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Decabromodiphenyl ethane (DBDPE) is a kind of new brominated flame retardants, which is widely used as a replace of decabromodiphenyl ether in electronic appliances, textiles and other goods. This review summarizes environmental levels and body burden of human beings of DBDPE in recent years. The data shows that the concentration of DBDPE in the environment and human tissues shows an upward trend. According to limited experiments about its toxicity, DBDPE shows similar toxicity to decabromodiphenyl ether. DBDPE can interfere thyroid hormones balance, and cause damage to liver, reproductive development, kidney, et al, which implies that DBDPE might be another new persistent organic pollutant. Further researches are needed.
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<p><b>OBJECTIVE</b>This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane (DBDPE).</p><p><b>METHODS</b>In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 (CYP) levels and activities and uridinediphosphate-glucuronosyltransferase (UDPGT) activities were investigated. Liver and thyroid glands were observed.</p><p><b>RESULTS</b>There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and fT3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency.</p><p><b>CONCLUSION</b>DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by AhR and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis.</p>
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Objective To investigate the expression of P2X7 receptor (P2X7R) and the effect of P2X7R agonist 2'-3'-O-(4-benzoyl-benzoyl) ethane adenosine triphosphate three amine salt (BzATP) on cell growth and apoptosis in non-small cell lung cancer A549 cells,and to explore the related mechanism.Methods The expression of P2X7R in A549 cells was detected by immunofluorescence.Cells were treated with different concentrations (150,300,600 μmol/L) of BzATP.Cells untreated with BzATP were used as control group.3-(4,5-dimethyl-2-thiazoly)-2,5-diphenyl-2H-tetrazolium bromide (MTF) assay and Hoest33342 staining were respectively used to detect cell viability and apoptosis.Enzyme-linked immunosorbent assay (ELISA) was uesd to detect the concentration of tumor necrosis factor-α (TNF-α) of cell culture supernatants.The expressions of nuclear factor-κB (NF-κB) p65,inhibitor of α of NF-κB (IκBα) and the phosphorylation of inhibitor of α of NF-κB (phospho-IκBα) were detected by Western blotting.Results P2X7R was expressed on the cell membrane of A549 cells.Survival rate of A549 cell was significantly decreased with the concentrations of BzATP at 300 and 600 μmol/L [(67.87 ± 8.98) ％,(44.73 ± 6.92) ％],compared with the control group (98.60 ± 1.44) ％,the differences were statistically significant (t =4.481,P =0.027;t =3.920,P =0.038).BzATP promoted apoptosis,and increased the concentration of TNF-α of supernatant at 300 and 600 μmol/L [(57.35 ±6.41) pg/ml,(78.63 ± 11.33) pg/ml],compared with the control group (42.56 ±0.37) pg/ml,the differences were statistically significant (t =6.410,P =0.035;t =11.330,P =0.005).In addation,the expressions of NF-κB p65 and IκBα were respectively downregulated and upregulated by BzATP,while the expression of phospho-IκBα was not significantly altered.Conclusion P2X7R is expressed on A549 cell membrane.BzATP can inhibit cell proliferation and induce the apoptosis of A549 cells,and the mechanism of action may be related to promoting the release of TNF-α and inhibition of NF-κB pathway.
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AIM:To investigate the effects of ethane 1,2-dimethanesulfonate (EDS) preconditioning on renal ischemia/reperfusion (I/R) injury in male Sprague-Dawley (SD) rats.METHODS: Male SD rats (n=48) were ran-domly assigned to 6 groups:blank, sham, I/R, EDS+I/R, EDS+testosterone (TST) +I/R, and castration (Cast)+I/R.The renal pedicles were bilaterally occluded with a microvascular clamp for 45 min to establish renal I/R-induced in-jury model.Bilateral orchiectomy was conducted 2 weeks before surgery .EDS (75 mg/kg) was intraperitoneally injected 5 d before operation .Blood samples were collected 24 h after reperfusion from the vena orbitalis posterior plexus .Luteinizing hormone (LH), TST, serum creatinine (SCr), blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1) were detected.The renal tissues were harvested to measure the level of TNF-αand the expression of Fas mRNA and caspase-3 protein.RESULTS:Serum TST levels in EDS +I/R group and Cast +I/R group were below the minimum detectable threshold.Compared with other groups , the rats in EDS+I/R group and Cast +I/R group had higher levels of SCr , BUN and KIM-1 (P0.05), but KIM-1 level in EDS+I/R group was lower than that in Cast +I/R group (P<0.05).After reper-fusion for 24 h, the levels of TST and LH in EDS +I/R group, Cast+I/R group and EDS+TST+I/R group were lower than those 1 h before operation (P<0.05).Compared with Cast+I/R and I/R group, the TNF-αlevel and expression of Fas mRNA and caspase-3 protein were significantly decreased in EDS +I/R group ( P<0.05 ) .CONCLUSION: EDS preconditioning substantially reduces the serum TST level , thus attenuating I/R-induced acute renal injury .TNF-α-induced Fas/FasL pathway may be involved in this process .
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ObjectiveTo investigate the expression of thyrotropin-releasing hormone receptor (TRH-R) type-1and type-2 in ethane dimethanesulphonate (EDS)-treated rat testis, and to discuss the significance of its expression in Leydig cells.Methods To make the injured testis Leydig cells rat model with EDS treatment. Western blotting, immunohistochemical ABC and immunofluorescence double labeling methods were used to detect the expression and location of TRH-R1 and R2 in the testicular tissues of EDS-treated-day 2,day 7,day 14,day 21 and day 28 rat mode, respectively. Results Western blotting results showed that the positive immunochemical staining was not found in the testicular tissues of the EDS-treated day 2 to day 14, on the other hand,they were found in EDS-treated-21 day and EDS-treated-28 day. Immunohistochemistry demonstrated that TRH-R1 and R2 expressed in the spindle-shaped cells reappeared around seminiferous tubules of post-EDS 21 days and 28 days groups. Immunofluorescence double labeling confirmed that these TRH-R1 and R2 positively stained cells were newly regenerated progenitor Leydig cells.Conclusion TRH-R1 and R2 are involved in the regeneration of Leydig cells in EDS-treated rat testis, and they may exert functions in the proliferation and differentiation of adult type Leydig cells.
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Objective To evaluate the serum organochlorine pesticides residues levels in breast cancer pa-tients with different estrogen receptor(ER). Methods 93 patients of breast cancer from Fengnan districtand 65 pa-tients from Tanghai county in Tangshan were selected,whose ER were detected by pathology and serum organochlo-fine pesticides (DDTs and HCHs) levels were detected and compared with gas chromatography/electron capture. Results The orders of detection rate of HCH isomer in breast cancer patients in two areas were β-HCH >δ-HCH > α-HCH >γ-HCH. The orders of detection rate of DDT isomer in breast cancer patients in two areas were PP'-DDE > PP'-DDT > OP'-DDT > PP'-DDD. The serum levels of β-HCH, PP'-DDE in breast cancer patients in two are-as were positively correlated with age (r=0.272 ,0.330 , P<0.01) or BMI (r=0.312,0.187, P <0.01, <0.05). There were statistical differences in the serum β-HCH,δ-HCH,PP'-DDE levels between the estrogen receptor posi-tive breast cancer patients and the estrogen receptor negative breast cancer patients in two areas (P<0.05 for each). Conclusion The serum organochlorine pesticides residues levels in breast cancer patients with positive es-trogen receptor are higher than that with negative estrogen receptor, implicating that breast cancer is dependent on es-trogen. The cause of breast cancer is likely due to estrogen-like effect of serum organochlorine pesticides residues.
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Experiments, using CO intoxicated male Sprague-Dawley rats, were carried out (1) to see the change of the oxygen tree radical reaction according to partial pressure of oxygen, and (2) to assess the effectiveness of superoxide dismutase (SOD) activity, malondialdehyde (MDA), and ethane as a parameter of the reaction. Ethane was measured in exhaled breath anti SOD activity and MDA In brain tissue. Experimental group consist of (1) Control group (=breathing with air[ambient air]), (2) HBO group (=exposed to hyperbaric oxygen(HBO, 3ATA, l00%] after all breath), (3) CO-Air group (=exposed to CO [3,970 ppm] after air breath followed by air breath), (4) CO-HBO group (=exposed to CO after air breath followed by HBO treatment), and (5) CO group (=exposed to CO after air breath, only for SOD activity & MDA measuring). Amount of ethane exhaled during 30 minutes of HBO treatment after GO exposure was significantly greater than those of all the other groups (p-value= .002) , suggesting more oxygen free radical reaction is taken place in CO intoxicated rats treated with higher partial pressure of oxygen. The long-term follow-up studies are required to differentiate the adverse effects of HBO treatment from the sequelae of CO poisoning itself, and to develop the preventive measures for the adverse effect of HBO treatment. And there was no significnat difference among the five groups in SOD activity and MDA measuring (p-value>.05). This result may be accounted for the rapid recovery of SOD activity and the metabolic degradation and excretion of MDA in a short time. In conclusion, measurement of ethane in exhaled breath is more effective than those of SOD activity and MDA as a parameter to assess the oxygen free radical reaction produced by HBO treatment for CO poisoned rats as a whole
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Animals , Humans , Male , Rats , Brain , Carbon Monoxide , Carbon , Ethane , Follow-Up Studies , Malondialdehyde , Oxygen , Partial Pressure , Poisoning , Rats, Sprague-Dawley , Superoxide DismutaseABSTRACT
In vivo ethane production in rats was used as an index of oxygen toxicity. The rats were allocated to four exposure conditions; hyperbaric oxygenation (HBO=5 ATA, 100% O2), normobaric oxygenation (NBO=1 ATA, 100% O2), hyperbaric aeration (HBA=5 ATA, 21% O2) and normobaric aeration (NBA=1 ATA, 21% O2). After 120 minutes of exposure, the rats exposed to high concentration and/or high pressure oxygen exhaled significantly larger amounts of ethane than those exposed to NBA, and the differences in ethane production between any two groups were statistically significant (p<0.01). This finding supports the hypothesis that hypothesis that hyperoxia increase oxygen free-radicals and the radicals produce ethane as a result of lipid peroxidation. It is notable that the ethane exhalation level of the HBA group was significantly higher than that of the NBO group. This difference could not be accounted for by the alveolar oxygen partial pressure difference between the two groups.
Subject(s)
Animals , Rats , Ethane , Exhalation , Hyperbaric Oxygenation , Hyperoxia , Lipid Peroxidation , Oxygen , Partial PressureABSTRACT
By means of histological and immunohistochemical methods,effects of a singleintraperitoneal injection of ethane dimethanesulphonate(EDS,75 mg/kg bodyweight)on the hypothalamo-pituitary-testicular axis of the rat were observed inthis study.Three days after administration of EDS,Leydig cells were eliminated;some LH cells in pituitary became larger or decreased in immunoreactivity;but nosignificant change could be found in hypothalamic GnRH system.Seven days afterEDS,degeneration of spermatogenic epithelium was marked,the staining intensity ofLH cells was generally reduced,the number of GnRH immunorcactive neurons inthe hypothalamus as well as the density and staining intensity of GnRH fibers andterminals in the median eminence were significantly diminished.Testosteronereplacement increased the number of late spcrmatids in testis and restored theabove-mentioned changes in the hypothalamus and pituitary.These results indicate that following administration of EDS,1)spermatogenesisdamage is resulted from destruction of Leydig cells and cessation of testosterone secretion;2)respective hormone release from hypothalamic GnRH system andpituitary LH cells is increased;3)loss of testosterone negative feedback is themajor factor responsible for the enhancement of secretory activity of the hypotha-lamo-pituitary axis;and that 4)EDS can be a useful experimental tool forstudying hypothalamo-pituitary-testiculer axis and intratesticular local regulation.