Effects of trophic 2,2′, 4,4′-tetrabromodiphenyl ether (BDE-47) exposure in Oreochromis niloticus: A multiple biomarkers analysis

Polybrominated diphenyl esters are emerging environmental contaminants with few toxicological data, being a concern for the scientific community. This study evaluated the effects of BDE-47 on the health of Oreochromis niloticus fish. The animals were exposed to three doses of BDE-47 (0, 0.253, 2.53, 25.3 ng g⁻¹) every 10 days, for 80 days. The BDE-47 affected the hepatosomatic and gonadosomatic index in female and the condition factor by intermediate dose in both sexes. The levels of estradiol decreased and the T4 are increased, but the vitellogenin production was not modulated in male individuals. Changes in AChE, GST, LPO and histopathology were observed while the integrated biomarker response index suggests that the lowest dose of BDE-47 compromised the activity of antioxidant enzymes. The oral exposure to BDE-47 in environmental concentrations is toxic to O. niloticus and the use of multiple biomarkers is an attribution in ecotoxicology studies and biomonitoring programs.     

母源性BDE-209暴露对仔鼠海马一氧化氮神经递质的影响

目的从一氧化氮神经递质角度探讨母源性BDE-209损伤仔鼠神经系统的可能机制。方法 3月龄wistar雌鼠自确定交配成功后随机分为实验组A、B、C、D和对照组E,通过胃灌方法建立自妊娠期至哺乳期的不同剂量BDE-209(100、300、600、1200mg/kg/d)的暴露模型,21天仔鼠断乳后各组随机选取10只仔鼠作为研究对象,应用光电比色法和放射免疫法分别测定各组仔鼠海马组织中一氧化氮(NO)含量、神经元型一氧化氮合成酶(nNOS)活性、环鸟苷酸(cGMP)含量。结果与对照组E相比,C、D组NO含量和nNOS活性明显增加(P<0.05);B、C、D组cGMP含量明显升高(P<0.05)。结论一定剂量的母源性BDE-209可能通过影响仔鼠NO神经信号递质系统影响其神经认知功能。     

Calorimetric evidence of interaction of brominated flame retardants with membrane model

The presence of polybrominated flame retardants in the environment seems to be increasing in the past decade. Considering the toxic effects of these pollutants, it is important evaluating the potential interaction with biological membranes for a risk assessment. In this study low and high brominated biphenyls and biphenyl ethers were used to investigate their interaction with biological membrane models constituted by liposomes, using differential scanning calorimetry (DSC) technique. The medium influence on membrane absorption was also assessed. The findings indicate that membrane interaction is controlled by compound structural characteristics. The membrane absorption is allowed by lipophilic medium; instead hydrophilic medium prevents membrane permeation.     

Exposure to polybrominated diphenyl ethers and male reproductive function in Greenland,Poland and Ukraine

Animal and a few human studies suggest that polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. The aim of the present study was to evaluate if male reproductive function was associated with serum level of PBDEs. We evaluated, in a cross-sectional study, the effects of environmental exposure to BDE-47 and BDE-153 on reproductive hormones and semen quality, including markers of DNA damage and apoptosis, in 299 spouses of pregnant women from Greenland, Poland and Ukraine. Adjusted linear regression models indicated no strong associations between BDE-47 or BDE-153 exposure and markers of male semen quality or reproductive hormones. In the largest study to date we demonstrate that BDE-47 and BDE-153 exposure was not associated with altered semen characteristics or reproductive hormones, indicating that male reproductive function is not affected by the exposure level of these compounds in fertile European or Arctic populations.     

BDE-209对子鼠甲状软骨IGF-1及IGF-1R表达的影响

目的通过母源性胃灌BDE-209 1500mg/kg,观察对子代大鼠甲状软骨细胞上IGF-1及IGF-1R的表达影响。方法将成年Wista雌性大鼠随机分为四组：实验组A（孕前期）、实验组B（孕期组）、实验组C组（孕前＆孕期组）、对照组D组（对照组）。将子鼠断乳后处死取甲状软骨,固定、包埋、切片后用免疫组化SP法观察细胞上IGF-1、IGF-1R的表达。结果母源性BDE-209胃灌可以引起子代甲状软骨细胞中IGF-1实验组A组和B组表达增加,与对照组比较都有统计学差异（P〈0.05）,而孕前＆孕期干预比单纯孕期干预子代大鼠的甲状软骨IGF-1表达有减少,差别有统计学意义;各实验组子代甲状软骨细胞中IGF-1R的表达与对照组对比有增加,差别有统计学意义。结论母源性BDE-209胃灌可以引起子代大鼠甲状软骨IGF-1、IGF-1R的表达改变。     

Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity

Thirteen structural analogs of the potent nonpolyglutamatable dihydrofolate reductase inhibitor N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, the para-aminobenzoyl moiety, or the 9,10-bridge were evaluated for the ability to inhibit human recombinant dihydrofolate reductase (DHFR), to utilize the reduced folate carrier (RFC) for influx, and to inhibit the growth of CCRF-CEM human leukemia cells in culture. In spectrophotometric assays of the kinetics of the reduction of dihydrofolate by DHFR in the presence of NADPH, these compounds had K(i) values ranging from 0.2 to 1.3pM, and thus were not greatly different in potency from the parent drug PT523. By comparison, the K(i) values of aminopterin (AMT), methotrexate (MTX), and 10-ethyl-10-deazaaminopterin (EDX) were 3.7, 4.8, and 11pM. In assays of competitive inhibition of [3H]MTX influx into CCRF-CEM cells, the K(i) values ranged from 0.21 to 7.3 micro M, as compared with 0.71, 5.4, and 1.1 micro M for PT523, AMT, and EDX. The K(t) for MTX was also re-analyzed and found to be 4.7 micro M, in better agreement with the literature than our previously reported value of 7.1 micro M. The IC(50) values of these compounds as inhibitors of the growth of CCRF-CEM cells after 72hr of drug exposure ranged from 0.53 to 55nM, and were qualitatively consistent with the other results.     

Mutations in the alpha-synuclein gene in Parkinson's disease among Indians

OBJECTIVE: To investigate the prevalence of G88C, G209A and any other mutation(s) in exons 3 and 4 of the alpha-synuclein gene in Indian patients with Parkinson's disease (PD). METHODS: A total of 169 PD patients comprising 18 familial, 3 juvenile, 48 early onset and 100 sporadic cases were included in this study. Genomic DNA was amplified by PCR using primers specific for Exons 3 and 4. Mutations at G88C and G209A were screened following restriction enzyme digestion of the PCR product. Direct PCR product sequencing of entire exons 3 and 4 was carried out for at least one proband each from the 10 familial cases. RESULTS: Neither G88C and G209A mutations nor any other mutation in exons 3 and 4 was found in the PD patients analysed. CONCLUSION: The G88C and G209A mutations do not seem to be the predominant genetic determinant of PD among Indians.     

Effect of brominated flame retardant BDE-47 on androgen production of adult rat Leydig cells

As one of the most abundant polybrominated diphenylethers (PBDEs) detected in adipose tissue and breast milk of humans, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is considered as a potential endocrine disruptor. The objective of this study is to explore whether environment-related level of BDE-47 could affect the androgen production in rat Leydig cells. Rat adult Leydig cells (ALCs) were treated with 10⁻⁸ to 10⁻⁴ M BDE-47 in vitro, the production of testosterone (T) and steroidogenic acute regulatory (StAR) protein level were determined. BDE-47 significantly increased basal T production and steroidogenic acute regulatory protein (StAR) level of ALCs after treatment with 10⁻⁴ M BED-47. Overall, LH (0.1 ng/ml) stimulated T production in ALCs by 6 folds, however it did not increase T production in BDE-47-treated ALCs when compared to untreated ALC. Both 8-Br-cAMP (for cAMP signaling) and 22R-hydroxycholesterol (22-diol, for P450 cholesterol side chain cleavage enzyme P450scc activity) significantly increased T production in ALCs treated with BDE-47 from 10⁻⁷ to 10⁻⁵ M. The results of this study indicate that environment-related level of BDE-47 in vitro increased T production in a dose-dependent manner. The stimulated effects of BDE-47 on StAR and P450scc might play key roles in BDE-47-mediated stimulation of T production.     

Bioaccumulation and behavioral effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in perinatally exposed mice

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants that have become pervasive environmental contaminants and may contribute to adverse health outcomes. We evaluated in mice the developmental neurotoxicity of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), one of the most abundant PBDE congeners detected in animal and human tissues. Female C57BL/6J mice were exposed to daily doses of 0, 0.03, 0.1 or 1 mg/kg beginning 4 weeks prior to conception, continuing through gestation and lactation, and ending at weaning on postnatal day (PND) 21. Levels of BDE-47 in blood, brain, liver and adipose tissues of dams were markedly increased after 4 weeks of exposure, around the time of mating, and continued to increase through the time of parturition. Blood levels of BDE-47 in the dosed dams were within the range reported in humans. BDE-47 tissue levels in the dams decreased between parturition and weaning, possibly reflecting mobilization during lactation. Brain BDE-47 levels in the offspring at PND 1 approached those of the dams at parturition. Perinatal exposure to BDE-47 resulted in significant dose dependent growth retardation, slower motor performance in several behavioral tests, and mice exposed to 1 mg/kg/day BDE-47 showed altered performance in the Morris water maze. There were no differences between groups in the numbers of pyramidal neurons in hippocampus CA1. These results document accumulation of BDE-47 in several organ systems following exposure to low-levels of BDE-47, and provide evidence that such exposure is associated with early behavioral deficits in exposed neonates.     

持续母源性经口暴露PBDE-209对其子代大鼠体液免疫毒性影响

目的 针对环境污染中十溴联苯醚(PBDE-209)对母婴健康存在潜在危害日益受到重视,研究经口胃灌十溴联苯醚(PBDE-209)对子代大鼠体液免疫毒性的影响.方法 经持续性母源暴露PBDE-209,观察其子代大鼠免疫器官脾脏组织结构变化、B淋巴细胞亚群、B淋巴细胞增殖转化功能、细胞因子(IL-4,IFN-γ)等变化,并检测总体血清中PBDEs原型化合物含量.结果 子代大鼠在出生2周时实验组CD19百分比低于对照组,差异有统计学意义(t=5.09,P＜0.01),实验组子代大鼠刺激指数(SI)与对照组比较差异无统计学意义(t=0.42,P=0.684).实验组的血清IFN-γ明显低于对照组(P＜0.01).实验组血清总体PBDE-209原型化合物含量为502 392 ng/glw,对照组血清总体PBDE-209原型化合物含量为46 206 ng/glw,实验组高出对照组10个数量级以上.实验组血清中其他PBDEs家族原型化合物,且总体含量均高于对照组.结论 母代持续暴露高剂量十溴联苯醚(PBDE-209)后,对子代体液免疫功能存在一定的毒性影响.