylhydrazine (DMH) Induced Colon Oxidative Stress,Inflammation and Tumor Promotion Response by Tannic Acid in Wistar Rats

Colon cancer is the third most common malignant neoplasm in the world and it remains an important causeof death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), isalso a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemicallyinduced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TAagainst DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated interms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changesand expression of early molecular markers of inflammation and tumor promotion. DMH treatment inducedoxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons ofWistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanismthat involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-α(p<0.001) release. It could be concluded from our results that TA markedly protects against chemically inducedcolon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.     

The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress,Inflammation and Proliferation in Rat Liver,Stomach and Colon: Protective Effect of Ginger Extract

Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of variousorgans. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENAin different organs namely, liver, stomach and colon and the potential protective effect of GE against these mechanisms.Methods: Adult male albino rats were assigned into four groups. A normal control group received the vehicle, anothergroup was injected with a single necrogenic dose of DENA (200 mg/kg, i.p) on day 21. Two groups received oral GE(108 or 216 mg/kg) daily for 28 days. Sera, liver, stomach and colon were obtained 7 days after DENA injection. Serumaspartate transaminase and alanine transaminase were detected as well as reduced glutathione (GSH), malondialdehyde,nitric oxide metabolites, interleukin 1β, tumor necrosis factor (TNF-α), alpha-fetoprotein (AFP) and nuclear factorerythroid2-related factor2 (Nrf2) in liver, stomach and colon. Histopathological studies and immunohistochemicalexamination of cyclooxygenase-2 (COX2) were conducted. Results: DENA induced elevation in liver function enzymeswith significant increase in oxidation and inflammation biomarkers and AFP while decreased levels of Nrf2 in liver,stomach and colon were detected. Histologically, DENA showed degenerative changes in hepatocytes and inflammatoryfoci. Inflammatory foci displayed increased expression of COX2 in immunohistochemical staining. GE-pretreatmentimproved liver function and restored normal GSH with significant mitigation of oxidative stress and inflammatorybiomarkers compared to DENA-treated group. AFP was reduced by GE in both doses, while Nrf2 increased significantly.Histology and immunostaining of hepatic COX-2 were remarkably improved in GE-treated groups in a dose dependentmanner. Conclusion: GE exerted a potential anti-proliferative activity against DENA in liver, stomach and colon viaNrf2 activation, whilst suppression of oxidation and inflammation.     

Protection of Survival and Hematopoiesis in Irradiated Mice by 5-FIuorouracil

The effects of whole-body irradiation on survival and the hematopoietic system were studied in mice treated with 5-fluorouracil (5-FU). Animals (ddY-SLC male mice, 8–10 weeks old) were injected with 5-FU (i.p.) as a single dose (150 mg/kg) at various times before or after irradiation with X-rays at graded doses (4.8 to 7.6 Gy). The treatment of mice with 5-FU 5 days before irradiation was the most effective for the reduction of radiation lethality, having a radioprotective effect. The dose reduction factor (DRF) was 1.24. However, treatment with 5-FU at 1 day and 2 hours before, or at various times after irradiation significantly increased the radiation lethality compared to the untreated controls, creating a radiosensitizing effect. The decrease or the increase of radiation lethality exhibited by 5-FU was similar to. the radiation-dose relationship pattern shown by endogenous and exogenous CFU-S. The pattern of change of thrombocyte counts in the circulating blood after irradiation was greatly modified by pretreatment with 5-FU 5 days before irradiation, effectively lessening the radiation-induced depression. In contrast, the post-irradiation patterns of leukocyte and erythrocyte variation did not show any significant change due to pretreatment with 5-FU.     

不良心理应激对人卵巢癌裸鼠血清sIL-2R、VEGF和CA125的影响

目的探讨不良心理应激对人卵巢上皮性癌荷瘤裸鼠血清可溶性白介素2受体（sIL-2R）、血管内皮生长因子（VEGF)和CA125影响。方法将24只裸鼠随机分为4组：正常生长组（Ⅰ）、单纯应激组（Ⅱ）、单纯荷瘤组（Ⅲ）、荷瘤+应激组（Ⅳ）,每组6只,建立相应的人卵巢上皮性癌荷瘤裸鼠模型和不良心理应激模型。观察皮下瘤生长情况、裸鼠体重的变化,采用酶联免疫吸附法（ELISA）检测各组裸鼠血清中sIL-2R、CA125、VEGF的含量。结果Ⅳ组裸鼠皮下瘤比Ⅲ组生长较快,肿瘤增长率达66.33%。Ⅱ组裸鼠血清中sIL-2R、VEGF水平与Ⅰ组相比,差异有统计学意义（P<0.05）,sIL-2R、VEGF水平明显高于对照组（P<0.05）;Ⅱ组裸鼠血清中CA125水平与Ⅰ组相比差异无统计学意义（P>0.05）。Ⅲ组与Ⅰ组,Ⅳ组与Ⅰ组相比sIL-2R、VEGF、CA125水平均差异有统计学意义（P<0.05）。结论不良心理应激可抑制荷瘤裸鼠的免疫功能,导致肿瘤快速增长。     

Chemoprevention by Butea Monosperma of Hepatic Carcinogenesis and Oxidative Damage in Male Wistar Rats

In this communication, we document chemopreventive effects of Butea monosperma extract on hepatic ‍carcinogenesis and on tumor promoter induced markers and oxidative stress in male Wistar rats. Treatment of male ‍Wistar rats for five consecutive days with 2-AAF i.p. induced significant hepatic toxicity, oxidative stress and ‍hyperproliferation. Pretreatment of B.monosperma extract (100 and 200 mg/kg body weight) prevented oxidative ‍stress by restoring the levels of antioxidant enzymes and also prevented toxicity at both doses. The promotion ‍parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF administration in diet with ‍partial hepatectomy (PH) were also significantly suppressed dose dependently by B. monosperma. Thereafter, we ‍proceeded with studies on rat liver carcinogenesis. After fourteen days of DEN treatment, dietary administration of ‍2-AAF with PH resulted in a 100% incidence of tumors in the animals. However, B.monosperma caused reduction in ‍the number of tumors/ rat and percentage of tumor bearing rats at the end of the study, as confirmed histologically. ‍Thus, our data suggest that B.monosperma extract is a potent chemopreventive agent which suppresses 2-AAFinduced ‍hepatic carcinogenesis and oxidative damage in Wistar rats. The protective activity of the plant might be ‍due to the two major constituents (butrin and isobutrin).     

Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.     

硫普罗宁对放疗所致小鼠白细胞减少的预防及治疗作用

为观察硫普罗宁 (Tiopronin ,MPG)对放疗所致小鼠白细胞减少的预防和治疗作用。方法　采用60 Co -γ射线造成外周血白细胞减少的动物模型进行试验 ,观察MPG防治由放疗所致白细胞减少的作用。结果　预先用MPG不同剂量对小鼠经口灌胃 (ig)或腹腔注射 (ip)用药 5天 ,给动物一次60 Co -γ射线全身照射 480Rad/ 3min ,及先给动物进行一次60 Co -γ射线全身照射 480Rad/ 3min后 ,用MPG不同剂量对小鼠ig或ip进行治疗。然后均于放疗后第 3天、第 5天计数白细胞总数 ,与单用放疗组相比具有显著性差异。结论　MPG具有明显的预防和治疗由60 Co -γ射线所致的小鼠白细胞减少的作用。     

苦参素对小鼠的急性毒性和外周血红细胞微核和精子畸变试验

背景与目的： 研究苦参素的急性毒性及遗传毒性。材料与方法： 采用LD50试验,外周血微核试验与精子畸变试验,按体重随机分为五组,以腹腔注射（i.p）方式给药。结果： 小鼠苦参素的LD50为(505±31)mg/kg。外周血24 h PCE、48 h PCE微核率显示：1/2 LD50、1/4 LD50、1/8 LD50组与阴性对照组相比均有统计学意义,且有一定的剂量反应关系。精子畸变试验中1/2 LD50组的畸变率与阴性对照组相比有统计学意义,1/4 LD50、1/8 LD50组与阴性对照组相比无统计学意义。结论： 苦参素基本属低毒类药物,在一定程度上有遗传毒性作用。