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Objective:To determine the contents of inorganic arsenic（iAs），monomethylarsonic acid（MMA） and dimethylarsinic acid（DMA） in brain tissues and blood by using hydride generation-cold trap-atomic absorptionspectrometry（HG-CT-AAS）， and to explore the toxic effects of Realgar on central nervous system of rats. Method:The 96 Wistar rats were randomly divided into 4 groups：normal control group，0.3，0.9 and 2.7 g·kg<sup>-1</sup> Realgar groups. They then received intragastric administration for 14，28 and 42 days respectively， so a total of 12 groups were formed， with 8 animals in each group. The normal group was given the same dose of sodium carboxymethyl cellulose （CMC-Na） by gavage. The contents of iAs，MMA and DMA in blood and brain tissues were determined by HG-CT-AAS. The novel object recognition test was conducted to observe the learning and memory ability of rats. The changes of hippocampal neuron ultrastructure were observed by transmission electron microscopy. Result:There was no difference in the growth，weight and hippocampal coefficient of the experimental animals. The method of HG-CT-AAS showed a good linearity，precision，accuracy and recovery in content determination of arsenic （at various forms） in rat brain and blood. MMA and DMA were detected in the brain of realgar groups at time-dose-effect relationship. iAs，MMA and DMA were detected in the blood of Realgar groups. The nuclear membrane， mitochondria and endoplasmic reticulum in hippocampus neurons of rats were gradually damaged with the increase of Rhubarb exposure dose and time. After 14 days of exposure to Realgar，compared with the normal control group，there was no significant difference in the novel object recognition index among Realgar groups. After 28 days of exposure，only 2.7 g·kg<sup>-1</sup> Realgar group showed statistically significant difference with the control group （<italic>P</italic><0.05）. After 42 days of exposure， the novel object recognition index of 0.9 and 2.7 g·kg<sup>-1</sup> Realgar groups was significantly lower than that in normal control group（<italic>P</italic><0.05）. Conclusion:The metabolites of Realgar in rats are iAs，MMA and DMA. MMA and DMA can be accumulated in the brain tissue through the blood-brain barrier，causing the decline of the ability of learning and memory and leading to damage of hippocampal neurons.
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Objective To observe the distribution and metabolism of arsenic speciation in urine of rats exposed to different concentrations of dimethylaraenic acid (DMA) through drinking water.Methods Thrity six weaning Wistar rats were randomly divided into normal control,low-dose group and high-dose group,12 rats in each group(6 female and 6 male); average body weight of female rats was (60 ± 5)g,and male rats was (50 ± 5)g.All rats of the 3 groups were given DMA at concentrations of 0,100,200 mg/L,respectively,corresponding to their specific groups through drinking water for 10 weeks.Inorganic arsenic(iAs),monomethylarsenic acid(MMA),DMA and trimethylarsenic compound (TMA) in urine were measured by hydride generation trapping and ultrahypothermia coupled with atomic absorption spectrometry.Results After feeding for 10 weeks,the differences of rat urinary concentrations of iAs,MMA,DMA and TMA between normal control,low-dose group and high-dose group were statistically significant(x2 =25.441,25.942,25.751,17.767,all P＜ 0.01).Urinary concentrations of iAs,MMA and DMA(2.541,4.383,24.447 mg/L) of low-dose group were significant higher than those of normal control (0.784,0.000,0.743 mg/L,all P ＜ 0.05) ; iAs,MMA,DMA and TMA(3.978,7.186,35.112,4.518 mg/L) of high-dose group were significantly higher than those of normal control(0.784,0.000,0.743,0.000 mg/L,all P ＜ 0.05).The concentrations increased along with increasing doses of DMA concentrations in drinking water(all P ＜ 0.05).Conclusions After rats are exposed to DMA,most of the DMA are excreted in unchanged form in urine and a small portion of DMA is metabolized into TMA.
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Objective To study the impact of sodium arsenite(NaAsO2) exposure on melanoma cells A375 (hereinafter referred to as the A375) and G361 (hereinafter referred to as the G361) pigment production and tyrosinase (TYR) activity and the differences of pigment metabolism capacity between the cell lines.Methods A375 and G361 cells were exposed to sodium arsenite at concentrations of 0.0(control),0.1 and 1.0 μmol/L for 72hours.Cell viability was measured by Alamar Blue assay.Melanin levels and TYR activity were measured at the same time.Results After exposure for 72 hours,the cells of 0.1 μmol/L dose groups of both of the two cell lines [A375:(103.32 + 1.26)％; G361:(104.10 + 1.76)％] showed a slightincrease of proliferation without significant differences compared with those of the control[A375:(100.00 ± 1.08)％; G361:(100.00 + 1.79)％,all P ＜ 0.05] ;while cell viability of the 1.0 μmol/L dose group of both of the two cell lines[A375:(75.32 ± 1.59)％; G361:(78.26 ± 2.10)％] were significantly lower than those of the control (all P ＜ 0.05).Melanin levels of G361 cell line [(7.19 ± 0.35),(7.34 ± 0.83),(8.19 ± 0.86)pg/cell] were significantly higher than that of A375[(4.35 ± 0.72),(4.54 ± 0.01),(4.60 + 0.59)pg/cell,all P ＜ 0.05] in all the three groups.TYR activity of G361 cell line [(54.13 ± 1.21),(54.56 ± 0.21),(56.25 ± 0.85)Bq] were also markedly higher than that of A375 cell[(42.00 ±0.21),(42.90 ± 0.54),(42.91 ± 0.01)Bq,all P ＜ 0.05] in all the three groups.The melanin levels and TYR activities of both of the two cells lines showed an increase tendency along with increased doses of arsenic exposure,but without significant differences when compared with those of the three groups (all P ＞ 0.05).Conclusions Arsenic related pigment disorder may be associated with increased melanin levels and TYR activities induced by arsenic exposure; individual difference of pigment metabolism may be associated with different basal melanin levels and TYR activity between different individuals.
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ObjectiveTo study the state of oxidative injury induced by sodium arsenite(NaAsO2) in SV-40-immortalized normal uroepithelial (SV-HUC-1 ) cells.Methods SV-HUC-1 cells were exposed to different concentrations of NaAsO2[0(control),1,2,4,8,10 μmol/L] for 24 h,intracellular reactive oxygen species (ROS) was determined by flow cytometry,and the content ofintracellular nitrotyrosine(NT) and the 8-Hydroxydeoxyguanosine (8-OHdG) levels of cell culture medium were detected by enzyme linked immunosorbent assay (ELISA).Results After 24 h treatment,ROS levels(81.76 ± 4.91,95.23 ± 2.17,126.61 ± 17.95,126.74 ± 27.77,114.18 ± 9.65) of SV-HUC-1 cells in the 1,2,4,8,10 μmol/L NaAsO2 exposure groups were significantly higher than those of the control group (69.84 ± 1.28,P ＜ 0.05 or ＜ 0.01 ),ROS levels and exposure dose were positively correlated significantly(r =0.818,P＜ 0.01); the content of NT in the 10 μmol/L NaAsO2 exposure group[(919.66 ± 206.33) μg/L] was significantly higher than that in the control group[ (238.19 ± 38.28)μg/L,P ＜ 0.01 ],NT content and dye concentrations of arsenic also had dose-response relationship (r =0.617,P ＜ 0.01); after 24 h the cells were treated with arsenic,no significant difference of 8-OHdG content in the culture medium was observed(F =2.127,P ＞ 0.05 ).ConclusionNaAsO2 can cause SV-HUC-1 cell oxidative damage.
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Objective To explore the effects of smoking and alcohol drinking on arsenic metabolism of people exposed to different concentrations of arsenic in drinking water.Methods Residents in Shanxi exposed to different concentrations of arsenic in drinking water and age ≥ 18 years old adults were chosen as the subjects for this study in 2008,the subjects were divided into three groups according to the concentrations of arsenic in drinking water: high-arsenic exposure group (more than 0.05 mg/L),low-arsenic exposure group (between 0.01 and 0.05 mg/L) and control group(less than 0.01 mg/L),excluded recently had eaten seafood and had poisoning symptoms of chronic arsenic in drinking water in the crowd.Smoking and alcohol drinking habits were investigated by questionnaire.Arsenic species in the urine samples were detected with hydride generation atomic absorption spectroscopy.Total arsenic(tAs) was the sum of iAs％,MMA％ and DMA％.iAs％,MMA％ and DMA％ were calculated as iAs/tAs,MMA/tAs and DMA/tAs,respectively.The first methylation ratio(FMR) and the secondary methylation ratio(SMR) were calculated as (MMA + DMA)/tAs and DMA/(MMA + DMA),respectively.Results Three hundred and ninety-five adults were chosen in this study.In the high exposure group the alcohol drinking and smoking subjects had higher MMA％(16.24％) but lower SMR(82.19％ ) than the non-drinking and non-smoking subjects (12.16％ and 86.13％,respectively).The differences of both MMA％ and SMR were significant(P ＜ 0.05 ).No significant difference was observed between the non-smoking/non-drinking subjects and the smoking or the drinking subjects(all P ＞ 0.05 ).In the low exposure group there were higher MMA％( 13.86％,13.99％) lower DMA％(72.87％,77.76％)and lower SMR (83.48％,83.90％ ) in those with smoking or drinking/smoking compared with the non-drinking and non-smoking subjects (11.83％,80.35％ and 86.54％,respectively,all P ＜0.05 ).No significant difference was observed between drinkers and non-drinking/non-smoking subjects(P ＞ 0.05).In the control group there were a higher MMA％( 17.27％,17.06％) lower DMA％ (73.89％,72.29％) and lower SMR (81.48％,82.58％ ) in those with smoking or drinking/smoking compared with the non-drinking and nonsmoking subjects( 11.52％,79.68％ and 87.19％,respectively,all P ＜ 0.05).No significant difference was observed between drinkers and the non-drinking/non-smoking subjects (all P ＞ 0.05).ConclusionThe arsenic methylation capacity of people with drinking and smoking is poorer than that of non-drinking and non-smoking subjects after arsenic exposure.
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ObjectiveTo construct geographic information database of drinking water type of endemic arsenism at village level with Google Earth and provide scientific basis for prevention and management of endemic arsenism.MethodsDrinking water samples were collected in the field of Shilegetu village,Tuoketuo county,Inner Mongolia in 2008.Arsenic concentrations were determined by high-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry.Global positioning system(GPS) was performed to obtain the geographic information of the water sources.Google Earth was applied to establish the geographic information database.Results There were 5 drinking water resources in this village.They were located between 40°29′09″ N and 40°29′36″ Nlatitude and 111°28′00″ E and 111°29′02″ E longitude,with the altitude between 1010 m and 1021 m.For all drinking water resources,four water arsenic concentrations was beyond 0.05 mg/L and one below 0.05 mg/L.In addition,one water source had been abandoned and the remaining four were providing daily drinking water for residents of the villages.ConclusionsThe geographic information database,established by Google Earth,can intuitively reflect the real situation of the endemic village.It can provide more useful information for field epidemiological research.It is an effectively tool in control and management of endemic arsenism.
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ObjectiveTo study the protective effects of tert-butylhydroquinone(tBHQ) on sodium arsenite (NaAsO2)-induced cytotoxicity and oxidative injuries. Methods Chang liver cells were pretreated with tBHQ[0(control), 5, 25 μmol/L]for 24 h, and then co-treated with tBHQ(5 μmol/L) together with NaAsO2[0(control),30, 40, 50, 60 μmol/L] for another 24 h, and Alamar blue reduction rates were used to evaluate cell viability,the results were expressed as the relative ratio of Alamar blue reduction rates between the experimental group and the control group. On the other hand, Chang liver cells were pretreated with tBHQ[0(control), 5, 25 μmol/L] for24 h,and then co-treated with tBHQ(5 μmol/L) together with NaAsO2[0(control), 40, 50 μmol/L] for another 24 h,and the levels of cellular reactive oxygen species(ROS) were detected by staining cells with 2',7'-dichlorofluorescin diacetate(DCFH-DA), the results were expressed as the relative ratio of mean fluorescence intensity between the experimental group and the control group. ResultsCell viability decreased dramatically by treatment with NaAsO2(30, 40, 50, 60 μmol/L), while relieved to some extent by pretreatment with 5, 25 μmol/L tBHQ, the main effects of NaAsO2 and tBHQ, as well as their interaction were all statistically significant(F =566.57, 55.09, 14.50,all P ＜ 0.05) ; the cell viability of NaAsO2(30, 40, 50, 60 μmol/L) pretreated with tBHQ(5, 25 mol/L) were 0.75 ±0.02, 0.70 ± 0.04, 0.59 ± 0.03, 0.43 ± 0.03 and 0.75 ± 0.02, 0.73 ± 0.03, 0.65 ± 0.02, 0.50 ± 0.02, respectively,all significantly higher than corresponding NaAsO2 alone groups(0.70 ± 0.03, 0.64 ± 0.03, 0.43 ± 0.03, 0.33 ±0.01, all P ＜ 0.05), the cell viability of NaAsO2(50, 60 μmol/L) pretreated with 25 μmol/L tBHQ was higher than corresponding 5 μmol/L tBHQ pretreatment groups(all P ＜ 0.05). On the other hand, 40, 50 μmol/L of NaAsO2 significantly induced hepatocellular ROS generation, while tBHQ(5, 25 μ mol/L) pretreatment significantly decreased NaAsO2-induced intracellular ROS levels, the main effects of NaAsO2 and tBHQ, as well as their interaction were all statistically significant (F =181.78, 60.55, 4.93, all P ＜ 0.05) ; the ROS levels of NaAsO2(40, 50 μ mol/L) pretreated with tBHQ(5, 25 μmol/L) were 1.87 ± 0.09, 1.80 ± 0.07 and 1.36 ± 0.11, 1.44 ± 0.12,all significantly decreased than corresponding NaAsO2 alone groups(2.30 ± 0.18, 2.18 ± 0.17, all P ＜ 0.05),the ROS levels of NaAsO2(40, 50 μmol/L) pretreated with 25 μmol/L tBHQ decreased than corresponding 5 μmol/L tBHQ pretreatment groups (all P ＜ 0.05). ConclusiontBHQ has a certain antagonism on arsenic induced cytotoxicity and oxidative injuries.
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Objective To investigate the effect of sodium fluoride(NaF) on proliferation, differentiation and the mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor κβ ligand (RAN KL) of mouse osteoblasts. Methods Osteoblasts were isolated from calvarias of Kunming mice born in 1 - 2 d and cultured. Various concentrations of NaF(0, 10-8, 10-7, 10-6, 10-5, 10-4, 10-3mol/L) were added to the culture medium, the proliferation and activity of alkaline phosphatase(ALP) was determined after 72 h or 120 h. The expression of OPG mRNA and RANKL mRNA was analyzed by semi-quantification RT-PCR. Difference among groups was analyzed by One-Way AN0VA. Difference between two groups was analyzed by LSD-t test. Results There was significant difference in cell proliferation among groups after 72 h(F = 13.806, P < 0.05). Compared with control group(0.434 ± 0.010) , the proliferation was significantly induced in 10-7 - 10-4 mol/L groups treated osteoblasts (0.448 ± 0.010, 0.453 ± 0.013, 0.454 ± 0.016, 0.449 ± 0.018, all P< 0.05), and was significantly suppressed in 10-3 mol/L group(0.401 ± 0.009, P < 0.05). There was statistic difference in the activity of ALP among groups(F = 9.021, P < 0.05). Compared with control group (1.677 ± 0.682), the activity of ALP significantly increased in 10-7 - 10-5 mol/L groups[ (2.447 ± 0.756) × 106, (2603 ± 0.183) × 106, (2.687 ± 0.886) × 106 U/L, P < 0.05 or P < 0.01 ] and significantly decreased in 10-4 mol/L group[ (1.479 ± 0.366) × 106 U/L, P < 0.05 ]. There was significant difference in the expression of OPG mRNA among groups(F = 11.299, P< 0.05). Compared with control group (1.000 ± 0.000), the expression of OPG mRNA was significantly increased in 10-7 - 10-4 mol/L groups( 1.058 ± 0.027, 1.053 ± 0.026, 1.088 ± 0.055, 1.069 ± 0.008, P < 0.05 or P < 0.01) , while significantly decreased in 10-3 mol/L group (0.941 ± 0.029, P< 0.05). There was no difference in RANKL mRNA expression among groups (F= 1.311, P> 0.05). The ratio of RANKL/OPG decreased with increasing doses of fluoride and increased in 10-4, 10-3 mol/L groups, but there was no difference between groups(F = 1.376, P> 0.05). Conclusions A biphasic pattern of proliferation and differentiation has been induced in mouse osteoblasts, which manifests stimulation effect in low doses and suppression in higher doses. Low doses of sodium fluoride suppress differentiation and maturation of osteoblasts by increasing expression of OPG mRNA, while high doses of sodium fluoride enhance differentiation and maturation of osteoblasts by decreasing expression of OPG mRNA.
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Objective To observe the metabolism and distribution of arsenic in liver and brain of offspring rata by exposure to arsenic of pregnant rats or lactation dams and weaned pups,and explore if arsenic could penetrate the placental barrier,lactation barrier and blood brain barrier. Methods The Wistar female rots were randomly divided into four groups according to body weights,12 in each group,and were fed with drinking water that contained arsenic(NaAsO_2) 0,10,50,100 mg/L beginning from the gestafional day 6 until pups 42 days old. Pups were separately sacrificed on postnatal day(PND) 0,15,28,42. Arsenic in liver and brain of offspring rots and in breast milk was examined by atomic absorption speetrophotometer with an arsenic speeiation pretreatment system. Results Concentration of iAs,MMA,DMA of brain in 50,100 mg/L groups were higher than that of 0 mg/L group[0,0,0,(7.3±6.6),0,(44.2±27.4)ng/g]on PND 0,42[iAs: (120.0±46.0),(195.5±125.3),(216.5±278.4),(176.6±151.8) ng/g; M MA: (47.2±18.1),(199.6±389.1),(47.4±55.2),(82.7±79.2) ng/g; DMA: (984.3±377.4),(2222.1±1433.2),(998.1±368.3),(1781.3±715.7)ng/g,all P < 0.05]. Concentration of DMA of brain in 50,100 mg/L groups were higher than that of 0 mg/L group[(13.9±18.1),(50.6±98.3)ng/g]on PND 15,28 [(270.3±73.1),(323.9±72.7),(758.7±245.9),(1020.6±383.6) ng/g,all P < 0.05]. Concentration of iAs,DMA of liver in 10,50,100 mg/L groups were higher than that of 0 mg/L group [(1.4±3.5),(49.7± 47.1),0,(100.4±30.2)ng/g]on PND 28,42 [iAs: (37.5±28.1),(268.8±246.4),(307.2±339.9),(15.4±9.4),(479.1±161.1),(408.4±51.9)ng/g;DMA: (594.5±148.8),(3181.9±519.0),(4834.2±2568.4),(1061.8± 85.2),(3697.1±553.7),(4120.0±732.8) ng/g,all P < 0.05]. Concentration of DMA of liver in 10,50,100 mg/L groups were higher than that of 0 mg/L group[(13.2±20.5)ng/g]on PND 15[(182.0±60,2),(637.6±90.0),(1458.7±196.3)ng/g,all P < 0.05]. Concentration of arsenicals of liver and brain showed a dose-dependent increase. The concentrations of DMA of breast milk in 50,100 mg/L groups were also higher than that of 0 mg/L group[(9.8±13.4),0 ng/g]on PND 0,15 [(182.3±85.9),(372.2±203.9),(124.2±33.1),(244.4±196.5)ng/g,all P < 0.05]. In the analysis of the change of arsenic on different postnatal day,we found the concentration of iAs,MMA,DMA,TMA in liver and brain of pups all decreased on postnatal day 15,and was lower than that on PND 0,28 and 42. Conclusions The distribution of arsenic and methyl-metabolism in liver and brain of pups is related with arsenic exposure dose. Arsenic can penetrate the placenta and blood brain barrier easily and lactation can hinder arsenic intake in some extent.
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Objective To observe whether sodium arsenite(NaAsO2)can activate the expressions of hemeoxygenase-1(HO-1)of normal human liver cell line named Chang liver.Methods Chang liver cells were exposed to NaAsO2 at 10 μmoL/L,0(contml),2,6,12,24 h and at 0(control),5,10,25,50 μmol/L in 12 h, followed by the measuring of the expressions of HO-1 protein in ceUs with western blot.Results In 10 μmol/L groups Chang liver cells exposed for 6,12,24 h cultured in vitro,the expressions of HO-l protein(3.97±0.72, 12.92±2.98,23.29±3.82)was significantly higher than that of control(1.00±0.00),and compared with the control, the difference being statistically significant(F=85.83,P＜0.01;t=-9.42,-8.95,-13.83,respectively,P＜ 0.05 or＜0.01).In 12 h,5,10,25 and 50 μmol/L groups cultured in vitro,the expressions of HO-1(16.34±0.25, 7.75±0.39,7.93±0.14,12.48±0.35)was significantly higher than that of control(1.00±0.00).and compared with the control,the difference being statistically significant(F=85.83,P＜0.01;t=-36.25,-30.19,-86.40, -56.40,respectively,all P＜0.01).Conclusion Inorganic arsenic call induce the activation of HO-1,promote the expression of protein in a time-and dose-dependent manner.
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Objective To explore the distribution of arsenic speciafion and to estimate the effect of arsenic on glutathione(GSH)levels in the blood and liver of mice exposed to different concentrations of inorganic AsⅢ through drinking water.Methods Mice drank water containing arsenite at concentrations of iAsⅢ of 0(contr01),25,50,100 ms/L for 6 weeks.Blood and liver were sampled to asses$the levels of inorganic arsenic(iAs),monomethylarsenic acid(MMA),dimethylarsenic acid(DMA)by the method of hydride generation trapping and ultra-hypothermia coupled with atomic absorption spectrometry,and the level of GSH by the method of 5,5'-Dithio-bis (2-Nitrobenzoic acid).Results Leveh of iAs.MMA and DMA in blood and in liver increased along with the increase of iAs concentrations in drinking water.Primary methylated index(PMI)and secondary methylation index (SMI)of liver and blood were significantly higher in exposed groups than those in control group(P＜0.05).SMI of liver in 50 mg/L exposed group[(50.45±2.94)%]was significantly higher than those in 25 mg/L and 100 mg/Lgroups[(41.68±7.09)%and(41.19±8.87)%,respectively],the difference being statistically significant(P＜0.05).The ratio of iAs.MMA and DMA in blood and liver in exposed group were 2:3:5 and 4:3:3,the percentage of level of organic arsenic(MMA+DMA)were 80%and 60%.GSH in blood and liver in exposed group decreased along with iAs concentrations in drinking water and had significant differences compared with those in control group (P＜0.05).However,levels of GSH in liver and blood did not differ significantly between exposed groups and control group(P＞0.05).Conclusions Membolism of iAs in liver is maximized when the iAs concentrations in drinking water increases to a certain level.However,the percentage of arsenic speciation in blood is different from that in liver,suggesting that other organs and tissues may be capable of methylation of inorganic arsenic.The level of GSH in liver and blood in mice is a good mark tO reflect the toxicity of arsenic.
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Objective To evaluate effects of chronic arsenic exposure and arsenic exposure time on oxidative DNA lesions in humans. Methods A cross-sectional study was conducted in 108 subjects exposed to high concentrations of arsenic in drinking water and 75 control subjects. A cohort study was conducted in 64 subjects exposed to high levels of arsenic in drinking water for 7 or 9 years. Urinary 8-oxo-7,8-dihydredeoxygnanine(8-OHdG) levels were analyzed by the enzyme-linked immunosorbent assay kit(ELISA). Urinary arsenic concentration was detected with hydride generation atomic absorption spectroscopy. Results In the cross-sectional study, the median of urinary arsenic concentration was 484.17 mg/kg Cr for the arsenic-exposed group, and 13.80 mg/kg Cr for the control group, and the difference between the two groups was statistically significant (t=32.57, P<0.01). The median of urinary 8-OHdG levels was 16.60 and 21.88 mg/kg Cr for arsenic-exposed children and adults respectively, much higher than control children(10.50 mg/kg Cr) and adults (9.11 mg/kg Cr), and the difference was statistically significant (t=5.049, 6913, all P<0.01). Urinary 8-OHdG levels were signifieandy lower for children than adults in the exposed group(t=-1.997, P<0.05). In the cohort study, the median of urinary arsenic concentration was 461.3 mg/kg Cr for the 7-year-exposed subjects and 422.90 mg/kg Cr for the 9-year-expesed subjects, and no significant difference was observed(t=-0.250, P 0.05). The median of urinary 8- OHdG levels for 9-year-exposed children and adults were 23.46 and 24.30 mg/kg Cr respectively, significantly increased compared with those of 7-year-exposed(14.29 and 18.38 mg/kg Cr), and the difference had statical signhqcanees (t= -2.949,-3.055, all P<0.01). Conclusions Chronic arsenic exposure can lead to oxidative DNA lesions in humans. The arsenic-induced DNA lesions may aggravate with the exposure time in a certain period.
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<p><b>OBJECTIVE</b>To explore the effect of glutathione (GSH) and sodium selenite on the metabolism of arsenic in the liver, kidney and blood of mice exposed to iAsIII through drinking water.</p><p><b>METHODS</b>The mice were randomly divided into control, arsenic, GSH and sodium selenite group, respectively. And each group had eight mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks. Mice were intraperitoneally injected with GSH (600 mg/kg) and sodium selenite (1 mg/kg) for seven days from the beginning of the fourth week. At the end of the fourth week, liver, kidney and blood were sampled to assess the concentrations of inorganic arsenic (iAs), monomethylarsenic acid (MMA), dimethylarsenic acid (DMA) by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry.</p><p><b>RESULTS</b>The liver DMA (233.76 +/- 60.63 ng/g) concentration in GSH group was significantly higher than the arsenic group (218.36 +/- 42.71 ng/g). The concentration of DMA (88.52 +/- 30.86 ng/g) and total arsenic (TAs) (162.32 +/- 49.45 ng/g) in blood of GSH group was significantly higher than those [(45.32 +/- 12.19 ng/g), (108.51 +/- 18.00 ng/g), respectively] of arsenic groups(q values were 3.06, 6.40, 10.72 respectively, P < 0.05). The primary methylated index (PMI) (0.65 +/- 0.050) and secondary methylated index (SMI) (0.55 +/- 0.050) in liver sample of GSH group were significantly higher than those (0.58 +/- 0.056, 0.44 +/- 0. 093) in arsenic group. In blood samples, the PMI (0.85 +/- 0.066) in GSH group was significantly higher than that (0.54 +/- 0.113) in arsenic group (q values were 3.75, 5.26, 4.21 respectively, P < 0.05). However, no significant difference was identified between sodium selenite and arsenic groups in liver, kidney or blood samples. And no significant difference was detected in kidney samples among all arsenic exposing groups.</p><p><b>CONCLUSION</b>Exogenous GSH could promote the methylated metabolism of iAsIII, but sodium selenite showed no significant effects.</p>
Subject(s)
Animals , Female , Male , Mice , Arsenic , Metabolism , Arsenic Poisoning , Metabolism , Environmental Exposure , Glutathione , Pharmacology , Mice, Inbred Strains , Sodium Selenite , Pharmacology , Water SupplyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of sodium arsenite on the activity, the mRNA and the protein expression of CAT in human keratinocyte cell line (HaCaT).</p><p><b>METHODS</b>The activity of catalase (CAT) was detected by ultraviolet direct velocity assay. RT-PCR was used to detect the mRNA expression of CAT and Western blotting was conducted to detect the protein expression of CAT.</p><p><b>RESULTS</b>If the cells were treated with higher than 5.0 micromol/L sodium arsenite, the activity, mRNA and protein expression of CAT were decreased significantly and in a dosage dependent fashion (P < 0.05).</p><p><b>CONCLUSION</b>CAT is inhibited by sodium arsenite in the transcription, translation and activity levels.</p>
Subject(s)
Humans , Arsenites , Toxicity , Blotting, Western , Catalase , Genetics , Cell Line , Dose-Response Relationship, Drug , Keratinocytes , RNA, Messenger , Genetics , Reverse Transcriptase Polymerase Chain Reaction , Sodium Compounds , ToxicityABSTRACT
<p><b>OBJECTIVE</b>To study the effects of fluoride on the proliferation and differentiation of osteoblasts in sucking rats and the antagonism of vitamin Cin vitro.</p><p><b>METHODS</b>The enzyme digesting method was used to isolate the rat osteoblasts; the proliferative response was determined by the percents of reduced alamarBlue; the activity of alkaline phosphatase (ALP) was measured by ELISA method.</p><p><b>RESULTS</b>The proliferation of sucking rat osteoblasts was increased at 0.10 - 1.00 mmol/L of NaF, whereas inhibited at >or= 2.00 mmol/L. ALP activity was increased at 0.01 - 0.05 mmol/L of NaF, and decreased at >or= 0.10 mmol/L. The inhibition on proliferation and differentiation at 2 mmol/L NaF was antagonized by vitamin C.</p><p><b>CONCLUSION</b>Fluoride had a two-phase effect on osteoblasts, vitamin C could antagonize the inhibitory effect of higher concentration of fluoride on proliferation and differentiation of osteoblasts.</p>