Effects of pyrrolidine dithiocarbamate on expressions of α-smooth muscle actin, integrin α5 and fibronectin in acute paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the expressions of α-SMA, integrin α5 and fibronectin (Fn) in acute paraquat poisoned rats and the effect of PDTC. To investigate the mechanism of paraquat-induced pulmonary fibrosis.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into three experimental groups: Control group (6 rats), PQ group (36 rats) and PQ+PDTC group (36 rats). On the 1st, 3rd, the 7th, the 14th, the 28th and the 56th day after exposure, the protein expression of α smooth muscle actin (α-SMA) was evaluated by western blot. The mRNA levels of integrin α5 and fibronectin (Fn) were analyzed with real-time quantitative PCR (RT-PCR). Meanwhile, the lung pathological changes were observed and semi-quantified.</p><p><b>RESULTS</b>T With the time passing, the expression of α-SMA in PQ group increased gradually compared with control group (P < 0.05 or P < 0.01). The increasing extent was gently on the 3 rd, the 7 th day. While increasing extent was rapidly from the 28 th to the 56 th day. RT-PCR showed PQ significantly increased Fn mRNA level on all time points and increased integrin α5 mRNA level from the 7 rd to 56 th day compared with control group (P < 0.05 or P < 0.01). PDTC treatment significantly deceased α-SMA, Fn, and integrin α5 levels compared with PQ group in corresponding time points (P < 0.05 or P < 0.01) Noteworthy, in PQ+PDTC group, the occurrence of pathological changes were drastically attenuated and pathologic score significantly decreased (P < 0.05 or P < 0.01).</p><p><b>CONCLUSIONS</b>α-SMA, integrin α5 and fibronectin could play an important role in the development of pulmonary fibrosis caused by paraquat poisoning. PDTC, asa strong NF-κB inhibitor, may inhibit NF-κB activity and further significantly decreased expressions of α-SMA, integrin α5 and fibronectin which were important part of ECM, leading to drastically attenuated pulmonary fibrosis. However, the mechanisms of PDTC intervention still remains to be explored.</p>

Determination of1-bromopropane in the workplace air by GC-FID / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish a method for determination 1-bromopropane (1-BP) in workplace air by gas chromatography-flame ionization detector (GC-FID).</p><p><b>METHOD</b>1-bromopropane in workplace air was collected with activated charcoal tube, then desorbed by carbon disulfide and determined by GC-FID. 1-bromopropane was quantitatively measured using retention time and peak area.</p><p><b>RESULTS</b>Linear regression formula was Y = 3353.4x-10064 in a range of 2.50 ∼ 500.00 µg/ml with regression coefficient R = 0.9998. Detection limit was 0.25 µg/ml and the lowest detection concentration of 1-brmopropane in air was 0.14 mg/m(3) (at air volume 1.8L). The mean recoveries of 1-BP were between 96.8% and 102.6%, and relative standard deviation of inter and intra-assay was less than 10%. The average desorption efficiencies were between 93.2% and 104.4%. The samples in activated charcoal tube could be stably stored for 5 days at room temperature.</p><p><b>CONCLUSION</b>The method could be feasible to determine 1-bromopropane in workplace air.</p>

Paraquat involves differentiation of human neural stem cells via Notch signaling / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate effects of paraquat on the mRNA expression of key elements of Notch signaling (Notch1, Jagged1 and DTX1) during differentiation process of human neural stem cells (hNSCs).</p><p><b>METHODS</b>hNSCs exposed to PQ at the concentrations 0.10, 1.00, 10.00 M. Cell proliferation ability was assessed using MTT assay and mRNA expressions of Notch1, Jagged1 and DTX1 were detected by Real-time RT-PCR at 2, 4, 8, 12 d of differentiation.</p><p><b>RESULTS</b>Compared with control group, NOTCH1, JAG1 mRNA expression levels exposed to PQ at the concentration of 0.10 M significantly reduced at 2, 4, 8 d and significantly went up at 12d (P < 0.01). Compared with control group, NOTCH1, JAG1 and DTX1 mRNA expression levels exposed to PQ at the concentration of 10.00 M significantly reduced at 2, 8, 12 d (P < 0.01). PQ could down-regulate Notch1, Jagged1 and DTX1 mRNA expressions at the early stage of differentiation, then up-regulate Notch1 mRNA expression, and down-regulate Notch1, Jagged1 and DTX1 mRNA expressions at the end of differentiation.</p><p><b>CONCLUSION</b>Notch signaling pathway may be involved in differentiation of neural stem cell exposed to PQ.</p>

Intervention of pyrrolidine dithiocarbamate on expressions of connective tissue growth factor, type I collagen, and type III collage in acute paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the changes in the expression of connective tissue growth factor (CTGF), type I collagen (Col I), and type III collagen (Col III) among the rats with acute paraquat (PQ) poisoning and the intervention effect of pyrrolidine dithiocarbamate (PDTC) on their expression, and to investigate the mechanism of PQ-induced pulmonary fibrosis and the intervention effect of PDTC on the disease.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into control group (n = 6), PQ group (n = 36), and PQ + PDTC group (n = 36). The PQ group and PQ + PDTC group were given a single dose of saline-diluted PQ (80 mg/kg) by gavage; 2 h later, the PQ + PDTC group was intraperitoneally injected with a single dose of PDTC (100 mg/kg), and the PQ group was intraperitoneally injected with the same amount of saline. The control group was given saline (1 ml/kg) by gavage and was intraperitoneally injected with the same amount of saline 2h later. At 1, 3, 7, 14, 25, and 56 days after operation, the protein expression of CTGF was evaluated by Western blot; the mRNA expression of CTGF, Col I, and Col III was analyzed by real-time quantitative PCR; the content of hydroxyproline in lung tissue was measured, and the pathological changes of lung tissue of the poisoned rats were observed.</p><p><b>RESULTS</b>The protein expression of CTGF in the PQ group increased as the time went on, slowly from the 3rd to the 14th day and rapidly from the 28th to the 56th day, significantly higher than that in the control group at each time point (P < 0.05 or P < 0.01). The mRNA expression of CTGF in the PQ group began to rise markedly on the 1st day, increased rapidly from the 3rd to the 14th day, and remained at a relatively high level from the 28th to the 56th day, significantly higher than that in the control group at each time point (P < 0.01). The mRNA expression of Col I in the PQ group changed little on the 1st and 3rd day, increased slightly on the 7th day, and increased greatly from the 14th to the 56th day, significantly higher than that in the control group from the 7th to the 56th day (P < 0.05 or P < 0.01). The mRNA expression of Col III in the PQ group began to rise on the 1st day, reached the peak level on the 7th day, and then declined, significantly higher than that in the control group at each time point (P < 0.05 or P < 0.01). Masson staining showed that fibroblasts proliferated from the 14th to the 28th day, and collagen fibers increased gradually. Compared with the PQ group, the PQ + PDTC group showed significantly decreased protein expression of CTGF as well as mRNA expression of CTGF, Col I, and Col III (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>In PQ-induced pulmonary fibrosis, the expression of CTGF keeps rising, and the collagen secretion and matrix synthesis are increased probably by upregulating the transcriptional levels of Col I and Col III; CTGF plays an important role in PQ-induced pulmonary fibrosis. PDTC can inhibit the expression of CTGF, thus reducing the lung injury in rats with PQ poisoning.</p>

Involvement of excitatory amino acid system in astrocytes activation caused by dimethoate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the involvement of excitatory amino acid system in astrocytes activation caused by dimethoate.</p><p><b>METHODS</b>Pure-cultured astrocytes were gained by three passages from primary cultured rat nerve cells, then treated with 10(-6),10(-5),10(-4) mol/L dimethoate for 48 h, 50 micromol/L and 100 micromol/L MK801, a NMDA receptor blocker, was used to intervene the effects induced by 10(-4) mol/L dimethoate. HPLC-FLD was utilized to measure the concentrations of excitatory amino acid (EAA), RT-PCR was used to detect the expression levels of NR2B, GLT-1, GLAST, GFAP and S100beta mRNA, and immunofluorescence staining method was applied to measure the expression levels of GFAP and S100beta proteins.</p><p><b>RESULTS</b>The expression levels of GLAST mRNA in all exposure groups were 67.8%, 68.6% and 76.2% of control level, respectively, which were significantly lower than that of control group (P < 0.05); The concentrations of EAA significantly decreased in 10(-4) mol/L dimethoate group, as compared with control group (P < 0.01); the expression levels of GFAP mRNA in 10(-4) mol/L dimethoate group, of S100beta mRNA in 10(-5) mol/L dimethoate group, of GFAP protein in 10(-4) mol/L and 10(-5) mol/L dimethoate groups and S100beta protein in 10(-4) mol/L dimethoate group were significantly higher than those in control group (P < 0.01). The expression levels of GLT-1 and GLAST mRNA in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups increased significantly, as compared with 10(-4) mol/L dimethoate group (P < 0.01), the expression levels of NR2B mRNA in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups increased significantly, as compared with control group (P < 0.05 or P < 0.01); the concentration of Glu in 10(-4) mol/L dimethoate plus 100 micromol/L MK801 group increased significantly, as compared with 10(-4) mol/L dimethoate group (P < 0.01); the expression levels of GFAP mRNA and protein in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups decreased significantly (P < 0.01); S100beta protein expression level in 50 micromol/L MK801 intervention group was significantly higher than thatl in control group (P < 0.01).</p><p><b>CONCLUSION</b>Excitatory amino acid system involved in astrocytes activation caused by dimethoate. MK801 was useful to control astrocytes gliosis.</p>

Role of connective tissue growth factor and α-smooth muscle actin in pulmonary fibrosis among acute paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>to observe the expression of the connective tissue growth (CTGF) and a smooth muscle actin (α-SMA) in acute paraquat (PQ) poisoned rats and investigate the mechanism of paraquat-induced pulmonary fibrosis.</p><p><b>METHODS</b>sprague-Dawley rats were randomly divided into two experimental groups: control group (6 rats) and PQ group (56 rats). On the 3rd, the 7th, the 14th, the 28th and the 56th day after exposure, the expression of CTGF and α-SMA were evaluated by SABC Immunohistochemistry and Western blot; and the relationship of the expression with pathologic score, hydroxyproline were also analyzed, respectively. The lung pathological changes of rats were observed and pathological evaluation was made.</p><p><b>RESULTS</b>it was similar that the expression pattern of CTGF, α-SMA detected by immunohistochemistry and Western blot. With the time passing, their expression in PQ group increased gradually compared with control group (P < 0.05 or P < 0.01). The increasing extent of CTGF, α-SMA were gentle on the 3rd, the 7th day. While their increasing extent was rapid from the 14th to the 56th day. CTGF was positively correlated with α-SMA, pathologic score and hydroxyproline respectively (r = 0.74, r = 0.87, r = 0.71, P < 0.05 or P < 0.01). Meanwhile, the histological changes such as lung fibroblast proliferation, disorganized collagen fibers were observed in PQ group.</p><p><b>CONCLUSION</b>CTGF and α-SMA could play an important role in the development of pulmonary fibrosis caused by paraquat poisoning; CTGF may promote the transformation of fibroblasts to myofibroblasts and further strengthen the ability of synthesis collagen and extracellular matrix.</p>

Effects of controlling specific dangerous pesticides on prevention of acute pesticide poisoning in rural area / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of controlling the specific dangerous pesticides on prevention of acute pesticide poisoning in rural area.</p><p><b>METHODS</b>The data of reported cases of pesticide poisoning were analyzed to find out the specific dangerous pesticide in acute pesticide poisoning. Then the occurrence of occupational pesticide poisoning and fatality of non-occupational pesticide poisoning were estimated under the hypothesis of removing the specific dangerous pesticides.</p><p><b>RESULTS</b>The data indicated that parathion (including methyl parathion) was the specific dangerous pesticide inducing occupational pesticide poisoning. After removing the use of parathion, the hazard of pesticides which caused occupational pesticide poisoning would be significantly decreased (P < 0.01). Parathion was also the most dangerous pesticide which caused non-occupational pesticide poisoning, with its fatality up to 15.8%. If parathion was well controlled, the fatality of non-occupational pesticide poisoning would be declined from 9.4% to 7.4%. The analyses of related literatures also revealed the similar results.</p><p><b>CONCLUSION</b>The occurrence of occupational pesticide poisoning and fatality of non-occupational pesticide poisoning may decrease if the most dangerous pesticides are well supervised.</p>

Toxic effect of neonatal exposure to 2,2',4,4',5,5'-hexa-chlorobiphenyl on spermatogenesis in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To determine the long-term testicular effect after neonatal exposure to 2,2', 4,4',5,5'-hexa-chlorobiphenyl (PCB153).</p><p><b>METHODS</b>On birth day (Postnatal day 0, PNDO), the Sprague-Dawley (SD) male rats were mixed together and divided into 12 pups/litter. At PND1, the rats were grouped randomly into control and treatment groups according to different litters, 24 pups/group. They were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, 0.250 and 2.500 mg/kg BW-day from PNDI to PND7. The rats were sacrificed at PND8 and PND90 by anesthesia. The testes were collected and weighed for histological examination and daily sperm production at PND8 or/and PND90. The epididymidis and the epididymidis cauda also were collected and weighed for determination the sperm counts at PND90.</p><p><b>RESULTS</b>The body weight of 2.500 mg/kg dose group was decreased significantly from PND3 to PND8 compared with that of control (P < 0.05). At PND8, the loose structure in seminiferous cord and the spermatogonia with enlarged volume and detached from the cord were observed in 2.500 mg/kg dose group by light microscope and electronic microscopy. With the increase of exposure doses, the testicular daily sperm production (DSP) and the sperm counts of epididymidis cauda were decreased in dose-dependent manner at PND90. The DSP in 0.250 mg/kg [30 x 10(6)/testis(g)] and 2.500 mg/kg [18 x l0(6)/testis(g)] dose groups were significantly reduced compared with that of control [36 x 10(6)/testis(g)] (P < 0.05). And there was a significant reduction in the sperm counts of epididymidis cauda in 0.250 mg/kg [42 x 10(7)/epididymidis cauda (g)] and 2.500 mg/kg [18 x 10(7)/epididymidis cauda (g)] dose groups compared with that of control [51 x 10(7)/epididymidis cauda (g)] (P < 0.05).</p><p><b>CONCLUSIONS</b>The spermatogenesis of adult testis is disturbed, which causes the decrease in the testicular DSP and the sperm counts of epididymidis cauda after neonatal exposure to PCB153. The long-term damage in male reproductive function is caused by neonatal exposure to chemicals.</p>

Risk assessment of nerve conduction velocity in workers exposed to lead / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the dose-effect relationship between lead exposure and nerve conduction velocity, and to assess risk characteristics of nerve conduction velocity induced by lead exposure.</p><p><b>METHODS</b>The external dose, internal dose (blood lead, urine lead) and the conduction velocity of peripheral nerve were examined. The benchmark dose of a population exposed to occupational lead was estimated to develop risk assessment of nerve conduction velocity in worker exposed to lead by use of BMDS (version 1.3.3). The BMDL in terms of blood lead and urine lead was calculated.</p><p><b>RESULTS</b>There was correlation between blood lead and urine lead. The sense nerve conduction velocity was decreased significantly in the group of lead exposure workers (P < 0.05). The BMDLs-05 for median nerve conduct velocity, ulnar nerve conduction velocity, and superficial peroneal nerve conduction velocity in terms of blood lead were 456.99, 332.36 and 468.38 microg/L respectively; the BMDLs-05 in terms of urine lead were 14.1, 9.2 and 13.6 microg/gCr respectively.</p><p><b>CONCLUSION</b>The internal dose is the better index to reflect the level of lead exposure. Blood lead is identified as a specific and sensitive biomarker for sense nerve conduction velocity reduction. Ulnar nerve conduction velocity can be used as highly sensitive biomarkers to screen the high risk population of lead exposure.</p>

Risk assessment of renal dysfunction caused by occupational lead exposure / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To assess the risk of renal dysfunction caused by occupational lead exposure through epidemiological investigation.</p><p><b>METHODS</b>The workers in a battery factory were selected as the subjects for the exposure and effect assessment. The occupational environmental monitoring data was collected and used to calculate the total external dose of lead. The relationship between external dose and internal dose of lead was analyzed. The external dose, blood lead (BPb) and urinary lead (UPb) were used as exposure biomarkers while the urinary N-acetyl-D-glucosaminidase (UNAG), and urinary albumin (UALB) were used as the effect biomarkers for the renal dysfunction caused by lead. Software of BMDS (BMDS 11311) was used to calculate BMD.</p><p><b>RESULTS</b>The external and internal does of lead was positively correlated (BPb: r = 0.466, P < 0.01; UPb: r = 0.383, P < 0.01). The levels of BPb, UPb in exposure group (654.03 microg/L, 143.45 microg/g Cr) were significantly higher than those in the control group (57.12 microg/L, 7.20 microg/g Cr), so were UALB, UNAG; in addition, all of them presented significant dose-response relationship. The BPb BMD of UALB, UNAG were 607.76, 362.56 microg/L respectively and the UPb BMD of UALB, UNAG were 117.79, 78.79 microg/gCr respectively.</p><p><b>CONCLUSION</b>Occupational lead exposure can cause renal dysfunction, which presents dose-response relationship; the risk assessment of renal dysfunction caused by occupational lead exposure is performed by BMD calculation of BPb and UPb.</p>

Change of oxidative stress and nuclear factor-kappa B in acute paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the change of oxidative stress and nuclear factor-kappaB (NF-kappaB) activity in acute paraquat (PQ) poisoned rats and the effect of PDTC.</p><p><b>METHODS</b>144 SD rats were randomly divided into four experimental groups: control group (6 rats), PDTC group (36 rats), PQ group (56 rats) and PQ + PDTC group (46 rats). On the 1st, the 3rd, the 7th, the 14th, the 28th and the 56th day after treatment, the level of malondialdehyde (MDA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) in serum were detected; the content of hydroxyproline (Hyp) and the activity of NF-kappaB in lung tissues were detected; the lung pathological changes of rats were observed.</p><p><b>RESULTS</b>The level of MDA and MPO in serum increased and the activity of GSH-Px, SOD, CAT in serum decreased significantly in PQ group compared with control and PDTC group (P<0.05 or P<0.01) in the corresponding sacrifice dates. There were a significant decrease of MDA and increase of GPx, SOD, CAT in PQ + PDTC group compared with PQ group (P<0.05 or P<0.01) in the corresponding sacrifice dates. The activity of NF-kappaB in lung tissue of PQ group significantly increased on the 1st, the 3rd, the 7th and 14th day compared with control and PDTC group (P<0.01). There was a significant decrease in NF-kappaB activity on the 1st, the 3 rd, the 7th day in PQ + PDTC group compared with PQ group (P<0.05 or P<0.01). The MPO activity on the 14th day was (119.56 +/- 21.23) U/L, was lower than that of PQ group (P<0.05). Meanwhile, the content of Hyp in PQ group was significantly higher than control and PDTC group on the 14th, the 28th and the 56th day (P<0.01), and its content was lower in PQ + PDTC group on the 28th and the 56th day (0.89 +/- 0.05), (0.93 +/- 0.13) microg/mg compared with PQ group (P<0.01). The histological changes such as alveolitis and fibrosis in PQ + PDTC group were slighter than those in PQ group.</p><p><b>CONCLUSION</b>Oxidative stress and NF-kappaB could play an important role in lung injury of poisoned rats. PDTC may improve redox imbalance and inhibit the expression of NF-kappaB and therefore might have therapeutic effect on acute paraquat poisoning.</p>

Changes of cytokine and nuclear factor-kappa B in acute paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the changes of cytokine and NF-kappaB activity in acute paraquat poisoned rats and the effect of PDTC and the mechanism of lung injury caused by paraquat poisoning.</p><p><b>METHODS</b>Sprague-Dawley (SD) rats were randomly divided into three groups: Control group (6 rats), PQ group (56 rats) and PQ + PDTC group (46 rats). On the 1st, the 3rd, the 7th, the 14th, the 28th and the 56th day after treatment, the level of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta1) and platelet-derived growth factor (PDGF) in serum were detected; the activity of NF-kappaB in lung tissues was detected.</p><p><b>RESULTS</b>The level of IL-1 beta increased significantly on the 1st, the 3rd, the 7th day in PQ group compared with control group (P<0.01). The content of TGF-beta1 and TNF-alpha in PQ group significantly increased compared with control group (P<0.05 or P<0.01). The level of PDGF significantly increased on the 7th, the 14th, the 28th and the 56th day compared with control group (P<0.01). Meanwhile, IL-1 beta and TNF-alpha were positively correlated with lung coefficient (r=0.37, 0.46, P<0.05 or P<0.01 ); TGF-beta1 and PDGF had positive correlation with hydroxyproline (r=0.56, 0.89, P<0.01). The activity of NF-kappaB in lung tissue of PQ group significantly increased on the 1st, the 3rd, the 7th and 14th day compared with control (P<0.05 or P<0.01). There was a significant decrease of IL-1 beta, TGF-beta1, TNF-alpha and PDGF in PQ + PDTC group compared with PQ group (P<0.05 or P<0.01) in the corresponding sacrifice dates. There was a significant decrease in NF-kappaB activity on the 1st, the 3rd, the 7th day in PQ + PDTC group compared with PQ group (P<0.01).</p><p><b>CONCLUSION</b>The cytokine and NF-kappaB could play an important role in lung injury of poisoned rats. PDTC may inhibit the expression of NF-kappaB and further reduce the production of cytokines, alleviate lung injury in acute paraquat poisoned rats.</p>

Effect of neonatal exposure to environmental pollutants on the DNA methylation of rat testis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of neonatal exposure of DNA methylation inhibitor, Cadmium and PCB153 on DNA methylation, apoptosis and spermatogenesis in SD rats.</p><p><b>METHODS</b>Neonatal SD rats were randomly divided into 10 groups and received oral administrations of PCB153 (0.025, 0. 250, 2.500 mg/kg), or Cadmium (1, 2, 4 mg/kg), or positive control 5-Aza-CdR (0.025, 0.250 mg/kg), or vehicle control for five days from PND3. Half of the rats were killed 24 h after the last administration. The remains were fed until 12 weeks. Sperm numbers, apoptosis and DNA methylation levels in testis were investigated.</p><p><b>RESULTS</b>The daily sperm production was significantly decreased in each neonatal exposed group (P < 0.05). Neonatal rats exposed to 5-Aza-CdR and Cadmium reduced the global DNA methylation level, increased apoptosis, while PCB153 exposure did not significantly change DNA methylation and apoptosis.</p><p><b>CONCLUSION</b>Neonatal rats exposed to chemicals could reduce spermatogenesis via multiple pathways. Lower DNA methylation and increased neonatal apoptosis were suggested as one of the causes.</p>

Effect of dimethoate on primary cultured rat cortical neuron / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanisms of dimethoate on the primary cultured cortical neuronal cell injury.</p><p><b>METHODS</b>Cortical neuronal cells were isolated and cultured in serum free medium for 6 days in vitro, and 1, 5, 10, 50 and 100 micromol/L dimethoate were added to the medium and intracellular SOD, MDA and GSH. The content of excitatory amino acid was measured after 48 hours. Flow cytometry was used to detect the neuronal cell apoptosis.</p><p><b>RESULTS</b>After 48 h, the activity of SOD and the content of GSH decreased [(1.04 +/- 0.02), (0.99 +/- 0.02), (0.96 +/- 0.02), (0.91 +/- 0.02) U/mg pro] [(219.35 +/- 6.79), (205.6 +/- 6.29), (194.06 +/- 2.63), (93.68 +/- 7.56) mg/g pro], and the content of MDA increased obviously with 5, 10, 50 and 100 micromol/L dimethoate [(21.22 +/- 0.29), (24.01 +/- 0.34), (27.15 +/- 1.02), (32.91 +/- 1.39) nmol/mg pro]; The content of Asp from 10 to 100 micromol/L dose group was higher than the control group and the content of Glu from 1 to 100 micromol/L dose group was higher than the control group. The apoptosis rate had great significance between 1 to 100 micromol/L dose groups and control group. When treated with dimethoate, MDA content in neuron was positively correlated with the content of EAAs with the increase of dimethoate. The correlative coefficient was 0.937 and 0.759 respectively (P < 0.01), while it was negatively correlated with the content of GSH. The correlative coefficient was -0.868 and -0.801 respectively (P < 0.01).</p><p><b>CONCLUSION</b>The oxidative damage and changes of excitatory amino acid content induced by Dimethoate contribute to the primary cultured rat cortical neuron apoptosis.</p>

Influence of pyrrolidine dithiocarbamate (PDTC) on expression of transforming growth factor beta(1), matrix metalloproteinase-2 and tissue inhibitor-1 of metalloproteinase in rats with pulmonary damage induced by paraquat / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expression of transforming growth factor beta(1) (TGF-beta(1)), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ).</p><p><b>METHODS</b>Fifty-four healthy male SD rats were randomly assigned into the control group (normal saline), the PQ-treatment groups (4 groups) and the PDTC treatment groups (4 groups). Except the rats in the control group, the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC (i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-beta(1) protein in the plasma, the mRNA expression of TGF-beta(1), MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope.</p><p><b>RESULTS</b>The TGF-beta(1) protein, TGF-beta(1) and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P < 0.05 or P < 0.01), while the mRNA level of TIMP-1 was augmented continuously (P < 0.01) throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group, the TGF-beta(1) mRNA expression on the 3rd and the 14th day, 0.54 +/- 0.08 and 0.72 +/- 0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62 +/- 0.50 and 1.97 +/- 0.34 respective-ly, and the TIMP-1 mRNA on the 7th and 21st day, 1.79 +/- 0.21 and 2.00 +/- 0.34 respectively, were significantly decreased (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>PDTC could attenuate paraquat-induced up-regulation of TGF-beta(1) and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjust-ing the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.</p>

Protective effects of vigabatrin and atropine against dimethoate induced-intoxication in mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of vigabatrin and atropine against the acute toxicity of dimethoate in male Kun-min mice.</p><p><b>METHODS</b>The therapeutic schedules of vigabatrin (50 or 100 mg/kg) and (or) atropine (2.5 or 5.0 mg/kg) were performed according to the L(9) (3(4)) orthogonal test table. The survival time, the righting reflex and the onset of muscle fasciculations were observed after the administration of dimethoate.</p><p><b>RESULTS</b>First, the main effects of vigabatrin, atropine and the interaction between them were statistically significant in the Univariate analysis of the survival time at the alpha level of 0.05 (F(V)= 4.73, P(V)= 0.015, F(A)= 50.88, P(A)= 0.000, F(VxA)= 4.17, P(VxA)= 0.007). The range of atropine was more than double of that of vigabatrin or their interaction (R(A)> 2RV or 2R(VxA)). So not only atropine and vigabatrin but also their combination interaction protected mice against dimethoate lethality. The atropine played the major role in diminishing the lethality induced by dimethoate. Second, only vigabatrin, while not atropine, delayed the mice from dimethoate-induced muscle fasciculation according its statistical results (F(V)= 6.87, P(V)= 0.003, F(A)= 0.03, P(A)= 0.968, F(VxA)= 1.134, P(VxA)= 0.356). It should be noted that vigabatrin could not completely prevent dimethoate induced-muscle fasciculation in the test. At last, both atropine and vigabatrin could maintain the righting reflex in the intoxication, however there was no interaction between them (F(V)= 5.81, P(V)= 0.006, F(A)= 9.05, P(A)= 0.001, F(VxA)= 1.34, P(VxA)= 0.257).</p><p><b>CONCLUSION</b>Combined treatment with atropine and vigabatrin in the organophosphates intoxication seems reasonable and acceptable.</p>

Effects of 90-day oral dimethoate exposure on glutamatergic system and neurobehavioral performance in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the spatial learning and exploration along with the CNS excitatory amino acid neurotransmitters profiles in adult rats subchronically exposed to the anticholinesterase organophosphorus insecticide dimethoate.</p><p><b>METHODS</b>Rats were gavaged daily with dimethoate (0, 5, 10 or 20 mg/kg via oral) in NS. for 90 days. Morris water maze tasks were used to test the spatial learning and memory in the rats after the dimethoate exposure. Simultaneously, rats were decapitated for the determination of brain cholinesterase AChE activities, glutamate concentrations, and the NMDA receptor NMDA-R densities and affinities in hippocampus.</p><p><b>RESULTS</b>Latencies to find a hidden escape platform were significantly longer in dimethoate dosed groups than that of the control group in the place navigation tests. Subsequently, the times of crossing the location of platform which had been removed obviously decreased in the highest dose group compared with that of the control in the spatial probe tests (P < 0.05). AChE activity was significantly reduced 42% approximately 78% by all three doses of dimethoate (P < 0.05). Glutamate concentrations were increased significantly 132.9% approximately 134.5% by the two highest doses of dimethoate (P < 0.05). In addition, the NMDA receptor bindings were reduced 21.2% approximately 23.2% with the statistical significance at the same two highest doses (P < 0.05). Furthermore, the receptor affinities was reduced 33.1% by the highest dose group (P < 0.05). The lesions of spatial memory were statistically corrected with the decrease of the NMDA-R affinities (P < 0.05).</p><p><b>CONCLUSION</b>The cholinergic lesion as well as the excitatory amino acid system alteration might attribute to the inferior ability in spatial learning and memory in dimethoate subchronically exposed rats.</p>

Relationship between plasma anti-metallothionein antibody and renal dysfunction in cadmium exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate whether renal dysfunction induced by cadmium is related to plasma anti-metallothionein antibody (anti-MT Ab) in workers occupationally exposed to cadmium.</p><p><b>METHODS</b>The male workers in a smeltery were selected as the subjects for the exposure and effect assessment. The urine cadmium (UCd), the blood cadmium (BCd) and the occupational cadmium intake (TTCd) served as the exposure indexes while the urine beta(2) microglobulin (Ubeta(2)-MG), the N-acetyl-beta-D-glucosaminidase (UNAG) and the urine albumin concentration (UALB) served as the effect markers for the renal dysfunction caused by the cadmium. The titer of the plasma anti-metallothionein antibody was determined with the enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The UCd (3.16 microg/g Cr), BCd (9.28 microg/L), Ubeta(2)-MG (81.17 microg/g Cr) and UALB (7.03 mg/g Cr) in the occupational cadmium exposure group were significantly higher than those in the control group and the Ubeta(2)-MG, UNAG and UALB as well as the occurrence rate of abnormality would be increased with the increase of the level of the occupational cadmium exposure. There was no significant difference in the titer of anti-MT Ab between the exposure group and the control group (P > 0.05). The titer of the anti-MT Ab would not be increased with the increase of the dosage of the exposure and had no significant correlation with BCd, UCd and TTCd (P > 0.05). The positive correlation were found between anti-MT Ab and UNAG as well as between anti-MT Ab and Ubeta(2)-MG in the exposure group with the correlation coefficient of 0.302 and 0.218 respectively. The workers with high level anti-MT Ab are more susceptible to cadmium nephrotoxicity than those with low anti-MT Ab with the odds ratio (OR) value of 4.200 and the 95% CI between 1.213 and 14.541 (P < 0.05).</p><p><b>CONCLUSION</b>There is a dose-effect relationship between cadmium exposure and renal dysfunction in workers occupationally exposed to cadmium, but no correlation is found between cadmium exposure and plasma anti-MT Ab. The workers occupationally exposed to the cadmium with higher level of anti-MT Ab are easier to suffer from renal dysfunction caused by cadmium. Plasma anti-MT Ab could be used as a biomarker of susceptibility in the workers exposed to cadmium.</p>

Application of metallothionein gene isoforms expression as biomarkers in cadmium exposure / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of metallothionein (MT) gene expression level in human peripheral blood lymphocytes (HPBLs) as a biomarker in cadmium exposure.</p><p><b>METHODS</b>The MT gene expression level in HPBLs of workers exposed to cadmium was examined using RT-PCR technique, and the exposure assessment and effect assessment were conducted in exposed workers.</p><p><b>RESULTS</b>The basal MT-1A, IE, IF, IX and MT-2A expression level in workers exposed to cadmium were significantly higher than those in the control group (P < 0.05). The basal MT-1A, IE, IF, IX and MT-2A expression level would be significantly increased with the increase of the blood cadmium (BCd) level (P < 0.05). There was a trend of increase for the mRNA expression of the basal MT-1A, 1E, IF, IX, MT-2A, especially for the mRNA expression of MT-1A and MT-2A (P < 0.05) with the increase of the level of the urine cadmium (UCd). There was a good dose-response relationship between basal MT-1A expression and UCd. The basal MT-1A, IE, IF, IX and MT-2A expression level were significantly correlated with BCd (P < 0.05) while the basal MT-1A, IF and MT-2A expression level were significantly correlated with UCd (P < 0.05). There were dose-effect relationships of BCd to the basal MT-1E, MT-1F, MT-1X and MT-2X expression level respectively and there were also dose-effect relationships of UCd, beta(2)-MG and the urine metallothionein to the basal MT-1A expression.</p><p><b>CONCLUSION</b>The expression of the MT gene isoforms in HPBLs can serve as the biomarker for the cadmium exposure and MT-1A can also serve as the effective biomarkers for the cadmium-induced renal toxicity.</p>

Heme oxygenase-1 expression and apoptosis induced by cadmium in human embryon kidney cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate apoptosis and expression of heme oxygenase-1 (HO-1) induced by cadmium in human embryonic kidney cells (HEK239T).</p><p><b>METHODS</b>The MTT method was used for determining the cell proliferation activity. The apoptosis was determined by the flow cytometry. The HO-l mRNA expression and protein level were detected by RT-PCR method and Western blot respectively.</p><p><b>RESULTS</b>The ratios of apoptosis in HEK239T cells were 11.90% +/- 0.28%, 9.27% +/- 1.73%, 9.79% +/- 0.67% and 8 .97% +/- 1.60% at the concentration of 5.0, 10.0, 20.0 and 40.0 micromol/L CdCl(2) respectively, higher than those in the control group (6.69% +/- 0.46%) with the significant difference (P < 0.01). The CdCl(2) of between 10 and 40 micromol/L could highly induce the expression of HO-1 of the human embryonic kidney cells. The expression would increase slowly till the flat stage with the increase of the dosage and then would decrease slightly over time.</p><p><b>CONCLUSION</b>The cadmium can induce the apoptosis of the human embryonic kidney cells and up-regulate the expression of HO-1.</p>