Effects of acrylonitrile on apoptosis of rat cerebral nerve cells.

The brain, especially the hippocampus, is sensitive to damage caused by anoxic chemicals. In this study, we established a rat model of acrylonitrile poisoning with administration by gavage, aiming to determine the influence of acrylonitrile on rat cerebral nerve cells. Transmission electron microscopy observation and TdT-mediated dUTP nick-end labelling (TUNEL) staining were used to explore preliminarily the apoptotic changes of cerebral nerve cells. The pathogenesis revealed by transmission electron microscopy indicated that apoptosis in the control group was more serious than that of the exposure groups. The results of TUNEL staining showed the apoptotic rate was significantly higher in the control group than that of other exposure groups. All the results indicated that acrylonitrile can inhibit the apoptosis of rat cerebral nerve cells, which is closely related to its animal carcinogenicity.

The value of APACHE II in predicting mortality after paraquat poisoning in Chinese and Korean population: A systematic review and meta-analysis.

BACKGROUND: The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is used to determine disease severity and predict outcomes in critically ill patients. However, the prognostic significance of APACHE after acute paraquat (PQ) poisoning remains unclear. The meta-analysis was aimed to study the value of APACHE II in predicting mortality in PQ-exposed Chinese and Korean patients. METHODS: Databases that included PubMed, Embase, Cochrane Library, and the Chinese National Knowledge Infrastructure were searched through August 2016. Studies using APACHE II to predict mortality in PQ-poisoned patients were selected. The odds ratio and weighted mean difference (WMD) were used to pool binary and continuous data. Additionally, we aggregated sensitivity, specificity, and other measures of accuracy. Statistical analyses were made using the Stata V.13.0 software. RESULTS: This study included 29 studies, and 25 studies evaluated APACHE II scores on admission. Pooled data showed that survivors had significantly lower total scores than nonsurvivors (WMD = -7.29, and I = 98.2%, both P <.05). The pooled sensitivity of an APACHE II score ≥5 for predicting mortality was 75% and the pooled specificity was 86%. The positive likelihood ratio (PLR) was 5.3 and the negative likelihood ratio (NLR) was 0.29. The pooled sensitivity of an APACHE II score ≥10 for predicting mortality was 88% and the pooled specificity was 84%. The pooled PLR and NLR was 5.5 and 0.15, respectively. CONCLUSION: This study showed PQ-poisoned nonsurvivors had significantly higher APACHE II score than did survivors. APACHE II scores satisfactorily predicted mortality.

The Cytotoxic Effect of the Benzene Metabolite Hydroquinone is Mediated by the Modulation of MDR1 Expression via the NF-κB Signaling Pathway.

BACKGROUND/AIMS: Benzene is a toxic chemical whose leukemogenic effects have been studied for decades. The mechanisms of benzene-induced toxicity and leukemogenicity are not fully understood, although the involvement of several pathways has been suggested, including oxidative stress, DNA damage, cell cycle regulation and programmed cell death. In the present study, we investigated the effect of hydroquinone (HQ), a major benzene metabolite, on the viability of bone marrow derived mesenchymal stem cells (BMSCs) and explored the underlying mechanisms. METHODS: First, we study the the effect of HQ on BMSCs cell viability, apoptosis and the expressions of MDR1 and NF-κB. Then we investigate the MDR1 on cell viability and cell apoptosis for BMSCs under HQ treatment. Finally, we studied the impact of nuclear factor κB (NF-κB) on the expression of MDR1. RESULTS: Our results showed that HQ decreased cell viability and promoted cell apoptosis of BMSCs, as determined by the MTT assay and flow cytometry. Western blotting and quantitative PCR showed that HQ downregulated the expression of the MDR1 gene by inhibiting the activation and nuclear translocation of the transcription factor NF-κB. Overexpression of MDR1 attenuated the inhibitory effect of HQ on cell viability in BMSC. CONCLUSION: The results of the present study suggest the involvement of the multidrug resistance membrane transporter MDR1 and the NF-κB pathway in the cytotoxicity of benzene and its metabolites. Further studies are necessary to clarify the role of the pathways involved and the crosstalk between them in mediating the effects of HQ in bone marrow progenitor cells.

Effects of low concentrations of benzene exposure on levels of platelet-associated antibodies and platelet parameters.

OBJECTIVE: To evaluate the impact of exposure to low concentrations of benzene on the platelet-associated antibodies and platelet parameters. METHODS: We carried out an analysis on 121 benzene-exposed workers and 110 healthy workers whose blood samples were collected and the levels of platelet-associated antibodies and platelet parameters were assessed. Benzene emissions were monitored over 5 years. RESULTS: Large-platelet cell ratios (P-LCR), platelet distribution width (PDW), and mean platelet volume (MPV) were significantly higher in benzene-exposed participants than in control participants. In participants who smoke cigarettes or drank alcohol, P-LCR, PDW, and MPV were more significantly elevated in the benzene-exposed group than in nonsmokers and nondrinkers. Platelet-associated immunoglobulin (PAIg) levels in benzene-exposed participants were higher than those in the control group, and PAIgA and PAIgM levels correlated with cumulative benzene exposure. CONCLUSIONS: Exposure to low concentrations of benzene can induce changes in PAIg levels and platelet parameters.

[The effects of acrylonitrile on T lymphocyte subsets and expression of toll-like receptor 4 in rats].

OBJECTIVE: To explore the effects of acrylonitrile on T lymphocyte subsets, expression of toll-like receptor 4 and related cytokines in rats. METHODS: Sixty-four Sprague-Dawley rats were randomly divided into 4 female groups and 4 male groups, and there were 8 rats in each group. Rats in each group were respectively given a single dose of 0, 5, 10 and 20 mg/kg acrylonitrile by gavage, once a day, 5 days a week, for 13 weeks. Blood and spleen T lymphocyte subsets was detected by flow cytometry, the mRNA expression of TLR4, IL-1ß and TNF-α was analyzed by real-time quantitative PCR, the protein expression of TLR4 was evaluated by Western blot. RESULTS: Compared with control group, the percentages of blood CD3, CD4 T cells in 20 mg/kg female group and CD4/CD8 ratio in 5, 10 and 20 mg/kg female groups was significantly decreased, CD8 T cells in 20 mg/kg group was significantly increased (P < 0.05 or P < 0.01), blood CD3 T cells in 5 mg/kg male group, CD4 T cells and CD4/CD8 ratio in 20 mg/kg male groups were lower than that of control group, CD8 T cells in 20 mg/kg make group was significantly in oreased (P < 0.05 or P < 0.01). Spleen CD4, CD8 T lymphocyte percentages and CD4/CD8 ratio in 20 mg/kg female group decreased significantly, CD8 T cells in 20 mg/kg male group was significantly increased (P < 0.05 or P < 0.01), spleen CD3, CD4, CD8 T cells in 20 mg/kg male group and CD4/CD8 ratio in 10, 20 mg/kg male groups was also significantly decreased, CD3 T cells in 20 mg/kg and CD8 T cells in 10, 20 mg/kg male groups were significantly increased (P < 0.05 or P < 0.01) (TLR4 mRNA was lower expressed in 5, 10 and 20 mg/kg male groups and 10 mg/kg female group (P < 0.05 or P < 0.01), and TLR4 protein in 5 mg/kg female group and 20 mg/kg male group was significantly lower than control group (P < 0.05). The expression level of IL-1ß mRNA was significantly decreased in 5, 10 and 20 mg/kg female group and 5, 10 mg/kg male group (P < 0.05 or P < 0.01), TNF-α mRNA was lower expressed in 10, 20 mg/kg female groups and 5, 10 mg/kg male groups (P < 0.01). CONCLUSION: Acrylonitrile may lead to the changes of CD3, CD4, CD8 T lymphocyte percentages and CD4/CD8 ratio in rat blood and spleen, and also significantly effected the expression level of TLR4 mRNA and protein together with the secretion of IL-1ß, TNF-α. This may cause effects on the cellular immune function.

[Occupational acute dimethylformamide poisoning: an analysis of 16 cases].

OBJECTIVE: To analyze the clinical features and diagnostic points of occupational acute dimethylformamide (DMF) poisoning and to explore the mechanism of occupational acute DMF poisoning. METHODS: A comprehensive analysis was performed on the clinical data of 16 cases of occupational acute DMF poisoning, including symptoms, signs, and laboratory testing results. RESULTS: The main clinical features of occupational acute DMF poisoning were digestive system impairments, especially abdominalgia. Hemorrhagic gastroenteritis was not found by gastroscopy. There was no significant correlation between the degree of abdominalgia and alanine aminotransferase level (r(s) = 0.109, P>0.05). CONCLUSION: Abdominalgia is recommended to be one of the reference indices for the diagnosis and degrading of occupational acute DMF poisoning, The mechanism of DMF poisoning remains unclear but it is considered to be related to methyl isocyanate, the intermediate product of DMF metabolism.

[The effects of benzene poisoning on expression of multidrug resistance 1 gene and P-glycoprotein in bone marrow mononuclear cells of C57BL/6 mice].

OBJECTIVE: To investigate the effects of benzene poisoning on the expression of multidrug resistance 1 (MDR1) gene and P-glycoprotein (P-gp) in the bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice. METHODS: C57BL/6 mice were randomly divided into control group (n = 24), low-dose group (n = 24), medium-dose group (n = 24), and high-dose group (n = 24) to receive corn oil, 25 mg/kg benzene, 50 mg/kg benzene, or 100 mg/kg benzene by gavage, once daily, 5 days/weeks, for 4 weeks. The mice were sacrificed on day 12, 26, or 29 of poisoning. Peripheral blood routine test was performed; real-time quantitative PCR was used to measure the MDR1 gene expression in BMMNCs; Western blot was used to measure the P-gp expression in BMMNCs. RESULTS: On day 12, the red blood cell count and hemoglobin level in the high-dose group were significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). On day 26, the white blood cell count in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). At each time point, the mRNA expression of MDR1 gene in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.01). On day 26, the P-gp expression in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group, and the P-gp expression in the medium-dose group was significantly lower than that in the low-dose group (P < 0.01 or P < 0.05). On day 29, the P-gp expression in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.05). CONCLUSION: Benzene poisoning can affect the expression of MDR1 gene and P-gp, which may be one of the mechanisms of benzene hematotoxicity.

[Influence of MDR1 gene C3435T on peripheral white blood cell counts in workers exposed to benzene].

OBJECTIVE: To explore the effects of MDR1 C3435T on the peripheral white blood cell counts in workers exposed to benzene. METHODS: One hundred and twenty-one benzene-exposed workers and 110 healthy controls without benzene exposure were enrolled in this study. White blood cell counts influenced by the polymorphism of MDR1 gene were analyzed. RESULTS: The frequency of MDR1 3435 C/C, C/T, T/T in healthy controls was 37.27%, 46.36%, 16.37%, respectively, and it was 38.84%, 41.33%, 19.83% in the benzene-exposed workers, respectively. The frequency of the MDR1 gene was also not significantly different between benzene exposed workers and controls. Subjects exposed to benzene with MDR1 3435 mutation genotype (T/T) had the significantly lower WBC [(5.46 ± 1.51) × 10(9)/L] than those carrying wild type (C/C) and heterozygous (C/T), whose WBC were (6.08 ± 1.28) × 10(9)/L (P = 0.044). CONCLUSION: P-glycoprotein encoded by MDR1 gene may be implicated into the hematotoxicity of benzene. Subjects carrying MDR1 3435 T/T genotype may have a higher risk of benzene poisoning.

[High-resolution melting: a analysis for genotyping of MDR1 C3435T in benzene-exposed workers].

OBJECTIVE: Using high resolution melting (HRM) to analysis MDR1 C3435T in people exposed to benzene. METHODS: Restriction fragment length polymorphism (RFLP) was utilized to detect the polymorphism of MDR1 3435 in 121 benzene-exposed workers, and the results were compared with the HRM in 10% samples and were confirmed with direct sequencing for six people in them. RESULTS: By direct sequencing, consistent results of benzene-exposed workers with RFLP or HRM were got. The new high resolution melting curve analysis is more efficient, more convenient, and cheaper than RFLP. CONCLUSION: High-resolution melting analysis provides a valid approach to efficiently detect DNA genetic diagnosis, which is suitable for detect susceptible genes in occupational surveillance.

[Application of micronucleus test of buccal mucosal cells in assessing the genetic damage of workers exposed to acrylonitrile].

OBJECTIVE: To investigate the application of micronucleus test of buccal mucosal cells in monitoring the genetic effect of acrylonitrile in the population exposed to the acrylonitrile. METHODS: Forty-one healthy male workers in a chemical factory in Shanghai were selected as the low concentration acrylonitrile exposed group while forty-seven healthy male workers in an acrylonitrile factory in Shanghai were selected as the intermediate concentration acrylonitrile exposed group. At the same time, thirty-one male workers who had no toxicant exposure and lived in the same community were selected as the control group. The micronucleus test in buccal mucosal cells and lymphocytes were used respectively for assessing the genetic damage status of these men. RESULTS: The rate of micronucleus in buccal mucosal cells in both acrylonitrile groups (the low concentration group: 3.68% +/- 2.72%; the intermediate concentration group: 4.00% +/- 2.38%) was significantly higher than that in the control group (2.03% +/- 2.20%) (P < 0.05). The rate of micronucleus in the intermediate concentration group (4.23% +/- 3.34%) was significantly higher than that in the control group (2.48% +/- 1.46%) (P < 0.05). There was the correlation between the micronucleus test of buccal mucosal cells and the micronucleus test of the lymphocytes in the peripheral blood in the acrylonitrile exposed population (r = 0.299-0.359, P < 0.05). CONCLUSION: The micronucleus test of buccal mucosal cells replacing the micronucleus test of the lymphocytes in the peripheral blood can be used as one of the screening indexes in the surveillance of the genetic damage in the acrylonitrile exposed population.

[Dynamic alterations of rat metabolic enzymes activities and liver damage in rat exposed to vinyl chloride monomer].

OBJECTIVE: Study the alterations of metabolic enzyme activities and liver functions induced by vinyl chloride monomer(VCM) and to explore the relationship between metabolic enzyme activities and liver functions. METHODS: Animals were administered VCM for 12 weeks in doses of 0, 5, 10, 20 mg/kg (i.p.), and were victimized at week of 3rd, 6th, 9th, 12th. The activities of enzymes were determined using spectrophotography. The indexes of liver functions were assayed by automatic biochemistry analyzer. The histopathological alterations of rat livers were observed. RESULTS: The activities of ALDH, CYP2E1, GSTs, were significantly different between groups, in addition, those differences can also be seen with the increase of experiment time. There was negative correlation between ALP and ADH (r = -0.649). CONCLUSION: The degree of liver damage induced by VCM could be associated with the activities of liver metabolic enzymes. It was suggested that there was slight correlation between enzyme activities in serum and enzyme activities in liver.

[Study on mitochondrial DNA damage in peripheral blood nucleate cells of the workers exposed to acrylonitrile].

OBJECTIVE: To study the potential aging effect on workers exposed to acrylonitrile (ACN). METHODS: The deletion rates of mitochondrial DNA (mtDNA) in peripheral blood nucleate cells of 47 exposed workers and 47 non-exposed workers (as control), as well as 12 old people and 12 young people were measured with polymerase chain reaction (PCR). RESULTS: The positive rates of mtDNA deletion in peripheral blood nucleate cells were 17.02% in the workers exposed to ACN and 25.00% in group of old people. However, the mtDNA deletion was not detected in the control group and young people. CONCLUSIONS: ACN could induce mtDNA deletion in peripheral blood nucleate cells of the exposed workers. There may be a potential molecular effect of occupational ACN exposure on workers' aging.