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 dimethoate on serum monoamines neurotransmitters in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of dimethoate on the monoamine Neurotransmitters, including norepinephrine (NE), epinephrine (E), serotonin (5-HT), dopamine (DA) and its metabolite (3, 4-hydroxyphenylacetic acid, DOPAC) in the serum of rats and furthermore to explore the non-cholinergic mechanism of organophosphate induced toxicity.</p><p><b>METHODS</b>Groups of rats were treated with saline and 38.9, 83.7 and 180 mg/kg dimethoate respectively and were decapitated at the different time course from 0.5 to 24 hours after the administration. The monoamines neurotransmitters were determined by the reverse-phase high-performance liquid chromatography with the electrochemical detection.</p><p><b>RESULTS</b>The serum concentrations of DA (8.42% - 248.42% of the control), DOPAC (17.22% - 68.21% of the control) increased, according with the DM dosage and the exposure time, while the levels of NE (9.65% - 38.26% of the control) and E (11.00% - 32.62% of the control) contents decreased at the same time.</p><p><b>CONCLUSION</b>These findings indicate that dimethoate induced toxic effects can alter the monoamine levels at the different dosage and the time exposure in the serum of rats. It suggests that some non-cholinergic mechanisms may be involved in the dimethoate intoxication.</p>

Relationship between the polymorphism of carboxylic esterases and genetic susceptibility to organophosphates pesticides exposure / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the relationship between the polymorphism of butyrylcholinesterase (BChE, EC 3.1.1.8) and paraoxonase (PonE, EC 3.1.8.1), and the individuals' genetic susceptibility to organophosphates pesticides (OPs) exposure.</p><p><b>METHODS</b>75 OPs exposure workers were selected to determine their BChE-K, PON-192 and PON-55 genotypes using PCR-RFLP. The accumulative symptom scores and the whole blood acetylcholinesterase activity (mmol x h(-1) x ml(-1)) were used as health index. Firstly, the health condition related to single gene site of the three gene loci was analyzed to determine which kinds of genotype were susceptible. Then, used the multiple variance analysis was to see if there existed interactions among these three gene loci. Finally, established the multi-factor linear regression equation, in which considered some other factors that might influence the health situation such as age, gender and the exposure time. According to the equation, could get the accumulative symptom scores of each kind of subpopulation of different genotypes.</p><p><b>RESULTS</b>The mean AChE activities of the exposed workers with BChE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) were 105.0 +/- 23.0, 84.4 +/- 16.4, 79.0 +/- 9.9, respectively; The accumulative symptom scores were 3.7 +/- 3.8, 9.2 +/- 3.0, 12.5 +/- 0.7, respectively. The AChE activities of the exposed workers with PON-192 genotype BB (37 cases), genotype AB (27 cases) and genotype AA (11 cases) were 116.8 +/- 15.1, 91.2 +/- 15.6, 72.3 +/- 21.4, respectively; The accumulative symptom scores were 2.0 +/- 3.2, 6.7 +/- 3.3, 9.7 +/- 1.8, respectively. Similarly, the AChE activities of the exposed workers with PON-55 genotype LL (70 cases) and genotype LM (5 cases) were 102.4 +/- 23.0, 82.8 +/- 22.0; The accumulative symptom scores were 4.5 +/- 4.2, 9.2 +/- 3.6, respectively. Single variance analysis showed that the accumulative symptom scores of the individuals with abnormal homozygote of these three gene loci were the highest, which indicated that they were most susceptible to OPs. Multiple variance analysis showed there were no interactions among the three gene loci. Age, gender and exposure time had no statistical significance, while genotypes of the three gene loci had statistical significance to health situation.</p><p><b>CONCLUSION</b>Genotypes of BChE-K, PON-192 and PON-55 are related to susceptibility to OPs exposure.</p>

Expression of M3 receptor gene in peripheral blood lymphocytes of workers exposed to dimethoate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the expression of muscarinic receptor M(3) gene in peripheral blood lymphocytes of workers exposed to organophosphorus pesticides (OPPs) and to explore its role in the adverse effects of OPPs.</p><p><b>METHODS</b>The lymphocytes of peripheral blood from 33 workers exposed to dimethoate and 15 control people were isolated and treated with saline and dimethoate respectively in vitro. RT-PCR technique was used to determine M(3) gene expression. Basal and inducible gene expression levels were measured.</p><p><b>RESULTS</b>There was no significant difference in basal gene expression level between exposed group and control group, while the inducible gene expression level was significantly higher in exposure group (1.92 +/- 1.07) than in control group (1.22 +/- 0.19) and basal level (1.49 +/- 0.45, P < 0.05). No differences in basal and inducible gene expression level were found between male and female people in both exposed and control group. The level of inducible M(3) gene expression increased with the increase in length of exposure time [< 5 a: (1.69 +/- 0.95), 5 - 25 a: (1.91 +/- 1.03), > 25 a: (2.09 +/- 1.25), the latter was significantly different from that of < 5 a (P < 0.05)].</p><p><b>CONCLUSION</b>After long-term exposure to OPPs, the basal M(3) receptor gene expression level in the exposed workers did not show any difference from the control group, but the inducible gene expression level (treated with dimethoate in vitro) was increased and related to the extent of exposure to dimethoate.</p>

Muscarine receptor gene expression in brain and peripheral blood lymphocytes of rats pretreated with dimethoate for 28 days / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the tolerance of rats induced by 28 day pretreatment with low dosage of dimthoate and the toxic effects challenged by higher dosage of dimethoate, and to investigate the change of M receptor and the mechanism of tolerance formation.</p><p><b>METHODS</b>SD rats were given 25 mg/kg dimethoate daily(sc) while control group was given saline daily instead for 28 days. The activity of whole blood acetylcholinesterase (AChE) was examined. On the 29th day three groups of administrated rats were challenged by saline solution, 50 mg/kg and 100 mg/kg dimethoate, respectively. The density and mRNA level of brain M(1), M(2) receptor were determined. Lymphocytes of peripheral blood were isolated, and basal, inducible M(3) gene expression were measured by RT-PCR.</p><p><b>RESULTS</b>During pretreatment, blood AChE activity decreased continually, it reached the lowest on the 13th day. And it decreased more after exposed to higher dosage of dimethoate. Brain AChE activity in the pretreated groups was lower than that in control group and decreased with the increase in challenging dosage. The density of M(1) receptor in negative control, pretreated, and 50, 100 mg/kg challenging groups were 979.15, 856.54, 539.46, 539.14 fmol/mg pro respectively. The change in relative levels of mRNA of M(1) receptor (2.59, 2.47, 2.20, 1.81) were consistent with the density of receptor but the level declined continually as the challenging dosage increased. The density of M(2) receptor were 507.38, 611.11, 548.42, 337.47 fmol/mg pro respectively, which were not obviously affected by pretreatment but decreased as the challenging dosage increased. The change in levels of M(2) receptor mRNA was not obvious. The basal gene expression of M(3) receptor mRNA was not different among all experimental groups while the inducible gene expression decreased with the increase in challenging dosage.</p><p><b>CONCLUSION</b>Low level dosage of dimethoate could induce animals to tolerate dimethoate toxicity. Reduction of M(1) receptor density which may be induced by the decrease in its gene expression may be the mechanism of tolerance. The change of M(3) receptor mRNA inducible expression in lymphocyte accorded with M(1) receptor mRNA expression in the brain.</p>

Protective effect of memantine on N-methyl-D-aspartate receptor in dichlorvos-poisoned rat brain / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the protective effect of memantine on the regulation of N-methyl-D-aspartate (NMDA) receptor in dichlorvos-poisoned rat brain, and to understand the mechanism of its role in organophosphate poisoning.</p><p><b>METHODS</b>SD rats were administrated dichlorvos (25 mg/kg, ip) then three groups were treated with memantine at doses of 5, 15 and 45 mg/kg respectively. The activity of acetylcholinesterase (AChE) and binding capacity of NMDA receptor with [(3)H]MK-801 were determined 16 h after dichlorvos injection.</p><p><b>RESULTS</b>The time of onset of toxic symptoms in 15, 45 mg memantine treated groups [(18.40 +/- 1.14) and (21.40 +/- 1.52) min respectively] was higher than that in dichlorvos alone group [(16.75 +/- 1.62) min]; the intensity of muscle fasciculation (1.60 +/- 1.14 and 0.80 +/- 0.84, respectively) was less than that in control group (2.85 +/- 0.37); the total score of poisoning symptoms (8.80 +/- 1.79 and 9.00 +/- 2.24 respectively) was also less than that in dichlorvos group (14.60 +/- 1.70). The AChE activities both in blood and brain of memantine treated groups were not significantly different from those in dichlorvos alone group. The affinity (Kd value) and density (Bmax value) of brain NMDA receptor in dichlorvos exposed rats [(75.55 +/- 7.87) nmol/L, (0.46 +/- 0.06) pmol/mg pro respectively] were higher and lower respectively than those in control group [(37.37 +/- 4.17) nmol/L, (0.62 +/- 0.04) pmol/mg pro respectively]. Lower level of memantine (5 and 25 mg/kg) could antagonize the dichlorvos-evoked down-regulation of [(3)H]MK-801 binding to NMDA receptor in rat brain [Bmax value: (0.55 +/- 0.07) and (0.64 +/- 0.07) pmol/mg pro; Kd value: (38.68 +/- 4.54) and (32.58 +/- 3.90) nmol/L respectively] while higher dose of memantine (45 mg/kg), the Bmax (0.45 +/- 0.06) pmol/mg pro and Kd (22.88 +/- 4.42) nmol/L of NMDA receptor were significantly decreased (P < 0.01).</p><p><b>CONCLUSION</b>Memantine in certain dose range could protect against the down-regulation of NMDA receptor in rat brain, and alleviate organophosphorus poisoning symptoms to some extent. The recovery of AChE activity inhibition wasn't involved in the treatment with memantine on dichlorvos poisoning, therefore, atropine and a proper AChE reactivator (an oxime) should be used clinically.</p>