Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice

BACKGROUND Decabromodiphenyl ether(BDE-209)is the most commonly used brominated flame retardant.Recently,BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity,insulin resistance(IR),type 2 diabetes mellitus,and hypertension.AIM To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice.METHODS Adult male C57BL/6 mice were randomly divided into high,medium-high,medium,medium-low,and low dose BDE-209 groups,and a control group(n=6 per group),which received 1000,800,600,450,300,and 0 mg/kg BDE-209,respectively.After BDE-209 exposure for 60 d,the mice were fasted overnight,and then sacrificed to obtain tissues.An automatic biochemical analyzer was used to detect serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C);enzymelinked immunosorbent assay kits were used to detect fasting serum insulin(FINS),leptin(LEP),and adiponectin(Adp)levels;a blood glucose meter was used to detect fasting blood glucose(FBG).Morphological changes of the liver were observed by hematoxylin and eosin staining.Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid(mRNA)and protein levels,respectively,of LEP,Adp,and peroxisome proliferators activated receptor-γ(PPARγ)in mouse liver and adipose tissues.RESULTS There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure(P<0.05).After 60 d of exposure,the weight of liver and adipose tissues in the exposure groups were greater than that of the control group(P<0.05).The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high,mediumhigh,and medium dose BDE-209 groups.The levels of FINS,insulin sensitivity index,Adp,and HDL-C were decreased in the BDE-209 group compared with the control group,as were the mRNA and protein levels of Adp in liver and adipose tissues(P<0.05).Serum level of FBG and LEP were higher in the BDE-209 group than in controls.TC,TG,and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγin liver and adipose tissues were higher than those in the control group(P<0.05).Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups(P<0.05).CONCLUSION BDE-209 increases the body weight,fat and liver tissue weight,TC,TG,and LDLC,reduces HDL-C,and causes IR in mice,which may be related to activating the PPARγreceptor.

Thyroid disruption by technical decabromodiphenyl ether (DE-83R) at low concentrations in Xenopus laevis

Decabromodiphenyl ether （decaBDE）,as a flame retardant,is widely produced and used.To study the thyroid disruption by technical decaBDE at low concentrations,Xenopus laevis tadpoles were exposed to technical decaBDE mixture DE-83R （1-1000 ng/L） in water from stage 46/47 （free swimming larvae,system of Nieuwkoop and Faber） to stage 62.DE-83R at concentration of 1000 ng/L significantly delayed the time to metamorphosis （presented by forelimb emergence,FLE）.Histological examination showed that DE83R at all tested concentrations caused histological alterations-multilayer follicular epithelial cell and markedly increased follicle size accompanied by partial colloid depletion and increase in the peripheral colloid vacuolation,in thyroid glands.All tested concentrations of DE-83R also induced a down-regulation of thyroid receptor mRNA expression.These results demonstrated that technical decaBDE disrupted the thyroid system in X.laevis tadpoles.Analysis of polybrominated diphenyl ethers （PBDEs） （sum of 39 congeners） in X.laevis indicated that mean concentrations of total PBDEs in X.laevis exposed to 1,10,100,1000 ng/L were 11.0,128.1,412.1,1400.2 ng/g wet weight,respectively.Considering that PBDEs burden of X.laevis tadpoles was close to PBDEs levels in amphibians as reported in previous studies,our study has raised new concerns for thyroid disruption in amphibians of technical decaBDE at environmentally relevant concentrations.

Debrominated and methoxylated polybrominated diphenyl ether metabolites in rainbow trout(Oncorhynchus mykiss) after exposure to decabromodiphenyl ether

Decabromodiphenyl ether （BDE209） is the primary component in a commonly used flame retardant. Previous studies had proved that BDE209 itself was not toxic, while its metabolites including debrominated diphenyl ethers （De-BDEs） and methoxylated brominated diphenyl ethers （MeO-BDEs） posed a potential threat to organisms. Many studies had indicated that BDE209 could metabolize quickly in mammals, but lacking in the basic data about the metabolism of BDE209 in fish. In the present study, two replicate treatment groups of rainbow trout （Oncorhynchus rnykiss） were exposed to BDE209 via a single intraperitoneal injection approximately 100 and 500 ng/g, respectively. Muscle, liver and blood samples were collected to analyze the specific metabolites on day 1 and day 28 post injection. The highest concentration of BDE209 was detected in muscle tissues, from 796.1 ng/g wet weight （day 1） to 687.1 ng/g wet weight （day 28） in high dose group, suggesting that BDE209 could accumulate slightly in muscle tissues. However, BDE209 was not detected in the blood for all treatments. Most congeners of De-BDEs were found in muscle and liver tissues, with the highest concentration in the liver. The main De-BDEs were nona-, octa-, hepta- and penta-De-BDEs. A total of seven MeO-BDE metabolites were observed among different fish tissues. Blood had the highest contribution of the MeO-BDE metabolites. Each MeO-BDE congener increased over the 28 days. These results in contrast to other studies suggested possible species-specific differences in metabolic abilities.

Removal of decabromodiphenyl ether （BDE-209） by sepiolite-supported nanoscale zerovalent iron

Nanoscale zerovalent iron （nZVI） synthesized using sepiolite as a supporter was used to investigate the removal kinetics and mechanisms of decabromodiphenyl ether （BDE-209）. BDE-209 was rapidly removed by the prepared sepiolite-supported nZVI with a reaction rate that was 5 times greater than that of the conventionally prepared nZVI because of its high surface area and reactivity. The degradation of BDE-209 occurred in a stepwise debromination manner, which followed pseudo- first-order kinetics. The removal efficiency of BDE-209 increased with increasing dosage of sepiolite-supported nZVI particles and decreasing pH, and the efficiency decreased with increasing initial BDE-209 concentrations. The presence of tetrahydrofuran （THF） as a cosolvent at certain volume fractions in water influenced the degrada- tion rate of sepiolite-supported nZVI. Debromination pathways of BDE-209 with sepiolite-supported nZVI were proposed based on the identified reaction intermedi- ates, which ranged from nona- to mono-brominated diphenylethers （BDEs） under acidic conditions and nonato penta-BDEs under alkaline conditions. Adsorption on sepiolite-supported nZVI particles also played a role in the removal of BDE-209. Our findings indicate that the particles have potential applications in removing environ- mental pollutants, such as halogenated organic contami- nants.

Debromination of decabromodiphenyl ether by organo-montmorillonitesupported nanoscale zero-valent iron: Preparation, characterization and influence factors

An organo-montmorillonite-supported nanoscale zero-valent iron material （M-NZVI） was synthesized to degrade decabromodiphenyl ether （BDE-209）. The results showed that nanoscale zero-valent iron had good dispersion on organo-montmoriUonite and was present as a core-shell structure with a particle size range of nanoscale iron between 30-90 nm, characterized by XRD, SEM, TEM, XRF, ICP-AES, and XPS. The results of the degradation of BDE-209 by M-NZVI showed that the efficiency of M-NZVI in removing BDE-209 was much higher than that of NZVI. The efficiency of M-NZVI in removing BDE-209 decreased as the pH and the initial dissolved oxygen content of the reaction solution increased, but increased as the proportion of water in the reaction solution increased.

Alterations of endogenous metabolites in urine of rats exposed to decabromodiphenyl ether using metabonomic approaches

There is large usage of polybrominated diphenyl ethers （PBDEs） especially for decabromodiphenyl ether （BDE-209, Deca-BDE） in controlling the risks of fire. The toxicological effects of PBDEs are worth being concerned about. Female SD rats were daily gavaged with BDE-209 ether at the dose of 100 mg/kg for 20 days. Histological observation was performed for the screening of the target organs for BDE-209 exposure. The distribution and metabolism of PBDEs in the exposed main organs were evidenced by HRGC-HRMS. Alterations of the endogenous metabolite concentrations in urine were investigated using metabonomic approaches based on IH NMR spectrum. Histopathological changes including serious edema in kidney, hepatocellular spotty necrosis and perivasculitis in liver indicated that BDE-209 caused potential influences on endogenous metabolism in the exposed liver and the kidney. BDE-209 was found to be highly accumulated in lipid, ovary, kidney and liver after 20 days＇ exposure. Occurrence of other lower brominated PBDEs in the rats demonstrated that reductive debromination process happened in vivo. Hydroxylated and methoxylated-BDEs, as metabolism products, were also detected in the rat tissues. A total of 12 different endogenous metabolites showed obvious alterations in urine from the exposed rats, indicating the disturbance of the corresponding internal biochemical processes induced by BDE-209 exposure. These findings in vivo suggested the potential health risk might be of concern due to the toxicological effects of BDE-209 as a ubiquitous compound in the environment.

Improved rhizoremediation for decabromodiphenyl ether(BDE-209)in E-waste contaminated soils

An experiment was conducted to improve rhizoremediation for decabromodiphenyl ether(BDE-209)contaminated soil from typical E-waste dismantling areas.Plants of ryegrass(Lolium perenne L.)and rice(Oryza sativa L.)were cultivated in aged-contaminated(initial concentration of 346.3μg BDE-209·kg^(-1))and freshly-spiked(initial concentration of 3127μg BDE-209·kg^(-1))soils,coupling with the agricultural modification strategies of compost addition and/or arbuscular mycorrhizal fungi(AMF)infection,respectively.60 days’growth of ryegrass significantly facilitated the dissipation of BDE-209,with the most effective in its rhizosphere in treatment inoculated with AMF;the BDE-209 dissipation rates achieved 51.9% and 22.8% in rhizosphere,and 43.5% and 19.8% in non-rhizosphere,for aged-contaminated and freshlyspiked soils,respectively.120 days’growth of rice with simultaneous inoculation of AMF and addition of compost was the most effective in facilitating BDE-209 dissipation in agedcontaminated soil,with the removal rates of 53.3% and 48.1% in rhizosphere and nonrhizosphere soils respectively;while for freshly-spiked soils,the most effective removal was achieved by compost addition only,with the BDE-209 dissipation rates of 27.9% and 26.6% in rhizosphere and non-rhizosphere soils,respectively.High throughput sequencing analysis of rhizosphere soil DNA showed that responses in microbial communities and their structure differed with plant species,soil pollution dose,AMF inoculation and/or compost addition.Actinomycetales,Xanthomonadales,Burkholderiales,Sphingomonadales,Clostridiales,Cytophagales,Gemmatimonadales and Saprospirales were the sensitive responders and even possibly potential functional microbial groups during the facilitated removal of BDE-209 in soils.This study illustrates an effective rhizoremediation pattern for removal of BDE-209 in pollution soils,through successive cultivation of rice and followed by ryegrass,with rice growth coupled with AMF inoculation and compost addition,while ryegrass growth coupled with AMF inoculation only.

Mechanism of Deca-BDE-induced apoptosis in Neuro-2a cells:Role of death-receptor pathway and reactive oxygen species-mediated mitochondrial pathway

Decabromodiphenyl ether（BDE-209） is a prevalent polybrominated diphenyl ether（PBDE）congener known to have neurotoxicity. Effects of BDE-209 on Neuro-2a cells were performed in the present study and the possible apoptotic pathway was discussed. Results indicated that BDE-209 induced Neuro-2a cell apoptosis, increased the protein expression of Fas and Fas-associated death domain-containing protein（FADD） and activated the caspase-8 and-3activities in a concentration-dependent manner, inferring the death-receptor pathway was involved in the apoptotic process. Meanwhile, BDE-209 exposure increased the Bax/Bcl-2 ratio and decreased the cellular mitochondrial membrane potential（MMP） which led to cytochrome C released to the cytoplasm. The intracellular caspase-9 was elevated simultaneously,which caused downstream caspase cascade and triggered cell apoptosis. Moreover, BDE-209 exposure increased cellular reactive oxygen species（ROS） level in a concentration-dependent manner and the addition of N-acetyl-L-cysteine（NAC）, known as ROS scavengers, obviously reduced the apoptotic rate and a positive relationship was observed between the degree of apoptosis blocking and the loss of MMP and ROS production. We thus concluded that BDE-209 induced Neuro-2a cell apoptosis via the combination of the death-receptor signaling pathway and the mitochondrial signaling pathway. The elevated ROS production was considered to magnify the intracellular apoptosis signal and played a crucial role in apoptosis of Neuro-2a cells induced by BDE-209.