Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells

The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor –kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.     

Pu-erh black tea supplementation decreases quinocetone-induced ROS generation and oxidative DNA damage in Balb/c mice

Quinocetone (3-methyl-2-quinoxalinbenzenevinylketo-1,4-dioxide, QCT), a new feed antibacterial agent of quinoxaline-1,4-dioxides family, has been used as an animal growth promoter. However, few data about its potential toxicity in vivo were available. In this study, genotoxicity of QCT and the relationship with oxidative stress were investigated. Balb/c mice with both sexes were administrated with QCT (12000, 6000 and 3000 mg/kg/bw, respectively) by gavage acutely. DNA damage, generation of reactive oxygen species (ROS) and activity of antioxidative system (total antioxidative capacity, glutathione, glutathione peroxidase, superoxide dismutase and catalase) in liver and kidney were determined. Moreover, Pu-erh black tea extract (BTE) was co-administrated with QCT to evaluate its protective effect against QCT-induced genotoxicity. The DNA damage was observed in all the groups treated with single QCT except the liver with dose of 3000 mg/kg/bw. ROS was accumulated and antioxidative system was suppressed both in liver and kidney. However, the DNA damage, as well as the ROS, was decreased, while the activity of antioxidative system was increased in mice after co-administration of QCT and BTE. These data demonstrate that oxidative stress mediated the genotoxicity induced by QCT in vivo. Furthermore, this oxidative DNA damage can be attenuated by pre-supplementation of BTE.     

Nrf2/ARE is the potential pathway to protect Sprague–Dawley rats against oxidative stress induced by quinocetone

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) is a newly used veterinary drug which has been proven to promote feed efficiency and growth of animals; however, its potential toxicity can’t be ignored. Therefore, the present study was aimed to investigate the nephrotoxicity of QCT and the oxidative stress induced by it. Sprague–Dawley rats (SD rats) were randomly divided into four groups with doses of 2400, 800, 50 and 0 mg/kg/day with administration of QCT for 4 weeks. Results proved that QCT could induce nephrotoxicity and this phenomenon had dose dependent manner. Simultaneously, this phenomenon was accompanied by intracellular reactive oxygen species (ROS) accumulation, enhanced lipid peroxidation and inhibited antioxidant system, i.e. glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSH). Additionally, the higher expression of Nrf2 in QCT treated groups illustrated that QCT-induced oxidative stress would be partly mitigated by the induction of phase II detoxifying enzymes via increasing Nrf2 expression.     

Pu-erh black tea extract supplementation attenuates the oxidative DNA damage and oxidative stress in Sprague-Dawley rats with renal dysfunction induced by subchronic 3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide exposure

3-Methyl-2-quinoxalin benzenevinylketo-1,4-dioxide (Quinocetone, QCT), has been used to treat dysentery and promote growth in animal feeding. However, available data show that QCT has potential nephrotoxicity. The present study was designed to investigate the protective effects of Pu-erh black tea extract (PBTE) which is a traditional remedy in China with antioxidant properties against oxidative DNA damage and oxidative stress in a rat model of QCT-induced renal dysfunction. Increased serum creatinine, blood urea nitrogen, pathological lesions, urinary 8-hydroxy 2-deoxyguanosine (8-OHdG) and renal DNA damage were observed in the QCT-fed rats. These were accompanied by intracellular reactive oxygen species accumulation, enhanced lipid peroxidation, and inhibited antioxidant system, i.e., glutathione glutathione S-transferase, glutathione peroxidase and glutathione reductase. Oral administration of PBTE effectively suppressed QCT-induced renal dysfunction, as evidenced by reduced serum creatinine, urinary 8-OHdG and DNA damage in isolated renal cells, amelioration of oxidative stress and modulation of antioxidative system. In conclusion, PBTE administration ameliorated QCT-induced nephrotoxicity by maintaining DNA's double-helix architecture and mitigating oxidative stress.     

低温联合还原型谷胱甘肽对肝细胞缺血-再灌注损伤中bcl-2及bax的影响作用

目的观察低温联合还原型谷胱甘肽对缺血-再灌注诱导的L02肝细胞凋亡的影响,并探索相关分子机制。方法M1T11比色法检测低温联合还原型谷胱甘肽对细胞活力的影响;试剂盒检测低温联合还原型谷胱甘肽对细胞丙二醛（MDA）水平、乳酸脱氢酶（LDH）释放及超氧化物歧化酶（SOD）活力的影响;激光共聚焦显微镜检测细胞内活性氧簇（ROS）生成;Westernblot法检测低温联合还原型谷胱甘肽对bcl-2及bax蛋白表达水平的影响。结果低温联合还原型谷胱甘肽能明显抑制缺血-再灌注诱导的L02肝细胞活力降低（P〈0．05）;低温联合还原型谷胱甘肽处理细胞能明显抑制缺血-再灌注诱导的L｜02肝细胞MDA生成增加、LDH水平增高及SOD活力降低（P〈0．05）;低温联合还原型谷胱甘肽处理细胞能明显抑制缺血-再灌注诱导的L02肝细胞内bcl-2蛋白表达水平降低及bax蛋白表达水平增高（P〈0．05）。结论低温联合还原型谷胱甘肽可能通过上调bcl-2的表达及下调bax的表达抑制缺血-再灌注诱导的L02肝细胞凋亡发生。     

Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear cells: protective effects of curcumin and α-tocopherol

The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0–21?μg/ml) for 6, 12, and 24?h, and in combination with curcumin (9.2?μg/ml) or α-tocopherol (4.3?μg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p?相似文献   

The relationship between the anti-inflammatory effects of curcumin and cellular glutathione content in myelomonocytic cells

Oxidative stress plays an important role during inflammatory diseases and recent therapies have focused on antioxidant administration to diminish oxidative stress and to arrest inflammatory processes. In this study, we investigated the impact of the GSH modulating effects of curcumin, a naturally derived polyphenol, on inflammatory processes in myelomonocytic U937 cells. One hour after administration of 10 micromol/l curcumin reactive oxygen species (ROS) production was significantly increased in undifferentiated U937 cells (+43%). Twenty-four hour after addition of curcumin, a significantly decreased ROS concentration was found (-32%), whereas GSH (+110%) and GSSG (+88%) content increased. A higher concentration of curcumin (25 micromol/l) caused an even stronger increase of GSH (+145%) and GSSG (+101%), but significantly decreased percentage of living cells to 84%. The increased GSH content of differentiated U937 cells after pre-incubation with curcumin was associated with lowered ROS production, nuclear factor kappa B (NFkappaB) activation (-34%) and tumor necrosis factor alpha (TNF-alpha) secretion (-51%) after LPS exposure. Curcumin inhibited TNF-alpha formation was also seen after GSH depletion by buthionine sulfoximine (BSO). This study shows that the antioxidative effects of curcumin are preceded by an oxidative stimulus, which is time and dose-dependent. Excessive concentrations of curcumin may even harm cells, as cell viability was decreased, in spite of elevated GSH contents. There was no clear relationship between intracellular GSH concentrations and the anti-inflammatory effects of curcumin.     

Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons

AIM: To investigate the effect of curcumin on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat cortical neurons and to explore the possible mechanism. METHODS: Primary cultured rat cortical neurons wereperformed in vitro and cell viability was measured by MTT assay. DNA fragmentation was used to evaluate cellapoptosis. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (Aψm) was determined by flow cytometric assay. Cellular glutathione (GSH) content was measured by spectrophotometer.‘ Bcl-2family proteins, cytochrome c, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) were detected byWestern blot. RESULTS: Exposure of tBHP 100 μmol/L to neurons for 60 rain resulted in △ψm loss and cyto-chrome c release from mitochondria and subsequent activation of caspase-3 and PARP cleavation, and cell apoptosis.After removal of tBHP and then further treatment with curcumin (2.5-20 μmol/L) for 18 h, curcumin abrogated △ψm loss and cytochrome c release, blocked activation of caspase 3, and altered the expression of Bcl-2 family.Further curcumin treatment also prevented cellular GSH and decreased intracellular ROS generation markedly.Curcumin eventually attenuated tBHP-induced apoptosis in cortical neurons. CONCLUSION: Curcumin mayattenuate oxidative damages in cortical neurons by reducing intracellular production of ROS and protecting mito-chondria from oxidative damage.     

Oxidative damage and OGG1 expression induced by a combined effect of titanium dioxide nanoparticles and lead acetate in human hepatocytes

Titanium dioxide (TiO(2)) is a widely used nanomaterial that can cause biological damage through oxidative stress. At low concentrations, TiO(2) can interact with lead acetate (PbAc) to produce different toxic responses, compared with TiO(2) or PbAc alone. In this study, we utilized the following as indicators of toxic responses in human embryo hepatocytes (L02): reactive oxygen species (ROS), reduced glutathione (GSH), superoxide dismutase (SOD), and the DNA adducts 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxoguanine DNA glycosylase homolog 1 (OGG1). These were used to evaluate the oxidative stress of TiO(2) (at 0.001, 0.01, 0.1, 1, and 10 μg mL(-1)) mixed with PbAc (1 μg mL(-1)) on L02 cells without photoactivation. Compared with the negative control (1‰ dimethyl sulfoxide), TiO(2) mixed with PbAc induced increased release of ROS (at 0.001, 0.01, 0.1, 1, 10 μg mL(-1) TiO(2)), intracellular SOD activity (at 0.1 and 0.01 μg mL(-1) TiO(2)), GSH levels (at 0.01-1 μg mL(-1) TiO(2)), 8-OHdG levels (at 1 and 10 μg mL(-1) TiO(2)), OGG1 expression (at 0.001-1 μg mL(-1) TiO(2)), and cytotoxicity (at 0.1, 1, and 10 μg mL(-1) TiO(2)) in L02 cells. There were no significant changes in ROS, GSH, SOD, 8-OHdG, or OGG1 levels when L02 cells were treated with TiO(2) alone or PbAc alone. These findings indicate that TiO(2) and PbAc in combination induce cytotoxicity and oxidative stress in L02 cells in the absence of photoactivation.     

人参皂苷保护小鼠精原细胞氧化损伤的研究

目的观察人参皂苷对活性氧引起的小鼠睾丸生殖细胞氧化损伤的保护作用。方法利用体外培养的小鼠精原细胞建立氧化应激模型,通过检测生殖细胞活性、脂质过氧化产物丙二醛(MDA)生成、超氧化物歧化酶(SOD)活性和谷胱甘肽(GSH)水平评价人参皂苷对精原细胞氧化损伤的缓解作用。结果次黄嘌呤/黄嘌呤氧化酶(HX/XO)体系产生的活性氧可引起生殖细胞活性降低、MDA的生成量增加、SOD活性和GSH水平降低,而添加人参皂苷(10mg·L-1)能恢复HX/XO引起的生殖细胞活性、SOD活性和GSH水平的下降以及MDA生成的增加。结论人参皂苷可通过抗氧化作用保护活性氧引起的小鼠精原细胞氧化损伤。     

Protective effect of curcumin against formaldehyde‐induced genotoxicity in A549 Cell Lines

Formaldehyde is ubiquitous in the environment. It is known to be a genotoxic substance. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde‐induced genotoxicity in human lung cancer cell lines A549. To test this hypothesis, we investigated the effects of antioxidant on formaldehyde‐induced genotoxicity in A549 Cell Lines. Formaldehyde exposure caused induction of DNA–protein cross‐links (DPCs). Curcumin is an important antioxidant. Formaldehyde significantly increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activity. In addition, the activation of NF‐κB and AP‐1 were induced by formaldehyde treatment. Pretreatment with curcumin counteracted formaldehyde‐induced oxidative stress, ameliorated DPCs and attenuated activation of NF‐κB and AP‐1 in A549 Cell Lines. These results, taken together, suggest that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Lethal and sublethal effects of the emerging contaminant oxytetracycline on the embryo-larval development of Rhinella arenarum

The antibiotic oxytetracycline (OTC) is commonly used in animal production and can enter aquatic ecosystems, causing adverse effects on non-target species. The aim of this work was to evaluate the lethal and sublethal effects of OTC on the embryonic and larval period of Rhinella arenarum, through standardized bioassays and oxidative stress (catalase-CAT-, superoxide dismutase-SOD-, glutathione S-transferase-GST-, reduced glutathione-GSH- and lipid peroxidation-TBARS-), neurotoxicity (acetylcholinesterase-AChE- and butyrylcholinesterase-BChE-) and genotoxicity (micronuclei test) biomarkers. Mortality was time and stage dependent, being the embryos (504 h-LC50 = 64.04 mg/L) more sensitive than the larvae (504 h-LC50 = 97.74 mg/L). Alterations in the oxidative stress biomarkers were observed mainly in larvae: CAT, SOD and GST decreased and GSH increased significantly. In embryos, only GST decreased significantly. Also, OTC increased the AChE and BChE activities but did not increase the micronuclei frequency. This study shows evidence that the presence of OTC in the environment may have negative effects on amphibians.     

l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes

l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.     

Anti-oxidative and anti-genotoxic effects of carnosine on human lymphocyte culture

The aim of this study was to investigate the effects of carnosine, a biological antioxidant, on the oxidative stress and genotoxicity by a single dose of carbon tetrachloride (CCl(4); 5 mM) in the human lymphocyte culture. We studied the anti-genotoxic effects of carnosine by using sister chromatid exchange (SCE) test system. Also, the anti-oxidative effects of carnosine were evaluated by using superoxide dismutase (SOD), glutathione peroxidase (GPx), total glutathione (GSH) and malondialdehyde (MDA) assay. The SCE frequency was increased when treated with CCl(4). Carnosine at 10 and 20 mM reduced SCE frequency in the human lymphocyte (p < 0.001). In addition, CCl(4) treatment significantly depleted the level of GSH, reduced the activity of SOD and GPx and elevated the level of MDA (p < 0.001). Carnosine treatment led to significant attenuation of CCl(4)-induced oxidative stress by normalization of the activities of SOD and GPx and the level of GSH and MDA (p < 0.05 or 0.001). These results suggest that carnosine could provide anti-oxidative and anti-genotoxic protection for the oxidative and genotoxic agents that cause many diseases including cancer and neurodegenerative disease.     

莲心总碱对脂多糖和D-氨基半乳糖诱导小鼠急性肝衰竭肝脏的保护作用

目的：研究莲心总碱（TAENN）对脂多糖和D-氨基半乳糖（LPS/GalN）诱导小鼠急性肝衰竭肝脏的保护作用及可能作用机制。方法：昆明种雄性小鼠随机分为4组：正常对照组、模型组、TAENN高剂量组（100 mg·kg^-1）、TAENN低剂量组（30 mg·kg^-1）。腹腔注射LPS/GalN建立小鼠急性肝衰竭模型;通过生存曲线分析、HE组织化学染色、肝脏指数和血清转氨酶活性分析评价动物肝损伤程度;通过检测血清及肝脏内中SOD、GSH、MDA、ROS、CAT、GSH-Px水平评价小鼠整体和肝脏内氧化应激的状况。结果：口服TAENN能有效降低LPS/GalN诱导的小鼠死亡,HE染色观察显示TAENN能明显减轻LPS/GalN诱导的肝脏显微结构变化;此外,TAENN明显缓解了LPS/GalN诱导的肝脏肿大,降低了小鼠血清中ALT和AST活性水平（P<0.01）。进一步研究表明,TAENN明显降低了模型小鼠血清中MDA的含量,而血清GSH和SOD水平则明显增加（P<0.01）;经TAENN处理后,小鼠肝组织中ROS和MDA的相对含量降低,而肝脏GSH、SOD、CAT和GSH-Px水平则显著增加（P<0.01）。结论：TAENN能有效缓解LPS/GalN诱导的小鼠肝衰竭,且这种对肝脏的保护作用与其抑制LPS/GalN诱导的肝脏氧化应激相关。     

Salviolone protects against high glucose-induced proliferation,oxidative stress,inflammation, and fibrosis of human renal mesangial cells by upregulating membrane metalloendopeptidase expression

As one of complications of diabetes mellitus, diabetic nephropathy is related to renal dysfunction. Membrane metalloendopeptidase (MME) is associated with the pathogenesis of diabetic nephropathy and exerts a protective function in high glucose (HG)-treated podocytes. Salviolone, one of important bioactive components from Salvia miltiorrhiza, possesses an anti-inflammatory activity. However, the roles of salviolone in renal mesangial cell dysfunction under HG condition remain unknown. The targets of salviolone in diabetic nephropathy were predicted by bioinformatics analysis. Relative mRNA level of MME was detected by qPCR in HG-treated human renal mesangial cells (HRMCs). Cell viability was analyzed using CCK-8 assay. Cell proliferation was investigated by EdU staining. Oxidative stress was evaluated by detection of ROS generation and levels of oxidative stress-related biomarkers. The inflammatory cytokines and fibrosis-related biomarkers were examined by ELISA. Our results showed that MME expression was decreased in diabetic nephropathy and HG-treated HRMCs. Salviolone increased MME level in HG-treated HRMCs. Salviolone mitigated HG-induced HRMC proliferation by increasing MME expression. Salviolone attenuated HG-induced ROS generation, MDA level increase, and SOD activity decrease through upregulating MME expression. Moreover, salviolone suppressed HG-induced increase of levels of TNF-α, IL-1β, IL-6, fibronectin, and collagen IV through upregulating MME expression. In conclusion, s alviolone attenuates proliferation, oxidative stress, inflammation, and fibrosis in HG-treated HRMCs through upregulating MME expression.     

Responses of biomarkers in wild freshwater mussels chronically exposed to complex contaminant mixtures

Subcellular biochemical biomarkers are valuable early warning indicators of environmental contaminant effects. Thus, the present study evaluated several biomarkers and the relationships among them in wild freshwater mussels (Lasmigona costata) from a gradient of metal exposure and differential levels of other urban-related influences in the Grand River (ON, Canada). The biomarkers examined are related to metal exposure [gill ion and metal concentrations (Na, K, Ca, Mg, Cd, Cu, Ni, Pb and Zn)], oxidative status [reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), antioxidant capacity (ACAP)], sulfhydryl (SH) metabolism [glutathione (GSH), protein sulfhydryl groups (SH protein), glutathione S-transferase (GST), glutathione reductase (GR)], and lipid peroxidation. Gill metal concentration increased proportionally to waterborne metal concentration and disturbances in osmotic and divalent cations (Ca and Mg) concentrations were observed. This suggests that the observed effects are associated with metal exposure, although simultaneous relationships with other contaminants are also possible. Oxidative status biomarkers (ROS, SOD, CAT and ACAP) were more sensitive to urban-influences than gill metal concentration. In contrast, biomarkers involving SH metabolism (GSH, SH protein, total SH, GR and GST) were more correlated with gill metal concentration. Oxidative damage occurred when both metal and urban-related influences were high. Mechanistically, the way of dealing with oxidative stress changed when mussels were exposed to high levels of contaminants. The reduction in ROS content, SOD and CAT activity, and ACAP accompanying the stimulation of detoxification metabolism via SH (GSH and SH protein contents, GST and GR activities) and their association with gill metal concentration are discussed.     

Nickel oxide nanoparticles induce cytotoxicity,oxidative stress and apoptosis in cultured human cells that is abrogated by the dietary antioxidant curcumin

Nickel oxide nanoparticles (NiO NPs) are increasingly utilized in a number of applications. However, little is known about the toxicity of NiO NPs following exposure to human cells. This study was designed to investigate NiO NPs induced cytotoxicity, oxidative stress and apoptosis in cultured human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells. The results show that cell viability was reduced by NiO NPs and degree of reduction was dose-dependent. NiO NPs were also found to induce oxidative stress in dose-dependent manner indicated by depletion of glutathione and induction of reactive oxygen species and lipid peroxidation. Induction of caspase-3 enzyme activity and DNA fragmentation, biomarkers of apoptosis were also observed in NiO NPs exposed cells. Preventive potential of a dietary antioxidant curcumin against NiO NPs induced toxicity in HEp-2 MCF-7 cells was further examined. We found that co-exposure of curcumin significantly attenuated the cytotoxicity and oxidative stress induced by NiO NPs in both types of cells. This is the first report showing that NiO NPs induced ROS mediated cytotoxicity and apoptosis that is abrogated by curcumin. The pharmacological potential of curcumin against NiO NPs induced toxicity warrants further investigation.     

Oxidative damage and genotoxic effect in mice caused by sub-chronic exposure to low-dose volatile organic compounds

Abstract

Volatile organic compounds (VOCs) are widely used as constituents of household chemicals. Although adverse health effects have been reported, long-term exposure to low-level VOCs mixture has not been studied. Especially, there is a lack of substantial information on the sensitive biomarkers and carcinogenic markers. In the present study, we examined oxidative stress and genotoxic effects of sub-chronic low-dose VOCs mixture (formaldehyde, benzene, toluene and xylene). Male Kunming mice were exposed to 0 (control) and three different doses of VOCs mixture (group 1S, 5S and 10S) for 90?d (2?h/d). Group 1S is 0.10, 0.11, 0.20 and 0.20?mg/m³, group 5S is 0.50, 0.55, 1.00 and 1.00?mg/m³, group 10S is 1.00, 1.10, 2.00 and 2.00?mg/m³, which, respectively, corresponded to 1, 5 and 10 times of indoor air quality standard (IAQS) in China. One day following VOCs exposure, oxidative stress markers in lung, 8-hydroxy-2′-deoxyguanosine in bronchoalveolar lavage fluid and genotoxicity (DNA damage) in liver were examined. Results showed that exposure to VOCs (IAQS dose) resulted in oxidative damages of lung, which were supported by the significant changes on reactive oxygen species, reduced glutathione (GSH), GSH S-transferase, total antioxidative capacity, malondialdehyde, protein carbonyl and nitric oxide (NO). Moreover, oxidative stress markers in group 5S and 10S (except NO) in lung were affected significantly. In addition, VOCs exposure also induced significantly DNA damage in liver. Our study suggested long-term VOCs inhalation at low levels caused oxidative stress and genotoxicity response in mice. Since effects were seen at the current IAQS level, further studies below this level are necessary.     

Genotoxic and oxidative stress effects of 2-amino-9H-pyrido[2,3-b]indole in human hepatoma G2 (HepG2) and human lung alveolar epithelial (A549) cells

Abstract

2-Amino-9H-pyrido[2,3-b]indole (AαC), which is present in high quantities in cigarette smoke and also in fried food, has been reported to be a probable human carcinogen. However, few studies have reported on the genotoxicity and oxidative stress induced by AαC. This study investigated the genotoxic effects of AαC in human hepatoma G2 (HepG2) and human lung alveolar epithelial (A549) cells using the comet assay. Significant increases in DNA fragment migration indicated that AαC causes serious DNA damage in HepG2 and A549 cells. The role of oxidative stress in the mechanism of AαC-induced genotoxicity was clarified by measuring the level of intracellular reactive oxygen species (ROS), the GSH/GSSG ratio and the formation of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage. The results showed that the levels of ROS and 8-OHdG increased, whereas the GSH/GSSG ratio decreased. The concentration of 8-OHdG was positively related to DNA damage. Taken together, these results indicate that AαC can induce genotoxicity and oxidative stress and that AαC likely exerts genotoxicity in HepG2 and A549 cells through ROS-induced oxidative DNA damage. This is the first report to describe AαC-induced genotoxic and oxidative stress in HepG2 and A549 cells.