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OBJECTIVE: To investigate the effects of 1,2-dichloroethane( 1,2-DCE) on myelin basic protein( MBP),neuron specific enolase( NSE) and S100 protein in the plasma of SD rats. METHODS: Forty-eight specific pathogen free adult SD rats were randomly divided into control group,low-dose group and high-dose group,with 8 females and 8 males in each group. Rats were given 1,2-DCE orally at the dose of 0,27 and 79 mg / kg body weight every other day( every Wednesday,Monday and Friday) for 4 weeks. After 1,2-DCE administration,8 survived rats( half male and female) were randomly selected in each group. The plasma levels of MBP,NSE and S100 protein were measured using enzyme-linked immunosorbent assay. The blood and urinary samples were collected to assess the concentration of 1,2-DCE and its main metabolites( 2-chlorideacetic acid, 2-chlorideacetaldehyde and 2-chlorideethanol) by gas chromatography. The pathological changes of cerebrum and cerebellum were observed through optical microscope,and the expression of MBP was detected by immunohistochemistry. RESULTS: Rats in high-dose group showed abnormal behavior from the third day of1,2-DCE exposure and 6 rats( 2 females,4 males) died from 1,2-DCE intoxication. Rats in low-dose group and control group appeared normal and no death was observed. MBP level in the plasma of high-dose group was higher than that in the control group( P < 0. 05),but the levels of NSE and S100 protein in each group did not show significant statisticaldifference( P > 0. 05). 1,2-DCE and 2-chloroethanol in the urine were detected in the high-dose group,and were below detection limit in the other two groups. 2-Chloroacetic acid level in high dose-group was significantly higher than that in the low-dose group( P < 0. 05),and was below detection limit in the control group. 2-Chloroacetaldehyde in the urine of each group was below detection limit. 1,2-DCE and its 3 kinds of metabolites were not detected in the plasma of all rats. There was no obvious structural damage,bleeding,edema or necrosis found in the cortex and white matter of cerebrum and cerebellum. The expression of MBP in the choroid plexus epithelial cells were significantly enhanced in the lateral ventricle and the fourth ventricle of rats in the high-dose group,and slight enhanced in rats in the low-dose group. CONCLUSION: MBP may play a role in the toxic effect of 1,2-DCE.
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OBJECTIVE: To gain insight into the effect associated with cadmium toxicity in placenta and explore the reproductive toxicity of low level cadmium exposure. METHODS: Thirty-two specific pathogen free healthy female SD rats were randomly divided into 4 groups with 8 rats in each group. These were a control group and low-,medium- and highcadmium treated groups. Rats were treated with 0,1,3,9 mg / kg body weigh( bw) cadmium chloride by intragastric administration respectively. The treatment was once a day for 43 consecutive days as the one-generation reproductive toxicity experiment. On gestation day 20,the parental females were euthanized or delivered. The numbers of corpus luteum,implantations,live or dead fetuses,resorptions were all recorded and represented as reproductive toxicity index.Some placentas were prepared for proteomic analysis with difference gel electrophoresis method, some for histological analysis,some were analyzed by Western blot and immunohistochemistry methods. RESULTS: There was no statistical significance between low-cadmium treated group and control group in the changes of the body weights and reproductive toxicity index( P > 0. 05). The female rats showed different degrees of slow body weights gain from gavages day 19 in medium-and high-cadmium treated groups. According to the proteomic screening criteria in placenta,15 protein spots with a 1. 5-fold change relative to the controls in medium- and high-cadmium treated groups were identified. To validate the proteomics results,ATP-binding cassette,sub-family B,member 4( ABCB4) was examined by Western blot. The result showed that the expression of ABCB4 was significantly down-regulated in the cadmium treated groups( P < 0. 05).Moreover,there was a dose-response relationship between cadmium exposure and ABCB4 protein expressions( P < 0. 05).The histological analysis of placenta showed an increasing tendency towards degradation of cytotrophoblastic cells,hyperemia and decreased glycogen cells with increasing cadmium exposure. The subcellular localization of ABCB4 protein was mainly in the nucleus or cytoplasm in placenta. CONCLUSION: The above results demonstrated that the exposure to 1mg / kg· bw · d cadmium had not significant reproductive toxicity. The placenta is a target organ of cadmium toxicity.ABCB4 protein maybe involved in mediating the toxicity of cadmium in placenta.
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<p><b>OBJECTIVES</b>To determine the possible relationship between plasma potassium concentration and severity of acute trimethyltin chloride (TMT) poisoning and to assess the mechanism of TMT induced hypokalemia.</p><p><b>METHODS</b>SD rats were treated with various dosages of TMT (i.p.). All the indices were measured and analysed for determining their possible relations with plasma K+.</p><p><b>RESULTS</b>With increase of dosage, the plasma K+ level dropped rapidly, and deaths appeared more quickly. The LD50 of TMT (i.p.) was 14.7 mg/kgbw. In the low dosage group (10 mg/kgbw), the plasma K+ level dropped slowly with the lowest dosage on day 6 (4.85 mmol/L). It rose again on day 11 (5.06 mmol/L), and recovered on day 28. The poisoning signs corresponded with decline of the span of K+ level. The plasma Na+ level dropped half an hour after TMT treatment, but recovered 24 h later. In the high dosage group (46.4 mg/kgbw), the levels of plasma K+ and Na+ fell rapidly within half an hour (P < 0.05), the intracellular potassium concentration of RBC did not decrease obviously (P > 0.05), the activities of Na(+)-K(+)-ATPase and Mg(2+)-ATPase in RBC membrane were depressed remarkably (P < 0.01, P < 0.05, respectively), the plasma aldosterone concentrations rose as high as tenfold (P < 0.01), the arterial blood pH fell from 7.434 to 7.258 (P < 0.01), pCO2 was raised from 29.62 to 45.33 mmHg (P < 0.01). In the 24 h urine test, when rats were treated with TMT (21.5 mg/kgbw, i.p.), urine volume, urinary potassium, sodium and chloride increased significantly in comparison with those in the controls (P < 0.01).</p><p><b>CONCLUSION</b>TMT could induce hypokalemia in SD rats. The available evidence suggests that TMT can induce acute renal leakage of potassium. At the same time, a significant rise of plasma aldosterone may play an important role in promoting potassium leakage from kidney to result in severe hypokalemia with inhaling acid-base abnormalities produced, which aggravate the poisoning symptoms. In the end the rats would die of respiratory failure.</p>
Subject(s)
Animals , Female , Male , Rats , Hypokalemia , Injections, Intraperitoneal , Kidney Diseases , Lethal Dose 50 , Rats, Sprague-Dawley , Severity of Illness Index , Trimethyltin Compounds , Pharmacology , PoisoningABSTRACT
<p><b>OBJECTIVES</b>To study the contact allergenic activities of trichloroethylene (TCE) and its three metabolites trichloroacetic acid, trichloroethanol and chloral hydrate.</p><p><b>METHODS</b>A modified guinea pig maximization test (GPMT) was adopted. The skin sensitization (edema and erythema) was observed in trichloroethylene, trichloroacetic acid, trichloroethanol, chloral hydrate and 2,4-dinitrochlorobenzene.</p><p><b>RESULTS</b>The allergenic rate of TCE, trichloroacetic acid and 2,4-dinitrochlorobenzene was 71.4%, 58.3% and 100.0% respectively, and that of trichloroethanol and chloral hydrate was 0%. The mean response score of TCE, trichloroacetic acid and 2,4-dinitrochlorobenzene was 2.3, 1.1, 6.0 respectively. The histopathological analysis also showed an induction of allergenic transformation in guinea pig skin by both TCE and trichloroacetic acid.</p><p><b>CONCLUSION</b>TCE appears to be a strong allergen while trichloroacetic acid a moderate one. On the other hand, both trichloroethanol and chloral hydrate are weak sensitization potentials. Immunologic reaction induced by TCE might be postulated as the pathological process of this illness. Consequently, it is suggested that in the mechanism of Occupational Dermatitis Medicamentose-Like (ODML) induced by TCE, the chemical itself might be the main cause of allergy. As one of its metabolic products, trichloroacetic acid might be a subordinate factor.</p>