-
Liqiong Song,
Wei Xia,
Zhao Zhou,
Yuanyuan Li, Yi Lin,
Jie Wei,
Zhengzheng Wei,
Bing Xu,
Jie Shen,
Weiyong Li,
Shunqing Xu
[show abstract]
[hide abstract]
ABSTRACT: Phenolic estrogen pollutants, a class of typical endocrine-disrupting chemicals, have attracted public attention due to their estrogenic activities of imitating steroid hormone 17β-estradiol (E(2)) effects. Exposure to these pollutants may disrupt insulin secretion and be a risk factor for type 2 diabetes. In this study, we investigated the direct effects of phenolic estrogen diethylstilbestrol (DES), octylphenol (OP), nonylphenol (NP), and bisphenol A (BPA) on rat pancreatic islets in vitro, whose estrogenic activities were DES>NP>OP>BPA. Isolated β-cells were exposed to E(2), DES, OP, NP, or BPA (0, 0.1, 0.5, 2.5, 25, and 250 μg/l) for 24 h. Parameters of insulin secretion, content, and morphology of β-cells were measured. In the glucose-stimulated insulin secretion test, E(2) and DES increased insulin secretion in a dose-dependent manner in a 16.7 mM glucose condition. However, for BPA, NP, or OP with lower estrogenic activity, the relationship between the doses and insulin secretion was an inverted U-shape. Moreover, OP, NP, or BPA (25 μg/l) impaired mitochondrial function in β-cells and induced remarkable swelling of mitochondria with loss of distinct cristae structure within the membrane, which was accompanied by disruption of mRNA expression of genes playing a key role in β-cell function (Glut2 (Slc2a2), Gck, Pdx1, Hnf1α, Rab27a, and Snap25), and mitochondrial function (Ucp2 and Ogdh). Therefore, these phenolic estrogens can disrupt islet morphology and β-cell function, and mitochondrial dysfunction is suggested to play an important role in the impairment of β-cell function.
Journal of Endocrinology 09/2012; 215(2):303-11. · 3.55 Impact Factor
-
Zhengzheng Wei,
Liqiong Song,
Jie Wei,
Tian Chen,
Jun Chen, Yi Lin,
Wei Xia,
Bing Xu,
Xuguang Li,
Xi Chen,
Yuanyuan Li,
Shunqing Xu
[show abstract]
[hide abstract]
ABSTRACT: Di-(2-ethylhexyl)phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. We investigated the consequences of maternal exposure to DEHP on nephron formation, examined the programming of renal function and blood pressure and explored the mechanism in offspring. Maternal rats were treated with vehicle, 0.25 and 6.25mg/kg body weight/day DEHP respectively from gestation day 0 to postnatal day 21. Maternal DEHP exposure resulted in lower number of nephrons, higher glomerular volume and smaller Bowman's capsule in the DEHP-treated offspring at weaning, as well as glomerulosclerosis, interstitial fibrosis and effacement of podocyte foot processes in adulthood. In the DEHP-treated offspring, the renal function was lower and the blood pressure was higher. The renal protein expression of renin and angiotensin II was reduced at birth day and increased at weaning. Maternal DEHP exposure also led to reduced mRNA expression of some renal development involved genes at birth day, including Foxd1, Gdnf, Pax2 and Wnt11. While, the mRNA expression of some genes was raised, including Bmp4, Cdh11, Calm1 and Ywhab. These data show that maternal DEHP exposure impairs the offspring renal development, resulting in a nephron deficit, and subsequently elevated blood pressure later in life. Our findings suggest that DEHP exposure in developmental periods may affect the development of nephrons and adult renal disease through inhibition of the renin-angiotensin system.
Toxicology Letters 06/2012; 212(2):212-21. · 3.23 Impact Factor
-
Yi Lin,
Jie Wei,
Yuanyuan Li,
Jun Chen,
Zhao Zhou,
Liqiong Song,
Zhengzheng Wei,
Ziquan Lv,
Xi Chen,
Wei Xia,
Shunqing Xu
[show abstract]
[hide abstract]
ABSTRACT: -Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg(-1)·day(-1)) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes.
AJP Endocrinology and Metabolism 06/2011; 301(3):E527-38. · 4.75 Impact Factor
-
Jie Wei, Yi Lin,
Yuanyuan Li,
Chenjiang Ying,
Jun Chen,
Liqiong Song,
Zhao Zhou,
Ziquan Lv,
Wei Xia,
Xi Chen,
Shunqing Xu
[show abstract]
[hide abstract]
ABSTRACT: Bisphenol A (BPA), a widely used environmental endocrine disruptor, has been reported to disrupt glucose homeostasis. BPA exposure may be a risk factor for type 2 diabetes. In this study, we investigated the effects of early-life BPA exposure on metabolic syndrome in rat offspring fed a normal diet and a high-fat diet. Pregnant Wistar rats were exposed to BPA (50, 250, or 1250 μg/kg · d) or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a normal diet or a high-fat diet after weaning. Body weight, parameters of glucose and lipid metabolism, morphology, and function of β-cells were measured in offspring. On a normal diet, perinatal exposure to 50 μg/kg · d BPA resulted in increased body weight, elevated serum insulin, and impaired glucose tolerance in adult offspring. On a high-fat diet, such detrimental effects were accelerated and exacerbated. Furthermore, severe metabolic syndrome, including obesity, dyslipidemia, hyperleptindemia, hyperglycemia, hyperinsulinemia, and glucose intolerance, was observed in high-fat-fed offspring perinatally exposed to 50 μg/kg · d BPA. No adverse effect of perinatal BPA exposure at 250 and 1250 μg/kg · d was observed no matter on a normal diet or a high-fat diet. These results suggest that perinatal exposure to BPA at reference dose, but not at high dose, impairs glucose tolerance in adult rat offspring on a normal diet and predisposes offspring to metabolic syndrome at adult on a high-fat diet. High-fat diet intake is a trigger that initiates adverse metabolic effects of BPA.
Endocrinology 05/2011; 152(8):3049-61. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress has been considered as one of the possible mechanisms leading to the neurotoxicity of lead. One of the effective ways to prevent cellular damage after lead exposure is using antioxidants. In this paper, a novel C60-methionine derivate (FMD), a fullerene molecule modified with methionine, was synthesized. The protective effect of FMD on lead-exposed human SH-SY5Y neuroblastoma cells was investigated. In this research, after incubating with 500 µm Pb acetate alone for 72 h, the cells had undergone a series of biological changes including viability loss, apoptotic death, the depletion of glutathione (GSH), the peroxidation of membrane lipid and DNA damage. Pretreatment with FMD before lead exposure could improve cell survival, increase the GSH level, reduce malondialdehyde content and attenuate DNA damage without obvious toxicity. In addition, the protective effects of FMD were proven to be greater than those of other two C60-amino acid derivates, β-alanine C60 derivate and cystine C60 derivate, which have been confirmed in our previous work to be able to protect rat pheochromocytoma PC12 cells from hydrogen dioxide-induced oxidative injuries. These observations suggest that FMD may serve as a potential antioxidative and neuroprotective agent in the prevention of lead intoxication. Copyright © 2010 John Wiley & Sons, Ltd.
Journal of Applied Toxicology 03/2011; 31(3):255 - 261. · 2.48 Impact Factor
-
Huai-Cai Zeng,
Yuan-Yuan Li,
Ling Zhang,
Yan-Jian Wang,
Jun Chen,
Wei Xia, Yi Lin,
Jie Wei,
Zi-Quan Lv,
Miao Li,
Shun-Qing Xu
[show abstract]
[hide abstract]
ABSTRACT: Both animal and human studies have demonstrated that exposure to chemical pollutants during critical developmental period causes adverse consequences later in life. In uterus, perfluorooctanesulfonate (PFOS) exposure has been known to cause developmental neurotoxicity, such as increased motor activity, reduced habitation and impaired cognitive function. The possible mechanism of the impaired cognitive function induced by prenatal PFOS exposure was evaluated in this study. Pregnant Sprague Dawley (SD) rats were given 0.1, 0.6, and 2.0 mg kg(-1) birth weight (bw) d(-1) by gavage from gestation day (GD) 0 to GD20. Control received 0.5% Tween-20 vehicle (4 ml kg(-1) bw d(-1)). PFOS concentration in hippocampus of offspring was observed on postnatal day (PND) 0 and PND21. The ultrastructure of hippocampus and the gene expression of synaptic vesicle associated proteins in offspring hippocampus, which were important for the neurotransmitter release, were investigated. The transmission electron photomicrographs of the offspring hippocampus from PFOS-treated maternal groups showed the ultrastructure of synapses was negatively affected. The offspring from PFOS-treated maternal groups also differed significantly from controls with respect to the expression of synaptic vesicle associated proteins. The mRNA levels of synapsin1 (Syn1), synapsin2 (Syn2), and synaptophysin (Syp) were decreased in treated groups either on PND0 or on PND21. However, the mRNA level of synapsin3 (Syn3) decreased in 0.6- and 2.0-mg kg(-1) group on PND0, and showed no significant difference among control group and all treated groups on PND21. These results indicate that the impairment of cognitive function induced by PFOS may be attributed to the lower mRNA levels of synaptic vesicle associated proteins and the change of synaptic ultrastructure in hippocampus.
Synapse 03/2011; 65(3):225-33. · 2.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Numerous studies have indicated the neurotoxicity of perfluorooctane sulfonate (PFOS), a persistent and bioaccumulative compound, particularly during developmental stages of higher organisms. To explore the pro-inflammatory effect in the developmental neurotoxicity, effects of prenatal exposure to PFOS on glial activation in hippocampus and cortex were examined in offspring rats. Dams received 0.1, 0.6 and 2.0mg/kg bw PFOS by gavage from gestational day 2 (GD2) to GD21. Astrocyte activation markers, glial fibrillary acidic protein (GFAP) and S100 calcium binding protein B (S-100β) in hippocampus and cortex were both upregulated on postnatal day 0 (PND0) or PND21. In addition, the astrocyte activation was accompanied with the elevation of pro-inflammatory cytokines interleukin (IL-1β) and tumor necrosis factor (TNF)-α. The mRNA levels of pro-inflammatory transcription factors, including activation protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB) were also increased, at least in the 2.0mg/kg group. In addition to the inflammatory response, two synaptic proteins, synapsin 1 (Syn1) and synaptophysin (Syp) were reduced in cortex on PND0 and PND21. In hippocampus, the Syn1 were also reduced, while the Syp were increased in cortex on either PND0 or PND21. Obtained results indicated chronic glial activation with coexisting inflammatory and synapse injury features as a new mechanism of PFOS developmental neurotoxicity, and enhanced expression of AP-1, NF-κB and CREB may contributed to the adverse effect.
NeuroToxicology 10/2010; 32(1):130-9. · 3.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress has been considered as one of the possible mechanisms leading to the neurotoxicity of lead. One of the effective ways to prevent cellular damage after lead exposure is using antioxidants. In this paper, a novel C(60) -methionine derivate (FMD), a fullerene molecule modified with methionine, was synthesized. The protective effect of FMD on lead-exposed human SH-SY5Y neuroblastoma cells was investigated. In this research, after incubating with 500 µm Pb acetate alone for 72 h, the cells had undergone a series of biological changes including viability loss, apoptotic death, the depletion of glutathione (GSH), the peroxidation of membrane lipid and DNA damage. Pretreatment with FMD before lead exposure could improve cell survival, increase the GSH level, reduce malondialdehyde content and attenuate DNA damage without obvious toxicity. In addition, the protective effects of FMD were proven to be greater than those of other two C(60) -amino acid derivates, β-alanine C(60) derivate and cystine C(60) derivate, which have been confirmed in our previous work to be able to protect rat pheochromocytoma PC12 cells from hydrogen dioxide-induced oxidative injuries. These observations suggest that FMD may serve as a potential antioxidative and neuroprotective agent in the prevention of lead intoxication.
Journal of Applied Toxicology 09/2010; 31(3):255-61. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There is a growing demand for new technologies that are capable of screening the wide variety of xenoestrogens in environment. Here, a nanostructure electrochemical biosensor was developed to directly detect and screen estrogenic substances based on estrogen receptor (ER) binding without the use of radio- or enzyme-labeled compounds. The biosensor was fabricated by immobilization of ERs in supported bilayer lipid membrane (s-BLM) modified with Au nanoparticles, and the properties of the modified electrodes were characterized by cyclic voltammetry and impedance spectroscopy. The results indicated that the biosensor was able to detect the natural estrogen 17beta-estradiol with an acceptable linear correlation ranging from 5 to 150 ng/L and a detection limit of 1 ng/L. The biosensor could also detect other known xenoestrogens such as bisphenol A and 4-nonylphenol with satisfied sensitivity and quantitative results. The biosensor showed good reliability and repeatability, and the Au nanoparticles greatly enhanced the sensitivity and stability of the biosensor. Moreover, estrogenic activity of water samples determined by this biosensor was in good agreement with that determined by MCF-7 cell proliferation assay.
Biosensors & bioelectronics 03/2010; 25(10):2253-8. · 5.43 Impact Factor
-
Yan-jian Wan,
Yuan-yuan Li,
Wei Xia,
Jun Chen,
Zi-quan Lv,
Huai-cai Zeng,
Ling Zhang,
Wen-jie Yang,
Tian Chen, Yi Lin,
Jie Wei,
Shun-qing Xu
[show abstract]
[hide abstract]
ABSTRACT: The adverse environmental exposure in early life may have adverse effects on animals through epigenetic aspects. The current study examined the possibility of early epigenetic alteration in PFOS-exposed rat liver. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2 to 21. The dams were allowed to give birth and liver samples from weaned (postnatal day 21) offspring rats were analyzed for PFOS content, relative liver weight, global DNA methylation, methylation of LINE-1 regulatory region, tumor suppressor gene glutathione S-transferase pi (GSTP) and p16 promoter methylation level, as well as related genes expression level. In PFOS-exposed weaned rats, compared to the control, global DNA methylation and methylation of LINE-1 regulatory region decreased significantly only in the 2.0 mg/kg/d group. Up to 30% of critical CpG sites (+79, 81 and 84) in GSTP promoter region were methylated in the livers of PFOS-treated rats, while p16 promoter methylation was not affected. In addition, the up-regulated expression of GSTP was observed and this increase was associated with its main pathway of transcription regulation: Keap1-Nrf2/MafK. Thus, early-induced changes in critical cytosines within the GSTP gene promoter region may be a biomarker of hepatic PFOS burden, though their direct role in PFOS-induced hepatotoxicity, including its potential carcinogenic action, needs further research.
Toxicology 274(1-3):57-64. · 3.68 Impact Factor
