[Show abstract][Hide abstract] ABSTRACT: Citreoviridin (CIT) is a mycotoxin derived from fungal species in moldy cereals. In our previous study, we reported that CIT stimulated autophagosome formation in human liver HepG2 cells. Here, we aimed to explore the relationship of autophagy with lysosomal membrane permeabilization and apoptosis in CIT-treated cells. Our data showed that CIT increased the expression of LC3-II, an autophagosome biomarker, from the early stage of treatment (6 h). After treatment with CIT for 12 h, lysosomal membrane permeabilization occurred, followed by the release of cathepsin D in HepG2 cells. Inhibition of autophagosome formation with siRNA against Atg5 attenuated CIT-induced lysosomal membrane permeabilization. In addition, CIT induced collapse of mitochondrial transmembrane potential as assessed by JC-1 staining. Furthermore, caspase-3 activity assay showed that CIT induced apoptosis in HepG2 cells. Inhibition of autophagosome formation attenuated CIT-induced apoptosis, indicating that CIT-induced apoptosis was autophagy-dependent. Cathepsin D inhibitor, pepstatin A, relieved CIT-induced apoptosis as well, suggesting the involvement of the lysosomal-mitochondrial axis in CIT-induced apoptosis. Taken together, our data demonstrated that CIT induced autophagy-dependent apoptosis through the lysosomal-mitochondrial axis in HepG2 cells. The study thus provides essential mechanistic insight, and suggests clues for the effective management and treatment of CIT-related diseases.
[Show abstract][Hide abstract] ABSTRACT: An imbalance of oxidation and antioxidation is one of the primary causes of atherosclerosis. The use of natural plant compounds with effects has been proven to have clinical relevance. 6-Gingerol, one of the major components of ginger, has diverse pharmacologic effects. In this study, the chemoprotective effect of 6-gingerol against hydrogen peroxide-induced DNA damage in human umbilical vein endothelia cells (HUVECs) was investigated. The comet assay was used to monitor DNA strand breaks. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). Our data revealed that 6-gingerol significantly reduced the DNA strand breaks caused by hydrogen peroxide. 6-Gingerol effectively suppressed hydrogen peroxide-induced intracellular ROS formation. The GSH depletion in HUVECs was also attenuated by 6-gingerol pretreatment. Moreover, lysosomal membrane stability was destroyed and mitochondrial membrane potential decreased after treated by hydrogen peroxide. Those effects can be protected by 6-gingerol. These firmly indicate 6-gingerol has a strong protective ability against the DNA damage caused by hydrogen peroxide in HUVECs, and the mechanism may relate to the antioxidant activity. Our data suggest 6-gingerol may be beneficial in the prevention of atherosclerosis.
Food Science and Technology Research 09/2014; 20(5):947-954. DOI:10.3136/fstr.20.947 · 0.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Iron deficiency (ID) anemia (IDA) alters auditory neural normal development in the mammalian cochlea. Previous results suggest that mild maternal IDA during pregnancy and lactation altered the hearing and nervous system development of the young offspring, but the mechanisms underlying the association are incompletely understood. The objective of this study was to evaluate the role of apoptosis in the development of sensory hair cells following mild maternal IDA during pregnancy and lactation. We established a maternal anemia model in female guinea pigs by using a mild iron deficient diet. The offspring were weaned on postnatal day (PND) 9 and then was given the iron sufficient diet. Maternal blood samples were collected on gestational day (GD) 21, GD 42, GD 63 and PND 9, serum level of iron (SI) or hemoglobin (Hb) was measured. Blood samples of pups were collected on PND 9 for SI measurement. On PND 24, pups were examined the distortion product otoacoustic emission (DPOAE) task, and then the cochleae were harvested for assessment of apoptosis by immunohistochemistry of cysteine-aspartic acid proteases 3/9 (caspase-3/9) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and by double immunofluorescence for the colocalization of TUNEL and caspase-3. Blood samples of pups were collected on PND 24 for SI and Hb measurements. Here we show that mild maternal IDA during pregnancy and lactation resulted in hearing impairment, decreased hair cell number, caspase-3/9 activation and increased apoptotic cell number of young guinea pigs. These results indicate a key role for apoptosis in inhibition of hair cell development, caused by mild maternal IDA during pregnancy and lactation.
[Show abstract][Hide abstract] ABSTRACT: Arsenic exposure can result in damages of the neurological system. The present study aimed at whether cell proliferation and neurogenesis in the adult mouse hippocampus were affected after arsenic exposure and whether they could recover after exposure cessation. Mice were randomly placed into 3 groups. The first group received distilled water alone for 4 months (control group); the second group received 4.0mg/L As(2)O(3) through drinking water for 4 months (arsenic group); the third group received 4.0mg/L As(2)O(3) for 2 months and then changed to distilled water for another 2 months (recovery group). Serum and cerebrum arsenic concentrations of the arsenic group were significantly elevated, and then decreased to normal after the change of arsenic to water in the diet. After a four-month administration, the hippocampal number of proliferative cells and the percentage of new mature neurons decreased in the arsenic group as compared with the control group, however, increased significantly in the recovery group when compared with the arsenic group, and restored to the control level. There were no significant differences for apoptosis in different groups. Obvious histopathological ameliorations were observed in the hippocampus of the recovery group. The inhibition of hippocampus cell proliferation and neurogenesis by arsenic is reversible after the arsenic administration was terminated.
[Show abstract][Hide abstract] ABSTRACT: Patulin (PAT) is a mycotoxin produced by several Penicillium, Aspergillus and Byssochlamys species. Since PAT is a potent genotoxic compound, and PAT contamination is common in fruits and fruit products, the search for newer, better agents for protection against genotoxicity of PAT is required. In this study, the chemoprotective effect of 6-gingerol against PAT-induced genotoxicity in HepG2 cells was investigated. The comet assay and micronucleus test (MNT) were used to monitor genotoxic effects. To further elucidate the underlying mechanisms, the intracellular generation of reactive oxygen species (ROS) and level of reduced glutathione (GSH) were tested. In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG). The results showed that 6-gingerol significantly reduced the DNA strand breaks and micronuclei formation caused by PAT. Moreover, 6-gingerol effectively suppressed PAT-induced intracellular ROS formation and 8-OHdG level. The GSH depletion induced by PAT in HepG2 cells was also attenuated by 6-gingerol pretreatment. These findings suggest that 6-gingerol has a strong protective ability against the genotoxicity caused by PAT, and the antioxidant activity of 6-gingerol may play an important part in attenuating the genotoxicity of PAT.
Phytotherapy Research 10/2011; 25(10):1480-5. DOI:10.1002/ptr.3446 · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 6-gingerol, a major component of ginger, has antioxidant, anti-apoptotic, and anti-inflammatory activities. However, some dietary phytochemicals possess pro-oxidant effects as well, and the risk of adverse effects is increased by raising the use of doses. The aim of this study was to assess the genotoxic effects of 6-gingerol and to clarify the mechanisms, using human hepatoma G2 (HepG2) cells. Exposure of the cells to 6-gingerol caused significant increase of DNA migration in comet assay, increase of micronuclei frequencies at high concentrations at 20-80 and 20-40 microM, respectively. These results indicate that 6-gingerol caused DNA strand breaks and chromosome damage. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis on 8-hydroxydeoxyguanosine (8-OHdG). Results showed that lysosomal membrane stability was reduced after treatment by 6-gingerol (20-80 microM) for 40 min, mitochondrial membrane potential decreased after treatment for 50 min, GSH and ROS levels were significantly increased after treatment for 60 min. These suggest 6-gingerol induces genotoxicity probably by oxidative stress; lysosomal and mitochondrial damage were observed in 6-gingerol-induced toxicity.
[Show abstract][Hide abstract] ABSTRACT: Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress.
[Show abstract][Hide abstract] ABSTRACT: This paper investigates concentrations of various heavy metals in ambient particulate matter (PM) and provide evidence for
prevention from air pollution. The concentrations of heavy metal components in the PM were determined by inductively coupled
plasma/Mass spectrometry (ICP/MS) from September 2000 to August 2002 in a northeast industrial city in China. Concentrations
of Cd, Mn, Pb, Ni, Cr and As in the PM were 9.3, 461.9, 588.7, 69.5, 205.7 and 57.4 ng/m3 in the industrial area, and 5.7, 245.5, 305.0, 31.4, 58.8 and 32.5 ng/m3 in the main road, respectively. Concentrations of these heavy metals except Cd were significantly higher in the industrial
area and main road than those in the suburban area (P < 0.05 or P < 0.01). The change curves of the six heavy metal concentrations show their concentrations increased in the winter and spring,
but decreased in the summer and autumn. The results indicate that concentrations of the metals in the PM are relatively high
in the industrial area and main road.
Frontiers of Medicine in China 06/2008; 2(2):207-210. DOI:10.1007/s11684-008-0040-z
[Show abstract][Hide abstract] ABSTRACT: In order to investigate the effects of Zn on Pb toxicities. Proportion of abnormal sperm, percentage of micronucleated polychromatic erythrocyte (MPCE), serum thyroid hormones (T(3), T(4)) and cortisol were measured. Rats received intraperitoneal injection of 25 mg/kg Pb acetate, 4 mg/kg Zn acetate, both Pb acetate and Zn acetate, or normal saline as controls, once every two days, 7 times in total. No significant differences in whole blood Pb were detected between groups received Pb alone or both Pb and Zn. On the contrary, the concentration of whole blood Zn in the group given Zn alone was significantly higher than that in the group that received both Pb and Zn. In the groups given Pb alone or both Pb and Zn, proportion of abnormal sperm, frequency of MPCE and serum cortisol were significantly higher than those in controls, whereas serum T(3) and T(4) were significantly lower than in controls. In the group given both Pb and Zn, T(4) was decreased most obviously among the four groups. While the proportion of abnormal sperm was less in the group given both Pb and Zn than in the group given Pb alone. These findings suggest that Zn coadministration might alleviate toxic effects of Pb on the male reproductive system, whereas it could enhance the toxicity on thyroid function. Zn did not affect the toxicities of Pb on cytogenetic systems as indicated by MPCE percentage, and on serum cortisol levels under the dose of the present study. Our results suggested the double-edged effects of Zn on Pb toxicities in different organs. Therefore, the effects of Zn on Pb toxicities should be evaluated systematically.
Industrial Health 09/2007; 45(4):546-51. DOI:10.2486/indhealth.45.546 · 1.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the concentrations and distributions of urinary arsenic (As) metabolites in 233 residents exposed to 20, 90, or 160 microg/L inorganic arsenic (iAs) in drinking water from three villages in Hohhot, Inner Mongolia, China, that formed one control and two exposed groups.
We used hydride generation-atomic absorption spectrometry (HGAAS) to determine iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA).
The concentrations of each urinary As species in the two exposed groups were significantly higher than in the control group for both children and adults. Both children and adults in exposed groups had higher percent iAs and MMA and lower percent DMA, and low primary and secondary methylation indices (PMI and SMI, respectively) than those in the control group. However, children showed significant increases in percent DMA and the SMI as well as decreases in the percent MMA when the iAs exposure level increased from 90 to 160 microg/L. In addition, children in the two exposed groups showed lower percent MMA but higher percent DMA and higher SMI than adults in the same exposed group. No significant differences in As metabolite concentrations and distributions were found between males and females in each group. A significant correlation was also found in the SMI between 11 pairs of children and their mothers from the 160-microg/L-exposed group.
Children had higher a capacity for secondary methylation of As than adults when exposed to the same concentrations of iAs in drinking water. Exposure to As may increase the capacity for methylation in children to some extent.
Environmental Health Perspectives 05/2007; 115(4):648-52. DOI:10.1289/ehp.9271 · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this research work is to study the effects of sodium arsenite on activity, mRNA and protein expression of catalase (CAT) in established human cell lines of keratinocytes (HaCaT). Based on the AlamarBlue assay, we found that a high level (100 micromol/l) of sodium arsenite inhibited cell viability. The reactive oxygen species (ROS) content in cells was increased in all treated cultures dose-dependently. CAT activity, mRNA expression and protein levels were decreased by 5-20 micromol/l of sodium arsenite. It is highly suggestive that CAT gene expression and protein levels are affected by arsenic.
Toxicology in Vitro 11/2006; 20(7):1139-44. DOI:10.1016/j.tiv.2006.02.008 · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To learn the effect of cigarette smoke solution (CSS) on viability of rat lymphocytes and the intervention of antioxidants.
CSS was prepared by bubbling main-stream cigarette smoke into PBS, then 0.1 x 10(-3) cig/ml, 2 x 10(-3) cig/ml, 4 x 10(-3) cig/ml, 8 x 10(-3) cig/ml, 12 x 10(-3) cig/ml, 16 x 10(-3) cig/ml CSS were added into 7 groups of rat lymphocytes respectively. Alamar blue was added to each group 2 hours later, and after another 4 hours reduction rate of Alamar blue was detected and used to evaluate viability of cells. Otherwise, pretreated with vitamin C (VC), vitamin E(VE), glutathione(GSH), melatonin(MLT) or dimethyl sulfoxide(DMSO), cells were treated with 8 x 10(-3) cig/ml CSS and reduction rates of Alamar blue were detected as before.
Alamar blue reduction rates in 2 x 10(-3) cig/ml - 16 x 10(-3) cig/ml groups were lower than that of control significantly, and there was a dose-effect relationship. Also, Alamar blue reduction rates increased in CSS-groups pretreated with 0.05 mmol/LVC, 0.2 mmol/LVE, 0.1 mmol/LMLT, 1 mmol/LGSH or 1% DMSO.
Viability of rat lymphocytes decreased in the presence of CSS, and it could be antagonised by antioxidants such as vitamin C, vitamin E, glutathione, melatonin and dimethyl sulfoxide.
Wei sheng yan jiu = Journal of hygiene research 06/2004; 33(3):300-2.
[Show abstract][Hide abstract] ABSTRACT: To explore whether there is difference in arsenicals-induced DNA damage of human lymphocyte.
Lymphocyte were sterilely collected from healthy donor and exposed to sodium arsenite (AsIII), sodium arsenate(AsV) and methyl sodium arsenate(MAsv) at 1,5,10,20 and 50 mumol/L. After incubation of 24 hours, cells were collected by centrifugation and DNA damage was detected by single cell gel electrophoresis (SCGE).
The comet frequency distribution of all groups except 1 mumol/L group of MAsV were significantly different from that of control. The comet length of all groups except 1 mumol/L group of AsV and 1.5 mumol/L groups of MAsV were significantly higher than that of control. There were correlations between the doses of arsenicals and the ratios of comet cell or length of comet(rAsIII = 0.8134, rAsV = 0.8734, rMAsV = 0.8994).
DNA damage in human lymphocyte were induced by all the three arsenicals. A dose-effect relationship was observed between exposure doses of the same arsenical and DNA damage. With different arsenicals but the same exposure dose, the DNA damage level was as follow: AsIII > AsV > MAsV.
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 10/2002; 20(5):327-30.