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>