DNA damage in mouse organs and in human sperm cells by bisphenol A

Abstract

The in vivo genotoxic potential of bisphenol A using the comet assay in mice and in human sperm cells in vitro without metabolizing enzymes was studied. Male mice were exposed by oral gavage to the following doses of bisphenol A (0 125, 250 and 500?mg/kg body weight). DNA damage was investigated in liver, kidney, testes, urinary bladder, colon and lungs cells. In testicular cells, a significant increase in DNA strand breaks was observed in the lowest, but not in the medium or highest dose groups. Histopathological investigation of the testicular samples did not show any treatment dose-related effects. No DNA strand breaks were observed in any of the other investigated tissues. In human sperm cells in vitro, bisphenol A did not induce DNA strand breaks.     

The role of thymoquinone as antioxidant protection on oxidative stress induced by imidacloprid in male and female Swiss albino mice

The aim of the present study was to evaluate the possible protective effects of thymoquinone (TQ), an antioxidant agent, against imidacloprid (IMI)-induced oxidative stress in male and female mice. In total, 48 Swiss Albino male and female mice were fed a standard rodent diet and divided into 3 equal groups: the animals in the control group (vehicle treated) were given corn oil, the second group were orally administered 15 mg/kg/day IMI alone, and the third group were orally administered 15 mg/kg/day IMI and with TQ at 10 mg/kg/day for 21 days. During the experimental period, there were no significant changes between initial body weights and final body weights of IMI treated male and female mice. IMI produced significant increase in blood, liver, kidney, and heart malondialdehyde (MDA) levels and decrease in blood and liver glutathione (GSH) levels. In addition, IMI treatment decreased erythrocyte, liver, and kidney superoxide dismutase (SOD) activity in male mice and decreased erythrocyte and liver SOD activity in female mice. Erythrocyte catalase (CAT) activities were found to be low in male and female mice. However, treatment with TQ reversed IMI-induced oxidative stress, lipid peroxidation, and activities of antioxidant enzymes. Moreover, TQ exhibited protective action against the IMI-induced histopathological changes in tissues of male and female mice. In conclusion, TQ was found to be effective in protecting mice against IMI-induced oxidative stress by enhancing antioxidant defense mechanisms.     

镧、铈、钕对小鼠肝细胞线粒体的氧化损伤作用

轻稀土元素进入生物体后主要累积于肝脏,进入肝细胞,除蓄积在细胞核中,还存在于线粒体中。为探讨轻稀土元素对小鼠肝细胞线粒体的氧化损伤作用,选用5周龄雄性ICR小鼠分别以10、20和40mg·kg~(-1)的镧(La)、铈(Ce)和钕(Nd)灌胃,6周后测定小鼠肝细胞线粒体中超氧化物岐化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)的活性,以及谷胱甘肽(GSH)和丙二醛(MDA)的含量。结果显示,与对照组相比,La中剂量组和Ce低剂量组SOD活性显著升高,La高剂量组和Nd中、高剂量组中SOD活性显著降低(P<0.05,P<0.01);除个别剂量组外,各染毒组CAT和GPx活性与GSH含量显著降低(P<0.05,P<0.01);Nd各剂量组、La高剂量组和Ce高剂量组的MDA含量显著升高(P<0.05,P<0.01)。研究表明,La、Ce和Nd所导致的CAT和GPx活性以及GSH含量降低可能是造成肝细胞线粒体氧化损伤的主要原因。     

盐酸小檗碱对小鼠脾细胞的DNA损伤和氧化性损伤研究

为了探讨盐酸小檗碱对小鼠的DNA损伤和氧化性损伤。随机选取30只小鼠分成对照组以及7.5,15,30,60与120 mg?kg^-1实验组,处理后,应用小鼠脾细胞进行彗星实验与抗氧化酶实验。测定DNA损伤情况以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、过氧化物酶（POD）活性以及丙二醛（MDA）含量变化。对盐酸小檗碱的DNA损伤与氧化性损伤作用进行比较研究。研究结果表明：彗星实验中,随着盐酸小檗碱浓度的增加,尾部DNA含量、尾长与尾矩均增加,与阴性对照组相比差异有统计学意义（p<0.05或p<0.01）,且呈剂量-效应关系;超氧化物歧化酶(SOD)与过氧化氢酶(CAT)活性随盐酸小檗碱剂量增加逐渐降低,丙二醛(MDA)含量明显下降,过氧化物酶(POD)活性在7.5 mg?kg^-1时上升,而后逐渐下降。在60 mg?kg^-1和120 mg?kg^-1时,有极显著性差异（p<0.01）产生。由此可见,盐酸小檗碱对小鼠脾细胞有一定的损伤作用,能够引起小鼠脾细胞的DNA损伤和氧化性损伤。     

Dichloroacetate- and trichloroacetate-induced modulation of superoxide dismutase,catalase, and glutathione peroxidase activities and glutathione level in the livers of mice after subacute and subchronic exposures

Dichloroacetate (DCA) and trichloroacetate (TCA) were previously found to induce various levels of oxidative stress in the hepatic tissues of mice after subacute and subchronic exposures. The cells are known to have several protective mechanisms against production of oxidative stress by different xenobiotics. To assess the roles of the antioxidant enzymes and glutathione (GSH) in DCA- and TCA-induced oxidative stress, groups of B6C3F1 mice were administered either DCA or TCA at doses of 7.7, 77, 154, and 410 mg kg^?1 day^?1, by gavage for 4 weeks (4-W) and 13 weeks (13-W), and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as GSH were determined in the hepatic tissues. DCA at doses ranging between 7.7–410, and 7.7–77 mg kg^?1 day^?1, given for 4-W and 13-W, respectively, resulted in either suppression or no change in SOD, CAT, and GSH-Px activities, but doses of 154–410 mg DCA kg^?1 day^?1 administered for 13-W were found to result in a significant induction of the three enzyme activities. TCA administration on the other hand, resulted in increases in the SOD and CAT activities, but caused suppression of GSH-Px activity in both the periods. Except for the DCA doses of 77–154 mg kg^?1 day^?1 administered for 13-W that resulted in a significant reduction in the GSH levels, all other DCA as well as TCA treatments produced no changes in GSH. Since these enzymes are involved in the detoxification of the reactive oxygen species (ROS), superoxide anion (SA), and H₂O₂, it is concluded that SA is the main contributor to DCA-induced oxidative stress, while both ROS contribute to that of TCA. The increase in the enzyme activities associated with 154–410 mg DCA kg^1? day^?1 in the 13-W period suggest their role as protective mechanisms contributing to the survival of cells modified in response to those treatments.     

Responses of oxidative stress,genotoxicity and immunotoxicity as biomarkers in Theba pisana snails dietary exposed to silver nanoparticles

Silver nanoparticles (AgNPs) are now being of a great interest by ecotoxicological researchers. Their potential hazards to humans and other non-target organisms had led to crucial concerns. In this research, white radish leaf extract was used for the green synthesis of AgNPs. UV–Vis spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction (XRD) have been utilised to characterise the biosynthesised AgNPs. Furthermore, the present study aimed to investigate the ecotoxicological effects of 1?mM biosynthesised AgNPs on the land snail, Theba pisana after two weeks of exposure and one week recovery with respect to oxidative stress parameters; lipid peroxidation (LPO), reduced glutathione (GSH), catalase (CAT) and glutathione-S-transferase (GST), cytogenetic parameters; DNA content and micronucleus test, as well as immunological parameters; cell death, phagocytosis, lysosomal membrane stability (LMS), lectins, superoxide anion (O₂^?) generation, phenoloxidase (PO), peroxidase (POD) and haemocyanin (Hc) were examined. AgNPs have been biosynthesised successfully; the UV–vis spectrum exhibited a single and broad absorption band located between 375 and 415?nm, TEM image shows AgNPs formed were nearly spherical in shape with a mean size of 2.18–19.87?nm and the crystalline nature of nanoparticles was confirmed by XRD. After two weeks exposure, the result showed that AgNPs significantly increased LPO level as well as CAT and GST activities, cell death, cell abnormalities and Hc level, whereas, significant decline was found in DNA and GSH contents, phagocytic activity, LMS, lectins, O₂^? generation, POD and PO activities compared to the controls. After a week of recovery, most of the tested biomarkers in AgNP-exposed snails did not completely return to the control levels. The multiple measured parameters could be effectively used as sensitive biomarkers in the risk assessment of contaminants in the terrestrial ecosystem.     

镧、铈、钕对小鼠肝细胞核的氧化损伤作用

轻稀土元素进入生物体后主要累积于肝脏,进入肝细胞,分布于细胞核上.为探讨轻稀土元素对小鼠肝细胞核的氧化损伤作用,选用5周龄雄性封闭群(ICR)小鼠灌喂10、20和40 mg·kg-1的稀土元素镧(La)、铈(Ce)和钕(Nd),6周后测定小鼠肝细胞核中超氧化物岐化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(...     

利用不同植物进行DNA损伤彗星实验的方法比较

为了研究彗星实验在植物DNA损伤检测中的应用,以多种植物材料为对象,进行了植物彗星实验的比较研究.分别分离了蚕豆、菠菜、洋葱、菜豆、大蒜、水稻等植物组织的细胞核,并以彗星实验方法研究了H2O2引起的植物细胞核DNA损伤.电泳后发现H2O2处理组植物细胞核出现明显拖尾,而对照组没有出现拖尾或拖尾较小.研究结果表明彗星实验是一种可以在单细胞水平上研究植物DNA损伤程度的手段,具有灵敏、简单、快速的优点.采用合适的细胞核分离方法,能够将彗星实验应用于多种植物,研究其DNA损伤.蚕豆、菠菜、洋葱、菜豆、大蒜等植物的根尖和叶片都可以应用于植物彗星实验,但在本实验条件下利用水稻组织进行彗星试实验并没有获得明显的彗星图像,能否进行彗星实验可能受植物本身性质或实验条件等多种因素的影响.     

十溴二苯乙烷对草鱼幼鱼肝脏和肌肉组织氧化应激效应的影响

十溴二苯乙烷(DBDPE)是目前在全球范围内广泛使用的新型溴代阻燃剂,其环境风险已引起广泛关注,但目前仍缺乏针对水生生物的毒性研究数据。作者通过饲料中添加十溴二苯乙烷暴露的方式对草鱼幼鱼进行长期暴露实验,研究500、1 000和3 000 mg·kg~(-1)三个饲料添加剂量暴露组和1个对照组长期暴露对草鱼幼鱼肝脏和肌肉组织中氧化应激酶(SOD、CAT和GSH-PX)活性和抗氧化物质(GSH)含量的影响。结果显示:暴露8周后,随着DBDPE暴露水平的升高,草鱼幼鱼肝脏组织中氧化应激酶(SOD、CAT和GSH-PX)和抗氧化物质(GSH)均表现出低浓度诱导及高浓度抑制的效应。500和1 000 mg·kg~(-1)剂量组草鱼幼鱼肝脏组织中SOD、CAT和GSH-PX活性和GSH含量均显著高于对照组(P0.05),且均在500 mg·kg~(-1)剂量组达到最高。3 000 mg·kg~(-1)剂量组SOD、CAT和GSH-PX活性和GSH含量低于500和1 000 mg·kg~(-1)暴露组,但与对照组无显著性差异(P0.05)。草鱼幼鱼肌肉组织中氧化应激酶活性变化甚微,3个浓度剂量组肌肉组织中SOD、CAT活性和GSH含量以及500 mg·kg~(-1)剂量组GSH-PX活性与对照组均无显著性差异(P0.05)。研究成果表明DBDPE暴露影响草鱼幼鱼肝脏组织的抗氧化防御系统,可以诱导草鱼幼鱼产生氧化应激效应。     

丙烯腈诱导的氧化应激对大鼠肝脏内质网应激信号通路的影响

为探讨丙烯腈(acrylonitrile,ACN)诱导的大鼠肝脏氧化损伤对内质网应激(endoplasmic reticulum stress,ERS)信号通路的影响,我们将50只SPF级成年雄性SD大鼠按体重随机分为5组,每组10只。各组分别以12.5、25.0、50.0 mg·kg~(-1)ACN灌胃染毒,N-乙酰半胱氨酸(N-acetylcysteine,NAC)干预组先用300.0 mg·kg~(-1)NAC灌胃30 min后再灌50.0 mg·kg~(-1)ACN,对照组以0.5 mL·(100 g)~(-1)的玉米油灌胃,1次·天~(-1),6天·周~(-1),共计13周。染毒结束后,检测肝脏组织氧化还原酶活力及丙二醛(malondialdehyde,MDA)含量,GRP78、CHOP及caspase-12 mRNA及蛋白表达水平。结果显示:低、中ACN组大鼠肝脏GSH含量显著低于对照组(P0.05);低ACN组大鼠肝脏GSH-Px活力、SOD活力及MDA含量均显著高于对照组(P0.05);中、高ACN组大鼠肝脏CAT活力明显低于对照组(P0.05)。NAC干预后可逆转ACN诱导的大鼠肝脏GSH含量、MDA含量及SOD活力的变化。RT-PCR结果显示,高ACN组大鼠肝脏GRP78、CHOP、caspase-12 mRNA表达水平与对照组比较均升高(P0.05)。NAC干预后,CHOP、caspase-12 mRNA表达水平与高ACN组比较均降低(P0.05)。Western Blot结果显示,高ACN组大鼠肝脏GRP78、CHOP、caspase-12蛋白表达水平与对照组比较均升高(P0.05),NAC干预后可逆转以上作用。结果表明,ACN慢性染毒对大鼠肝脏的氧化损伤可激活ERS信号通路,NAC可减轻氧化损伤的程度而阻断ERS信号通路,这可能是ACN产生肝脏毒性的机制之一。     

汽油尾气对人肺腺癌A549细胞的氧化损伤效应研究

为研究汽油燃烧汽车尾气(简称汽油尾气)的氧化损伤效应及其可能的毒作用机制,以人肺腺癌A549细胞为研究对象,采用MTT试验测试汽油尾气对细胞的毒性作用;通过测定细胞内超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性了解细胞在汽油尾气作用下抗氧化水平的改变;并用彗星试验检测汽油尾气对细胞DNA氧化损伤及修复的影响．结果显示汽油尾气在浓度≥0．0625L·mL-1时即显示出明显的细胞毒性;汽油尾气作用下A549 细胞SOD及GSH-Px活性均下降,在一定的浓度范围内与对照组比较有统计学差异(p<0．05)．汽油尾气可诱导 A549细胞不同程度的DNA氧化损伤,且细胞拖尾率和DNA迁移长度均随着汽油尾气浓度的增加而增加;损伤后 A549细胞修复发生较快,3小时内基本修复完全．提示汽油尾气具有明显的细胞毒性作用,可影响A549细胞抗氧化酶活性,并可导致DNA的氧化损伤．     

Influence of marine alga against mercury-induced biochemical changes,structural destabilization,and genotoxicity in marine tiger fish,Therapon jarbua

This study elucidated the protective role of alga against mercury (Hg)-induced toxicity in marine fish. Bath immersion with mercury chloride (HgCl) [0.125 and 0.25?ppm] in combination with the algal extract (3?ppm) to Therapon jarbua offered a significant protection against Hg only induced disturbed liver function, damaged histoarchitecture, elevated oxidative stress, and DNA fragmentation of tissues. Mercury exposure decreased hepatic superoxide dismutase (SOD), catalase (CAT) activities, and the level of nonprotein-soluble thiol (NPSH, GSH), with a concomitant increase in thiobarbituric acid reactive substances (TBARS) in the gill, kidneys, liver, and blood. Algal supplementation diminished the rise in TBARS restoring CAT, SOD, and GSH levels to control. Reduced generation of free radicals may be correlated to protect DNA stability and morphology. This study indicates the ability of alga to ameliorate Hg-mediated injuries. In conclusion, Kappaphycus alvarezii extract did not show any toxicity and its safety is suggestive for using as a supplement in fish food.     

Mercuric chloride induced proteotoxicity and structural destabilization in marine fish (Therapon jarbua)

The reaction byproducts derived from lipid peroxidation (LPO), as well as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) enzyme activities were measured in tissues of marine fish (Therapon jarbua) exposed to mercuric chloride (HgCl) in water dispersions of 0.125 or 0.25 ppm. LPO was significantly increased in various tissues relative to control values after 96-h exposure. SOD and GPx activities significantly decreased after exposure to first two doses but significantly elevated CAT in Dose II kidney and liver tissues. The elevated levels of LPO, decreased activities of SOD and GPx, and increased CAT activities in all tissues examined in T. jarbua are an index of oxidative stress in fish. Structural analysis by scanning electron microscopy studies revealed the structural deformation in HgCl₂-exposed animals. These observations suggest that HgCl acts as a mediator in free radical generation. The increase in CAT and decrease in SOD and GPx activities in these tissues may be an adaptive response.     

碲化镉量子点对小鼠睾丸组织的氧化损伤（Effects of CdTe Quantum Dots on the Antioxidant Enzymes Activity and Lipid Peroxidation in Testes of Mice）

为探讨碲化镉量子点(CdTeQDs)对小鼠睾丸的急性氧化损伤作用,将20只雄性ICR小鼠随机分成4组:对照组、1d、3d、7d(3个不同时间组),采用尾静脉注射进行一次性染毒2.5μmol·kg-1CdTeQDs,对照组注射等体积生理盐水.染毒后对睾丸的脏器系数以及组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)含量分别进行测定,从而检测CdTeQDs对睾丸组织的急性氧化损伤作用.结果显示,与对照组相比,随染毒时间的延长,睾丸脏器系数无显著性变化(p>0.05);GSH-Px和SOD活性随染毒时间的延长呈逐渐升高趋势;而CAT活性呈逐渐降低趋势,且与对照组差异显著(p<0.01);MDA含量显著高于对照(p<0.01),且随时间变化不大.CdTeQDs染毒可导致小鼠睾丸组织氧化损伤,其损伤程度与染毒时间之间具有一定的时间-效应关系.     

纳米硫化镉对A549细胞的损伤研究

研究纳米硫化镉(Nano-Cd S)材料对肺癌细胞系A549的毒性及氧化损伤作用。培养A549细胞,经传代后接种于6孔板中,每孔2 m L完全培养基,接种次日进行染毒。用直径20~30 nm、长度80~100 nm的Nano-Cd S进行染毒,染毒浓度分别为0、5、10、20、40和80 mg·L~(-1)。染毒24 h后用MTT检测细胞存活率,以存活率在80%左右的浓度为后续实验染毒浓度。应用流式细胞技术,用荧光探针法检测A549细胞的活性氧(reactive oxygen species,ROS)含量,PI-Annexin-V法检测细胞凋亡情况;用试剂盒检测细胞中超氧化物岐化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)活性以及丙二醛(malondialdehyde,MDA)含量,判断细胞氧化损伤情况。不同浓度Nano-Cd S处理细胞24 h之后,细胞存活率随剂量的增加而下降,浓度为10、20、40和80μg·L~(-1)时,存活率分别为(88.71%±0.80%)、(81.93%±3.06%)、(75.23%±1.13%)和(70.66%±5.63%),且各组间差异均具有统计学意义(P0.05)。以浓度为10和20 mg·L~(-1)的Nano-Cd S染毒24 h后,胞内ROS含量和细胞凋亡率随染毒剂量的增加而增加(P0.05);浓度为10 mg·L~(-1)时,细胞凋亡率为(6.26%±0.44%)。与对照相比,各染毒组SOD和CAT活性和MDA含量升高,20 mg·L~(-1)染毒组SOD和CAT活性和MDA含量高于10 mg·L~(-1)染毒组(P0.05)。研究表明,纳米硫化镉能引起A549细胞的氧化损伤和细胞凋亡,具有明显的细胞毒性。     

Oxidative stress mediated cytotoxicity of TiO2 nano anatase in liver and kidney of Wistar rat

This study examined the adverse effects of TiO₂ nanoparticle (nano-TiO₂) on the kidney and liver of Wistar rats. Changes of serum biochemical parameters and pathological lesions indicated that liver and kidney were significantly affected in animals treated with 50?mg?kg^?1 of nano-TiO₂. The inverse relationship between the level of reactive oxygen species and the activities of superoxide dismutase, catalase, and glutathione peroxidase indicates that nano-TiO₂ induces oxidative stress. A significant increase in the apoptosis of liver and kidney in a dose-dependent manner was also observed. The ultrastructural observations confirmed the internalization of nano-TiO₂ and their direct involvement in the mitochondria-mediated cytotoxicity. Data indicated that nano-TiO₂ induce oxidative stress which produces genotoxicity such as oxidative DNA damage, micronuclei (MN) induction, and cell apoptosis in liver and kidney.     

纳米硫硒化镉对小鼠肾脏和脑组织SOD活力和MDA含量的影响

为了探讨纳米硫硒化镉(CdSeS)对小鼠肾脏和脑组织的急性氧化损伤作用,将20只雄性昆明小鼠随机分成4组,采用尾部静脉注射进行一次性染毒,3个染毒组分别注入0.1、0.2、0.4mg·mL-1的纳米CdSeS粉末(20～30nm)悬液1mL,对照组注入等体积生理盐水.染毒3d后对肾脏和脑组织匀浆中超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量分别进行测定,从而检测纳米CdSeS对肾脏和脑组织的急性氧化损伤作用.结果显示,随着纳米CdSeS染毒浓度的升高,小鼠肾脏和脑组织中SOD活力呈逐渐降低趋势,而MDA含量呈逐渐升高趋势,均显示出一定的剂量-效应关系;较高浓度组(肾:ρCdSeS≥0.2mg·mL-1;脑:ρCdSeS≥0.4mg·mL-1)SOD活力、MDA含量与对照具有显著性差异(p<0.05,p<0.01),而较低浓度组则没有显著性差异(p>0.05).以上结果提示纳米CdSeS能够对小鼠肾脏和脑组织造成氧化损伤,并且能穿过血脑屏障作用于脑部。     

Protective effect of Spirulina platensis against aluminium-induced nephrotoxicity and DNA damage in rats

The protective effect of Spirulina platensis (SP) powder against aluminium-induced nephrotoxicity and DNA damage in rats was studied. Male rats receiving daily 40 mg/kg b.wt. aluminium chloride (AlCl₃) orally had increased serum levels of urea and creatinine, up regulated kidney injury molecule-1 and tissue inhibitor of metalloproteinase-1 genes, down regulated catalase and glutathione peroxidase genes, and increased all parameters of kidney DNA damage using comet assay. Treatment with SP alleviated all AlCl₃-induced effects of toxicity, especially when the animals were pre-treated.     

硝基甲苯对小鼠睾丸生殖细胞DNA的损伤作用

为提供硝基甲苯的环境遗传毒理学依据和建立鱼类生殖细胞的培养方法,采用昆明小鼠睾丸支持细胞/生殖细胞共培养法以及彗星实验,研究了2,4-二硝基甲苯(2,4-DNT)、2,6-二硝基甲苯(2,6-DNT)、对硝基甲苯(4-NT)对小鼠睾丸生殖细胞DNA的损伤作用.结果表明,3种受试硝基甲苯化合物均能够诱导小鼠睾丸生殖细胞DNA单链断裂,而且其受损率与剂量对数具有明显的剂量-效应关系.2,4-DNT、2,6-DNT以及4-NT的各个剂量浓度引起细胞DNA损伤的程度,与对照组相比,均具有显着性差异(p<0.01,p<0.05).受试化合物的毒性顺序为2,6-DNT>2,4-DNT>4-NT,DNA的损伤作用二硝基甲苯大于单硝基甲苯.提示在体外条件下,2,4-DNT、2,6-DNT和4-NT具有生殖毒性,可以引起小鼠睾丸生殖细胞DNA损伤.