ABSTRACT
OBJECTIVE@#This study was conducted to investigate the regulation of endoplasmic reticulum stress on Nrf2 signaling pathway in the kidneys of rats.@*METHODS@#Rats were divided into twelve groups of six animals each. Some groups were pre-administered with bacitracin or tauroursodeoxycholic acid (TUDCA), and all of them were treated with 5-20 μmol/kg cadmium (Cd) for 48 h. The oxidative stress levels were analyzed using kits. The mRNA and protein expression levels of endoplasmic reticulum stress-related factors and Nrf2 signaling pathway-related factors were determined using RT-PCR and western blot.@*RESULTS@#Cd exposure resulted in oxidative stress in the kidneys of rats and upregulated the expression of endoplasmic reticulum stress (ERS)-related factors and Nrf2 signaling pathway-related factors, especially at doses of 10 and 20 μmol/kg Cd, and the expression changes were particularly obvious. Moreover, after pretreatment with bacitracin, Cd upregulated the expression of ERS-related factors to a certain extent and, at higher doses, increased the mRNA expression of Nrf2. After pretreatment with TUDCA, Cd reduced the level of ERS to a certain extent; however, at these doses, there were no significant changes in the expression of Nrf2.@*CONCLUSION@#Cadmium can result in ERS and oxidative stress in the kidneys of rats, activate Nrf2, and upregulate the transcriptional expression of phase II detoxification enzymes under these experimental conditions. ERS has a positive regulation effect on Nrf2 signaling pathway but has little effect on the negative regulation of Nrf2 signaling pathway in cadmium toxicity.
Subject(s)
Animals , Female , Male , Cadmium , Toxicity , Endoplasmic Reticulum Stress , Environmental Pollutants , Toxicity , Kidney , Metabolism , NF-E2-Related Factor 2 , Genetics , Metabolism , Oxidative Stress , Rats, Sprague-Dawley , Signal Transduction , Taurochenodeoxycholic Acid , PharmacologyABSTRACT
OBJECTIVE: To explore the effects of cadmium chloride( CdCl_2) on DNA single strand breaks and the production of 8-hydroxy-2'-deoxyguanosine( 8-OHdG) in human embryonic kidney epithelial cells( HEK cells). METHODS: HEK cells in logarithm growth phase were divided into 5 groups and incubated with the different concentrations of CdCl_2( 0. 0,2. 5,5. 0,10. 0 and 20. 0 μmol/L) for 24,48 and 72 hours in vitro. After harvesting the cells,DNA single strand breaks was tested by single cell gel electrophoresis,and the level of 8-OHdG was measured using the enzyme linked immunosorbent assay. RESULTS: The Olive tail moment was statistically significant in the main effect of CdCl_2 exposed HEK cells( P < 0. 01). Among them,when HEK cells were exposed to 5. 0 μmol / L of CdCl_2,the Olive tail moment began to have a statistical significant increasing trend compared with the 0. 0 μmol / L group( P < 0. 05); when CdCl_2 concentration was 2. 5-10. 0 μmol / L,the Olive tail moment lengthened with the increasing dose of cadmium exposure,showing a doseeffect relationship( P < 0. 05). The tail DNA% was statistically significant in the interaction between exposure treatment and exposure time in HEK cells( P < 0. 01). Among them,when CdCl_2 concentration was at 2. 5-10. 0 μmol / L at 24 hours time point and 5. 0-20. 0 μmol / L at 48 hours time point,the tail DNA% raised with the increasing dose of cadmium exposure,showing a dose-effect relationship( P < 0. 05). The tail DNA% at 3 time points of 24,48 and 72 hours after exposure to 20. 0 μmol / L of CdCl_2 in HEK cells increased with the increasing time of cadmium exposure,showing a timeeffect relationship( P < 0. 05). The level of 8-OHdG had statistical significance in the main effect of CdCl_2 exposure treatment in HEK cells( P < 0. 05). Among them,the level of 8-OHdG was first significantly increased only after exposure to 10. 0 μmol / L CdCl_2 compared with the 0. 0 μmol / L group( P < 0. 05). After treatment with Ca Cl2,there was no doseeffect relationship and time-effect relationship found between the cadmium chloride exposure and tail length as well as the tail / head length ratio and 8-OHdG level. CONCLUSION: To a certain extent,CdCl_2 exposure may cause both DNA single strand breaks and 8-OHdG production in HEK cells. Compared with 8-OHdG,the DNA single strand breaks show more significant change with a lower dose of cadmium treatment,which may be related to its higher sensitivity to cadmium toxicity than 8-OHdG.
ABSTRACT
OBJECTIVE: To establish a methodology for determining indium in human whole blood,serum and urine by inductively coupled plasma-mass spectrometry( ICP-MS). METHODS: The whole blood,serum and urine samples were diluted 10 times in 0. 01%( mass fraction) Triton X-100 plus 0. 50%( mass fraction) nitric acid solution,and the indium level was determined by ICP-MS. Rhodium standard solution was used as the internal standard control. RESULTS: The working curve obtained from measurement of whole blood,serum and urine of normal individuals was compared to the standard curve and showed no significant difference in quantitative analysis( P > 0. 05). The linearity range of indium concentration in whole blood,serum and urine was 0. 000-20. 000 μg / L,and all the correlation coefficients were greater than 0. 999 with a detection limit of 0. 144 μg / L. The recovery rates of whole blood,serum and urine were 87. 90%-95. 92%,91. 50%-94. 20% and 90. 40%-96. 57%,respectively. The relative standard deviations( RSDs) of within-run precision were 3. 81%-7. 05%,3. 75%-5. 90% and 4. 31%-6. 62%,respectively. The RSDs of between-run precision were 2. 90%-7. 10%,3. 80%-5. 92% and 4. 16%-5. 94%,respectively. Samples could be stored for at least 14 days under the temperature of- 20 ℃. The indium in whole blood,serum and urine of workers occupationally exposed to indium( exposure group,135 person-time) and control group workers( 120 person-time) were examined. Indium was detected for 17 person-time in whole blood and serum in the exposure group with a detection rate of 1. 26%. Indium was not detected in urine samples in exposure group. It was not detected in all samples in control group. CONCLUSION: This methodology has features of simple operation,high accuracy and good precision,which is suitable for the accurate quantitative analysis of indium in biological samples.
ABSTRACT
OBJECTIVE: To explore an improved method for determination of cyclohexane and methylcyclohexane in workplace air by solvent desorption-gas chromatography. METHODS: Cyclohexane and methylcyclohexane in workplace air were collected by activated carbon tubes,desorbed with carbon disulfide,separated by DB-1 capillary chromatography column,detected by flame ionization detector and quantified using the standard calibration curves. RESULTS: The linear range of the concentration of cyclohexane and methylcyclohexane were 1. 0-1 402. 2 and 0. 8-1 999. 4 mg / L respectively.Both the correlation coefficients were 0. 999 9. Both the detection limits were 0. 3 mg / L. The limits of quantification were1. 0 and 0. 8 mg / L respectively. Both the minimum detectable concentrations were 0. 2 mg / m3. The minimum quantitative mass concentrations of cyclohexane and methylcyclohexane were 0. 7 and 0. 6 mg / m3respectively( sample volume was 1. 5L). The average desorption efficiencies were 98. 5%-99. 3% and 97. 6%-99. 0% respectively. The relative standard deviations( RSD) of within-run precision were 0. 36%-0. 59% and 0. 34%-0. 50% respectively. The RSD of between-run precision were 0. 89%-2. 04% and 0. 87%-2. 22% respectively. The samples could be stored for up to 7 days at room temperature. CONCLUSION: This method has features of simple operation,high sensitivity and good precision,which is suitable for simultaneous determination of cyclohexane and methylcyclohexane in workplace air.