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OBJECTIVE: To investigate the role of nuclear factor erythroid-2-related factor 2(NRF2) signaling pathway in trichloroethylene(TCE) induced oxidative stress in human liver cancer HepG2 cells. METHODS: HepG2 cells in the exponential growth phase were randomly divided into control group and low-, medium-and high-dose groups, and the cells were stimulated with TCE at the final concentrations of 0, 2, 4 or 8 mmol/L respectively for 24 hours. After TCE exposure, the cells were collected. The activity of superoxide dismutase(SOD) was measured by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphenyl)-2 h-tetrazole monosodium salt method.The activities of catalase(CAT) and glutathione peroxidase(GSH-Px) were detected by enzymatic method. The level of malondialdehyde(MDA) was detected by thiobarbituric acid method. The level of 8-hydroxydeoxyguanosine(8-OHDG) was detected by enzyme-linked immunosorbent assay. The mRNA expression of NRF2, heme oxygenase(HO1), glutamate-cysteine ligase catalytic subunit(GCLC), NAD(P) quinone oxidoreductase 1(NQO1) were detected by real-time polymerase chain reaction and the protein expression of NRF2, HO1, GCLC, NQO1 were detected by Western blotting. RESULTS: The activity of CAT in HepG2 cells decreased in the 3 doses drug exposure groups(all P<0.05). The activity of GSH-Px increased(all P<0.05), while the level of MDA in HepG2 cells decreased in low-dose group compared with the control group(P<0.05). There was no statistical significance in SOD activity and 8-OHDG level of HepG2 cells among these 4 groups(all P>0.05). The mRNA and protein relative expression of NRF2 and GCLC in HepG2 cells decreased in the low-and medium-dose groups(all P<0.05) compared with the control group. The mRNA relative expression of HO1 decreased(all P<0.05). The HO1 protein relative expression of HepG2 cells increased in low-dose group compared with the control group(P<0.05). The mRNA and protein relative expression of NQO1 in low-dose group increased(both P<0.05). The protein relative expression of HO1 in HepG2 cells in medium-dose group was lower than that in control group(P<0.05).The mRNA and protein relative expression levels of NRF2 and NQO1 increased in HepG2 cells of high-dose group(all P<0.05) and the mRNA relative expression of HO1 increased in HepG2 cells of high-dose group(all P<0.05) compared with the other 3 groups. CONCLUSION: The low and medium dose TCE stimulation can cause oxidative stress in HepG2 cells and decrease the antioxidant enzyme activity. The high dose TCE stimulation to HepG2 cells can activate NRF2 signaling pathway, thus upregulating the expression of downstream antioxidant enzymes HO1, GCLC and NQO1, and relieving the oxidative damage caused by TCE.
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OBJECTIVE: To explore the influencing factors of occupational stress from occupational hazards in employees of a power grid enterprise. METHODS: A total of 972 employees from 3 substations and 1 power dispatch center of a power grid enterprise were selected as research subjects by the cluster sampling method. The Chinese version of the Job Content Questionnaire was used to evaluate the occupational stress using the job demand control(JDC) model. The influence of occupational hazards on occupational stress was analyzed. RESULTS: The median, the 25 th and 75 th percentile scores [M(P_(25), P_(75))] of the 972 research subjects on job demand, job control, and social support dimensions of JDC model occupational stress were 14(12, 15), 25(23, 26), 24(23, 24), respectively. The M(P_(25), P_(75)) of the demand/control(D/C) ratio was 0.99(0.89, 1.13). The incidence of occupational stress was 48.4%(470/972) by the JDC model. The job demand dimension scores, D/C ratios, and incidence of occupational stress by JDC model were higher in employees exposed to electromagnetic radiation, high temperature, high altitude, and visual display terminal(VDT) than in those employees not exposed to the above factors(all P<0.05). The results of multivariate logistic regression analysis showed that the risk of occupational stress increased in those employees exposed to high temperature, high altitude and VDT(all P<0.05) after excluding the influence of confounding factors such as age, length of service, monthly income and exercise. The odds ratio and 95% confidence intervals were 1.91(1.43-2.54) and 1.67(1.26-2.21), respectively. CONCLUSION: The level of occupational stress among employees in power grid enterprise is relatively high by JDC model. High-temperature, high-altitude and VDT operation are the main risk factors of occupational stress by JDC model.
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OBJECTIVE: To study the effect of aquaporin 4(AQP4) in regulating the permeability of blood-brain barrier(BBB) induced by subacute 1,2-dichloroethane(1,2-DCE) inhalation. METHODS: Specific pathogen free healthy CD-1 male Aqp4 genetically engineered mice(Aqp4~(+/+)and Aqp4~(-/-)) were randomly divided into control and low-, medium-and high-dose groups. The mice were exposed to 1,2-DCE at the dosages of 0.00, 100.00, 350.00 and 700.00 mg/m~3 for 6 hours per day for consecutive 28 days by systemic dynamic inhalation. After the end of 1,2-DCE exposure, the BBB permeability was evaluated by Evans blue staining. Real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of genes related to BBB tight junction protein(Tjp)1, Tjp2, Tjp3, claudin(Cldn)3, Cldn5, Cldn11, occludin(Ocln), matrix metalloproteinase(Mmp)2, Mmp9 and Na-K-Cl cotransporter-1(Nkcc1). RESULTS: The BBB permeability in mice showed significant change with 1,2-DCE dose and Aqp4 genotype(P<0.01). The BBB permeability of Aqp4~(+/+) genotype mice was higher in low-, medium-and high-dose groups than that of control group(all P values were <0.05). The permeability of BBB was lower in Aqp4~(+/+) genotype mice in the control group than that of Aqp4~(-/-) genotype mice in the same group(P<0.05), but BBB permeability was higher in Aqp4~(+/+) genotype mice in the three dose groups than that of Aqp4~(-/-) genotype mice in the same group(all P values were <0.05). The Cldn3 and Olcn mRNA relative expression in the brain cortex had statistical difference in mice with different genotype(all P values were <0.01). The mRNA relative expressions of Cldn3 and Olcn in the brain cortex were higher in Aqp4~(-/-) genotype mice than that of Aqp4~(+/+) genotype mice(all P values were <0.01). The relative mRNA expression levels of Tjp1, Tjp2, Tjp3, Cldn5, Cldn11, Mmp2, Mmp9 and Nkcc1 in the cerebral cortex of mice were not statistically significant in aspect of 1,2-DCE exposure dose and genotype(all P values were >0.05). CONCLUSION: Exposure to 1,2-DCE can increase BBB permeability in mice, and the mechanism may be associated with 1,2-DCE-induced down-regulation of Aqp4 and up-regulation of mRNA expression of the cerebral cortex TJP-related molecules Cldn3 and Ocln.
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OBJECTIVE: To investigate the effect of n-hexane on the level of sex hormones and expression of estrogen receptor(ER) in rats and the protective effect of Lyciumbarbarum polysaccharide(LBP) on n-hexane-induced reproductive toxicity. METHODS: Based on factorial design model of 4×2, specific pathogen free adult female SD rats were divided into control group and low-, medium-and high-n-hexane exposure groups, and each group was divided into non-LBP intervention and LBP intervention sub-group. There were 8 subgroups with 6 rats in each group. On the first day, the rats in the 4 groups were given intraperitoneal injection of n-hexane at 0, 675, 1 350 and 2 700 mg/kg body weight, respectively. On day 2-4, the rats in the non-LBP intervention subgroup were given intragastric administration of 0.9% sodium chloride solution, and the rats in the LBP intervention subgroup were given intragastric administration of LBP at 50 mg/kg body weight once a day. On the fifth day, all animals were sacrificed, and the levels of follicle stimulating hormone(FSH), luteinizing hormone(LH), estradiol, progesterone were detected by enzyme linked immunosorbent assay. The mRNA expression of Erα, Erβ and G protein coupled estrogen receptor 1(Gper1) was detected by real time fluorescence polymerase chain reaction, and the expression of ERα, ERβ and GPER1 protein was detected by Western blotting. RESULTS: i) In the absence of LBP intervention(i.e. simple n-hexane exposure), there was no significant difference in the level of serum FSH, LH, estradiol and progesterone in the 4 groups(P>0.05). The relative expression of Erβ mRNA in ovary of low dose group decreased, while the relative expression of proteins of ERα and GPER1 increased(P<0.05) when compared with the control group. The relative expression of Erα mRNA and GPER1 protein in the ovary of medium-and high-dose groups increased(P<0.05), while the relative expression of Erβ, Gper1 mRNA and ERβ protein decreased(P<0.05). The relative expression of ERα protein in ovary of high-dose group increased(P<0.05). ii) At the same dose of n-hexane exposure, the relative expression of Erα mRNA in ovary of rats in low dose group increased(P<0.05), while the relative expression of ERβ and GPER1 protein decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). The relative expression of ERα and GPER1 protein in ovary of medium dose group increased(P<0.05), while the relative expression of Gper1 mRNA and GPER1 protein in ovary of high dose group decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). CONCLUSION: n-Hexane can up-regulate the expression of ERα and GPER1 in rat ovary, but has no significant effect on female endocrine system. LBP may play a protective role in female reproductive system by up-regulating the expression of ERα and GPER1.
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OBJECTIVE: To observe the effect of n-hexane subchronic exposure on the serum level of neuron specific enolase(NSE), neurofilament light chain protein(NF-L) and nerve growth factor(NGF) in rat, and to explore the feasibility of using NSE, NF-L and NGF as biomarkers of n-hexane neurotoxicity. METHODS: Specific pathogen free male SD rats were randomly divided into control group and low-, medium-and high-dose exposure groups, with 6 rats in each group. Rats in the low-, medium-and high-dose exposure groups were given n-hexane solution at doses of 168, 675 and 2 700 mg/kg body mass, respectively, while rats in the control group were gavaged with 0.9% sodium chloride solution, once a day, 5 days a week for 6 weeks. At week 0, 2, 4, and 6 of exposure, the body mass of the rats was weighed, the gait scores were performed, and the serum levels of NSE, NF-L, and NGF were detected.RESULTS: Body mass, gait score and serum levels of NSE and NF-L in rats were statistically significant in terms of the n-hexane exposure dose and exposure time(P<0.01). At the 6 th week of n-hexane exposure, the body mass of the three dose exposure groups was lower than that of the control group(P<0.05), and the gait score was higher than that of the control group(P<0.05). Moreover, the abnormal gait of the rats showed a dose-effect relationship with the increasing n-hexane poisoning dose. At week 2, 4 and 6, the serum levels of NSE and NF-L in these three dose exposure groups were higher than that in the control group(P<0.05). In addition, the serum level of NF-L in rats in the medium-and high-dose exposure groups increased with the n-hexane exposure time increasing and showed a time-effect relationship(P<0.05). The level of serum NGF in rats was statistically significant in the main effects of n-hexane dose and duration of exposure(P<0.05). The serum NGF level in the high-dose exposure group was lower than that in the control group, the low-dose and medium-dose exposure groups(P<0.05). NGF level in serum of rats at week 6 was lower than that at week 0, 2 and 4(P<0.05). CONCLUSION: Both NSE and NF-L in serum can be used as biomarkers for the early effect of n-hexane on peripheral nerve injury. The feasibility of using serum NGF as a biomarker for the early effect of n-hexane on peripheral nerve injury warrants further investigation.
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OBJECTIVE: To analyze the influencing factors of suspected occupational noise-induced deafness( ONID) in noise-exposed workers. METHODS: A total of 38 770 noise-exposed workers engaged in occupational health examination were collected as the study subjects from 2012-2016 by judgment sampling method. The data of workers' occupational medical examination was collected,and the incidence and influencing factors of suspected ONID were analyzed. RESULTS: A total of 125 cases of suspected ONID were detected and the detection rate was 0. 32%. The result of multivariate Logistic regression showed that male workers exposed to noise had a higher risk of suspected ONID than female workers( P <0. 01). The odds ratio( OR) and 95% confidence interval( CI) were 1. 98( 1. 22-3. 19). The older the age and the longer service length of workers exposed to noise,the higher the risk of suspected ONID( P < 0. 01). The ORs and 95% CIs were 1. 79(1. 43-2. 25) and 1. 84( 1. 47-2. 30) respectively. The noise-exposed workers had a higher risk of suspected ONID in foreign-funded enterprises than domestic-funded enterprises( P < 0. 01). The noise-exposed workers had a higher risk of suspected ONID in metal manufacturing industries than in non-metal manufacturing industries( P < 0. 01). The ORs and 95% CIs were 1. 83(1. 19-2. 82) and 2. 02(1. 40-2. 94) respectively. CONCLUSION: The incidence of suspected ONID is affected by factors of gender,age,length of service,economy type of enterprises and industry type.
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OBJECTIVE: To study the effects of cadmium on the expression of estrogen receptor( ER) and miRAN-155,miRAN-200 c in human breast cancer MCF-7 cells. METHODS: MCF-7cells in logarithmic growth phase were randomly divided into fulvestrant( ICI182780,ICI) group and non-ICI group. The non-ICI group was treated with cadmium chloride(Cd Cl2) at the final concentrations of 0. 0,2. 5,5. 0 and 10. 0 μmol/L for 24 hours. The ICI group was pretreated at a concentration of 1. 0 μmol/L for 12 hours,and then treated with Cd Cl2 at the final concentrations 0. 0,2. 5,5. 0 and 10. 0μmol/L for 24 hours. The cell proliferation activity was measured by methyl thiazolyl tetrazolium assay. Flow cytometry was used to measured cell apoptosis. Western blot was applied to measure the relative expression of ERα and ERβ protein,and the relative expression of miRNA-155 and miRNA-200 c were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS: The proliferation rates of MCF-7 cells in 2. 5,5. 0 and 10. 0 μmol/L Cd Cl2 groups were significantly decreased than the 0. 0 μmol/L Cd Cl2 group( P < 0. 05). The proliferation rate in ICI group was lower than that of the non-ICI group( P < 0. 05). When Cd Cl2 concentration was 2. 5,5. 0 and 10. 0 μmol/L,the apoptosis rate of MCF-7 cells in non-ICI group increased compared with those cells without exposure to Cd Cl2( P < 0. 05). The relative expression of ERα,ERβ,miRNA-155 and miRNA-200 c increased( P < 0. 05). The proliferation of MCF-7 cells in ICI group decreased( P < 0. 05),and the relative apoptosis rate increased( P < 0. 05); and the relative expression of ERαand ERβ increased( P < 0. 05),the relative expression of miRNA-155 and miRNA-200 c decreased( P < 0. 05). When treated without Cd Cl2,the apoptosis rate of the ICI group increased compared with non-ICI group(P < 0. 05),the relative expression of ERα and ERβ decreased( P < 0. 05),and the relative expression of miRNA-155 and miRNA-200 c were increased( P < 0. 05). When Cd Cl2 concentration was 2. 5,5. 0 and 10. 0 μmol/L,the apoptosis rate and the relative expression of ERα,ERβ,miRNA-155 and miRNA-200 c decreased compared with the non-ICI group treated with same dose Cd Cl2(P < 0. 05). CONCLUSION: Cadmium can induce cell apoptosis and increase expression of miRNAs through the ER signaling pathway.
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This study investigated the effect of cadmium on the telomerase activity, the expression of TERT, c-myc and p53 and the apoptosis of rat hepatocytes. The rats were administrated 5, 10 and 20 μmol/kg cadmium chloride intraperitoneally and sacrificed 48 h after the initial treatment. The telomerase activity of the rat hepatocytes was measured by the telomeric repeat amplification protocol (TRAP), and apoptosis was detected by flow cytometry. The mRNA expressions of TERT, c-myc and p53 were measured by reverse transcription-polymerase chain reaction (RT-PCR). C-myc and P53 proteins were determined by immunochemistry. The results showed that cadmium chloride increased the hepatocellular telomerase activity in a dose-dependant manner and induced the apoptosis of hepatocytes significantly. The value of relative coefficient between the telomerase activity and the apoptosis rate was 0.9398. RT-PCR revealed that specific bands corresponding to the TERT mRNA, c-myc mRNA, and p53 mRNA were displayed at 185, 342 and 538 bp respectively. Cadmium chloride could substantially increase the mRNA expressions of TERT, c-myc and p53 in rat hepatocytes, as compared with control. Moreover, cadmium chloride at the doses of 5, 10 and 20 μmol/kg could increase the content of P53 protein in rat hepatocytes obviously, but only that at the doses of 10 and 20 μmol/kg substantially promoted the c-myc protein level in rat hepatocytes. Our study herein suggested that cadmium may contribute to the carcinogenesis by activating telomerase, and overexpressing the mRNAs of TERT, c-myc and p53, and causing apoptosis of normal cells.
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Animals , Male , Rats , Apoptosis , Cadmium , Toxicity , Hepatocytes , Metabolism , Pathology , Proto-Oncogene Proteins c-myc , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Telomerase , Genetics , Metabolism , Tumor Suppressor Protein p53 , Genetics , MetabolismABSTRACT
This study investigated the effect of cadmium on the telomerase activity, the expression of TERT, c-myc and p53 and the apoptosis of rat hepatocytes. The rats were administrated 5, 10 and 20 μmol/kg cadmium chloride intraperitoneally and sacrificed 48 h after the initial treatment. The telomerase activity of the rat hepatocytes was measured by the telomeric repeat amplification protocol (TRAP), and apoptosis was detected by flow cytometry. The mRNA expressions of TERT, c-myc and p53 were measured by reverse transcription-polymerase chain reaction (RT-PCR). C-myc and P53 proteins were determined by immunochemistry. The results showed that cadmium chloride increased the hepatocellular telomerase activity in a dose-dependant manner and induced the apoptosis of hepatocytes significantly. The value of relative coefficient between the telomerase activity and the apoptosis rate was 0.9398. RT-PCR revealed that specific bands corresponding to the TERT mRNA, c-myc mRNA, and p53 mRNA were displayed at 185, 342 and 538 bp respectively. Cadmium chloride could substantially increase the mRNA expressions of TERT, c-myc and p53 in rat hepatocytes, as compared with control. Moreover, cadmium chloride at the doses of 5, 10 and 20 μmol/kg could increase the content of P53 protein in rat hepatocytes obviously, but only that at the doses of 10 and 20 μmol/kg substantially promoted the c-myc protein level in rat hepatocytes. Our study herein suggested that cadmium may contribute to the carcinogenesis by activating telomerase, and overexpressing the mRNAs of TERT, c-myc and p53, and causing apoptosis of normal cells.
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<p><b>OBJECTIVE</b>This study was conducted to study the effects of sodium fluoride (NaF) on rat renal apoptosis and proliferation, the antagonistic effect of selenium-zinc preparation (Se-Zn) to NaF.</p><p><b>METHODS</b>Wistar rats were provided with distilled water containing NaF (50 mg/L) and administered by gavage with different dosed of Se-Zn for six months. Kidney cell apoptosis and the cell cycle of proliferation were detected by TUNEL (TdT-mediated dUTP Nick End Labelling) and flow cytometry.</p><p><b>RESULTS</b>NaF caused rat renal apoptosis, reduce the cell number of G(2)/M period in cell cycle and decrease the relative content of DNA significantly. Se-Zn inhibited the effects of NaF on apoptosis and increased the cell number of G(2)/M period in cell cycle, but failed to increase relative content of DNA.</p><p><b>CONCLUSION</b>It was suggested that NaF could induce apoptosis and change the cell cycle in rat renal cells and Se-Zn could antagonize apoptosis and the changes of cell cycle induced by NaF.</p>
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Animals , Rats , Apoptosis , Cell Cycle , Cell Division , DNA , Genetics , Metabolism , Drug Antagonism , Flow Cytometry , In Situ Nick-End Labeling , Kidney , Pathology , Selenium , Pharmacology , Sodium Fluoride , Pharmacology , Zinc , PharmacologyABSTRACT
Objective To study the antogonistic effects of selenium(Se) on methylmercury (MeHg) induced lipid peroxidation Methods SD rats were purfused perorally with Se and MeHg The effects on lipid peroxidation in rats' brain tissue caused by MeHg and the antagonistic effects of Se were observed Results Se could reduce the accumulation levels of MeHg in brain tissue and increase the GSH contents and GSH Px activities so as to inhibit the lipid peroxidation in brain tissue induced by MeHg and reduce LPO levels Conclusion Se at a certain dose could markedly antagonize MeHg induced lipid peroxidation as a result of reducation of the accumulative levels of MeHg in brain tissue and antagonizing lipid peroxidation induced by Se itself
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To study the effects of cadmium chloride on DNA damage of rat liver cells in vivo and in vitro Single cell gel electrophoresis or Comet assay was used At the concentration of 2 185 ?mol/L, 4 375 ?mol/L, 8 75 ?mol/L, 17 50 ?mol/L, 35 00 ?mol/L, cadmium chloride could induce DNA damage of rat liver cells in vitro, and at the doses of 5 ?mol/kg, 10 ?mol/kg, 20 ?mol/kg, cadmium chloride could induce DNA damage of rat liver cells in vivo respectively The in vivo and in vitro results also showed the obvious dose response relationship between the rates of Comet cells and the doses of cadmium chloride [Conclusion]The research infered that at certain dose, cadmium could induce DNA damage and had toxic effects on rat liver cells
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Objective This study was conducted to explore the effects of fluorosis on rat renal apoptosis and proliferation, oxidative stress and necrosis. Methods Wistar rats were provided with distilled water containing NaF(50mg/L) for six months. Kidney cell apoptosis and the cell cycle of proliferation were detected by TUNEL (TdT-mediated dUTP Nick End Labelling) and flow cytometry. Rsults TUNEL_positive cells could be detected in fluoride_treated rat kidney. The apoptotic rates of fluoride_treated kidney cells were higher than that of control significantly. Fluorosis could reduce the cell number of G2/M period in cell cycle and decrease DNA relative content significantly. In addition, fluorosis could induce rat renal oxidative stress and necrosis. Cnclusion It was suggested that fluorosis could induce apoptosis and change the cell cycle of rat renal cells in vivo, and also could result in rat renal oxidative stress and necrosis.