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Exposure to 2,3,3′,4,4′,5-hexachlorobiphenyl promotes nonalcoholic fatty liver disease development in C57BL/6 mice
2020
Shan, Qiuli | Chen, Ningning | Liu, Wei | Qu, Fan | Chen, Anhui
Previous in vitro studies have indicated that 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB 156) may be a new contributor to metabolic disruption and may further cause the occurrence of nonalcoholic fatty liver disease (NAFLD). However, no study has clarified the specific contributions of PCB 156 to NAFLD progression by constructing an in vivo model. Herein, we evaluated the effects of PCB 156 treatment (55 mg/kg, i.p.) on the livers of C57BL/6 mice fed a control diet (CD) or a high-fat diet (HFD). The results showed that PCB 156 administration increased intra-abdominal fat mass, hepatic lipid levels and dyslipidemia in the CD-fed group and aggravated NAFLD in HFD-fed group. By using transcriptomics studies and biological methods, we found that the genes expression involved in lipid metabolism pathways, such as lipogenesis, lipid accumulation and lipid β-oxidation, was greatly altered in liver tissues exposed to PCB 156. In addition, the cytochrome P450 pathway, peroxisome proliferator-activated receptors (PPARs) and the glutathione metabolism pathway were significantly activated following exposure to PCB 156. Furthermore, PCB 156 exposure increased serum transaminase levels and lipid peroxidation, and the redox-related genes were significantly dysregulated in liver tissue. In conclusion, our data suggested that PCB 156 could promote NAFLD development by altering the expression of genes related to lipid metabolism and inducing oxidative stress.
اظهر المزيد [+] اقل [-]Alternatives of perfluoroalkyl acids and hepatitis B virus surface antibody in adults: Isomers of C8 Health Project in China
2020
Zeng, Xiao-Wen | Li, Qing-Qing | Chu, Chu | Ye, Wan-Lin | Yu, Shu | Ma, Huimin | Zeng, Xiao-Yun | Zhou, Yang | Yu, Hong-Yao | Hu, Liwen | Yang, Bo-Yi | Dong, Guang-Hui
Previous epidemiological and experimental studies have shown that legacy perfluoroalkyl acids (PFAAs) are immunotoxic. However, whether the immunosuppressive effects in PFAA alternatives which recently have been widely detected in the environment are unknown. To address this knowledge gap, we investigated the relationship of serum legacy PFAAs and PFAA alternatives with the antibody of hepatitis B virus in adults. We recruited 605 participants from a cross-sectional study, the Isomer of C8 Health Project in China. We measured two representative legacy PFAAs (perfluorooctane sulfonate, PFOS and perfluorooctanoic acid, PFOA), and three PFAA alternatives (two chlorinated polyfluorinated ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) in serum using ultra-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS). We applied linear and logistic regression models to analyze associations between serum PFAAs and hepatitis B surface antibody (HBsAb) with multivariable adjustments. We found negative associations between serum PFAAs concentrations and HBsAb. Lower serum HBsAb levels (log mIU/mL) were observed for each log-unit increase in linear PFOS (β = −0.31, 95% confidential interval: 0.84, −0.18), 6:2 PFESA (β = −0.81, 95% CI: 1.20, −0.42), 8:2 PFESA (β = −0.29, 95% CI: 0.43, −0.14) and PFBA (β = −0.18, 95% CI: 0.28, −0.08). The association between PFAAs and HBsAb seronegative seemed to be higher for 6:2 PFESA (odds ratio = 3.32, 95% CI: 2.16, 5.10) than its predecessors, linear PFOS (OR = 1.96, 95% CI: 1.37, 2.81) and branched PFOS isomers (OR = 1.64, 95% CI: 1.05, 2.56). We report new evidence that exposure to PFAA alternatives are associated with lower HBsAb in adults. This association seems to be stronger in 6:2 PFESA than PFOS. Our results suggest that more studies are needed to clarify the potential toxicity of PFAA alternatives in human which will facilitate better chemical regulations for PFAAs.
اظهر المزيد [+] اقل [-]Human exposure to PBDEs in e-waste areas: A review
2020
Polybrominated biphenyl ethers (PBDEs) are commonly added to electronic products for flame-retardation effects, and are attracting more and more attentions due to their potential toxicity, durability and bioaccumulation. This study conducts a sysmtematic review to understand the human exposure to PBDEs from e-waste recycling, especially exploring the exposure pathways and human burden of PBDEs as well as investigating the temporal trend of PBDEs exposure worldwide. The results show that the particular foods (contaminated fish, poultry, meat and breast milk) ingestion, indoor dust ingestion and indoor air inhalation may be key factors leading to human health risks of PBDEs exposure in e-waste recycling regions. Residents and some vulnerable groups (occupational workers and children) in e-waste recycling areas may face higher exposure levels and health risks. PBDE exposure is closely related to exposure level, exposure duration, e-waste recycling methods, and dietary customs. High levels of PBDEs are found in human tissues (breast milk, hair, blood (serum), placenta and other tissues) in e-waste areas, at far higher levels than in other areas. Existing data indicate that PBDE exposure levels do not present any apparent downward trend, and will possibly cause serious human diseases. More epidemiological studies are still needed to provide a solid basis for health risk assessment.
اظهر المزيد [+] اقل [-]The endoplasmic reticulum stress and related signal pathway mediated the glyphosate-induced testosterone synthesis inhibition in TM3 cells
2020
Xia, Yongpeng | Yang, Xiaobo | Lu, Jingchun | Xie, Qixin | Ye, Anfang | Sun, Wenjun
Glyphosate is the most widely used herbicide in the world. In recent years, many studies have demonstrated that exposure to glyphosate-based herbicides (GHBs) was related to the decrease of serum testosterone and the decline in semen quality. However, the molecular mechanism of glyphosate-induced testosterone synthesis disorders is still unclear. In the present study, the effects of glyphosate on testosterone secretion and the role of endoplasmic reticulum (ER) stress in the process were investigated in TM3 cells. The effects of glyphosate at different concentrations on the viability of TM3 cells were detected by CCK8 method. The effect of glyphosate exposure on testosterone secretion was determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of testosterone synthases and ER stress-related proteins were detected by Western blot and Immunofluorescence stain. Results showed that exposure to glyphosate at concentrations below 200 mg/L had no effect on cell viability, while the glyphosate above 0.5 mg/L could inhibit the testosterone secretion in TM3 cells. Treatment TM3 cells with glyphosate at 5 mg/L not only reduced the protein levels of testosterone synthase StAR and CYP17A1, inhibited testosterone secretion, but also increased the protein level of ER stress molecule Bip and promoted the phosphorylation of PERK and eIF2α. Pretreatment cells with PBA, an inhibitor of ER stress, alleviated glyphosate-induced increase in Bip, p-PERK and p-eIF2α protein levels, meanwhile rescuing glyphosate-induced testosterone synthesis disorders. When pretreatment with GSK2606414, a PERK inhibitor, the glyphosate-induced phosphorylation of PERK and eIF2α was blocked, and the glyphosate-inhibited testosterone synthesis and secretion was also restored. Overall, our findings suggest that glyphosate can interfere with the expression of StAR and CYP17A1 and inhibit testosterone synthesis and secretion via ER stress-mediated the activation of PERK/eIF2α signaling pathway in Leydig cells.
اظهر المزيد [+] اقل [-]High and low temperatures aggravate airway inflammation of asthma: Evidence in a mouse model
2020
Deng, Linjing | Ma, Ping | Wu, Yang | Ma, Yongsheng | Yang, Xu | Li, Yuguo | Deng, Qihong
Epidemiology suggests ambient temperature is the triggers and potential activator of asthma. The role of high and low temperatures on airway inflammation of asthma, and the underlying molecular mechanism are not yet understood. A mouse model of asthma was adopted in our experiment. The BALB/c mice were exposed at different temperature for 4 h (2 h in the morning and 2 h in the afternoon) on weekday. The exposure temperatures were 10 °C, 24 °C and 40 °C. Ovalbumin (OVA) was used to sensitize the mice on days 14, 18, 22, 26, and 30, followed by an aerosol challenge for 30 min from day 32–38. After the final OVA challenge, lung function, serum protein and pulmonary inflammation were assessed. Comparing the OVA with the saline group at 24 °C, we saw a significant increase in: serum Total-IgE (p < 0.05); OVA-sIgE (p < 0.01); IL-4 (p < 0.05); IL-1β (p < 0.01); IL-6 (p < 0.01); TNF-α (p < 0.01); and the ratio of IL-4/IFN-γ (p < 0.01). At the same time, there was a significant decrease in IFN-γ (p < 0.01). As the temperature increase, there is a U shape for immune proteins and pro-inflammatory factors with a peak value at 24 °C, exception for IFN-γ (inverted U-shape). After the high and low temperature exposure, the Ri and Re increased significantly, while Cldyn decreased significantly compared with the 24 °C group. Histopathological analysis of the OVA groups showed airway remodeling, airway wall thickening and deforming, and subepithelial fibrosis. More obvious changes were found in the high and low temperature exposure groups. The immunohistochemistry suggested that TRPs changed with temperatures. High and low temperatures can aggravate airway inflammation in a mouse model of asthma. TRPs play an important role in temperature aggravation of allergic asthma. The results suggest that asthmatics should avoid exposure to high and low temperatures for too long time.
اظهر المزيد [+] اقل [-]Is dietary macronutrient intake associated with serum concentrations of organochlorine pesticides in humans?
2020
Lee, Yu-Mi | Heo, Somi | Kim, Se-A | Lee, Duk-Hee
In the general population, chronic exposure to low-dose persistent organic pollutants (POPs), particularly organochlorine pesticides (OCPs), has been recently linked to many chronic diseases. Widespread contamination of the food chain and human adipose tissue has made avoiding exposure to these chemicals impossible; thus, alternative strategies for decreasing the chemical burden must be investigated. Recently, macronutrient intake was found to significantly modify the toxicokinetics of POPs in animal experimental studies. Thus, we evaluated whether macronutrient intake was related to serum concentrations of OCPs in healthy adults without cardio-metabolic diseases. Subjects included 1,764 adults, aged 20 years or above, who participated in the National Health and Nutrition Examination Survey 1999–2004. Macronutrient intake was assessed based on a 24-h dietary recall interview. Six individual OCPs commonly detected among the general population were evaluated as markers of OCPs and other coexisting lipophilic chemicals stored in adipose tissue and released into circulation. High fat intake was associated with lower concentrations of OCPs, while high carbohydrate intake showed the opposite result. When three types of fats were individually evaluated, both saturated fatty acids and monounsaturated fatty acids, but not polyunsaturated fatty acids, were inversely associated with serum concentrations of OCPs. Adjustment for possible confounders did not change the results. When stratified by age, gender, body mass index, and physical activity, these associations were similar in most subgroups. Thus, similar to the findings observed in animal experimental studies, a moderate-fat diet with low carbohydrate intake was related to low serum concentrations of OCPs in humans. Although these findings need to be replicated, changing dietary macronutrient intake can be investigated as a practical strategy for dealing with unavoidable lipophilic chemical mixtures such as OCPs in modern society.
اظهر المزيد [+] اقل [-]Ambient PM2.5 exposures and systemic biomarkers of lipid peroxidation and total antioxidant capacity in early pregnancy
2020
Zhang, Yujuan | Wang, Jianmei | Gong, Xian | Chen, Li | Zhang, Bumei | Wang, Qina | Han, Bin | Zhang, Nan | Xue, Fengxia | Vedal, Sverre | Bai, Zhipeng
Evidence for effects of PM₂.₅ on systemic oxidative stress in pregnant women is limited, especially in early pregnancy. To estimate the associations between ambient PM₂.₅ exposures and biomarkers of lipid peroxidation and total antioxidant capacity (T-AOC) in women with normal early pregnancy (NEP) and women with clinically recognized early pregnancy loss (CREPL), 206 early pregnant women who had measurements of serum malondialdehyde (MDA) and T-AOC were recruited from a larger case-control study in Tianjin, China from December 2017 to July 2018. Ambient PM₂.₅ concentrations of eight single-day lags exposure time windows before blood collection at the women’s residential addresses were estimated using temporally-adjusted land use regression models. Effects of PM₂.₅ exposures on percentage change in the biomarkers were estimated using multivariable linear regression models adjusted for month, temperature, relative humidity, gestational age and other covariates. Unconstrained distributed lag models were used to estimate net cumulative effects. Increased serum MDA and T-AOC were significantly associated with increases in PM₂.₅ at several lag exposure time windows in both groups. The net effects of each interquartile range increase in PM₂.₅ over the preceding 8 days on MDA were significantly higher (p < 0.001) in CREPL [52% (95% CI: 41%, 62%)] than NEP [22% (95% CI: 9%, 36%)] women. Net effects of each interquartile range increase in PM₂.₅ over the preceding 5 days on T-AOC were significantly lower (p = 0.010) in CREPL [14% (95% CI: 9%, 19%)] than NEP [24% (95% CI: 18%, 29%)] women. Exposure to ambient PM₂.₅ may induce systemic lipid peroxidation and antioxidant response in early pregnant women. More severe lipid peroxidation and insufficient antioxidant capacity associated with PM₂.₅ was found in CREPL women than NEP women. Future studies should focus on mechanisms of individual susceptibility and interventions to reduce PM₂.₅-related oxidative stress in the first trimester.
اظهر المزيد [+] اقل [-]Maternal exposure to ambient air pollution during pregnancy and lipid profile in umbilical cord blood samples; a cross-sectional study
2020
Heydari, Hafez | Abroudi, Mina | Adli, Abolfazl | Pirooznia, Nazanin | Najafi, Moslem Lari | Pajohanfar, Nasim Sadat | Dadvand, Payam | Miri, Mohammad
Adverse health effects of exposure to air pollution have been investigated in many previous studies. However, there is no study available on the association between maternal exposure to air pollution during pregnancy and cord blood lipid profile. This study, based on 150 mother-newborn pairs residing in Sabzevar, Iran (2018), evaluated the association of exposure to ambient air pollution as well as traffic indicators (total street length in different buffers around residential address and distance to major roads) during entire pregnancy with lipid levels cord blood lipid profile. Concentrations of PM₁₀, PM₂.₅, and PM₁ at maternal residential address were estimated using land use regression (LUR) models. We measured triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) levels and TC/HDL-C and TAG/HDL-C ratio in the cord blood samples to characterize their lipid profile. Multiple linear regression models were developed to estimate the association of exposure to air pollution and traffic indicators with cord blood lipid profile controlled for relevant covariates. Higher concentrations of PM₂.₅ and PM₁₀ were associated with higher levels of TAG, TC, HDL-C, TC/HDL-C, and TAG/HDL-C in cord blood samples. Moreover, higher concentration of PM₁ was associated with higher levels of TAG, TC and LDL-C. There was also a positive association between total street length in 100 m buffer around home and serum levels of TC, TAG, LDL-C and TC/HDL ratio (β = 3.73, 95% confidence intervals (CI): 1.76, 5.71; β = 2.75, 95% CI: 0.97, 4.53; β = 1.87, 95% CI: 0.64, 3.09; β = 0.06, 95% CI: 0.01, 0.11, respectively). However, the associations for total street length in larger buffers and distance to major roads were not statistically significant. Our findings support a relationship between exposure to air pollution during pregnancy and increase in cord blood lipid levels.
اظهر المزيد [+] اقل [-]Characterization of pharmaceuticals, personal care products, and polybrominated diphenyl ethers in lake sturgeon serum and gametes
2020
Banda, Jo A. | Gefell, Dan | An, Viktoriya | Bellamy, Amber | Biesinger, Zy | Boase, James | Chiotti, Justin | Gorsky, Dimitry | Robinson, Timothy | Schlueter, Scott | Withers, Jonah | Hummel, Stephanie L.
Recent research suggests contaminants of emerging concern (CECs) are widespread and environmentally relevant concentrations can impact fishes. However, little is known about impacts of CECs to long-lived or rare species. The objective of this study was to characterize CEC concentrations in lake sturgeon (Acipenser fulvescens) serum and gametes. Blood serum was collected non-lethally from lake sturgeon at four lower Great Lakes basin sites: Detroit, upper Niagara, lower Niagara, and St. Lawrence rivers; additionally, gametes were collected from lake sturgeon in the St. Lawrence River. Samples were analyzed for pharmaceuticals and personal care products (PPCPs) and polybrominated diphenyl ethers (PBDEs). Overall, 44 different PPCPs were identified in serum and gamete samples across sites, with 22 PPCPs identified in at least 25% of serum samples and three PPCPs identified in 25% of gamete samples. PPCP concentrations in serum and gametes ranged from 0.00208 to 130 ppb and 0.00538–190 ppb, respectively. NMDS ordination revealed differences in the presence and concentrations of PPCPs in lake sturgeon serum across sites, however, N,N-diethyl-meta-toluamide (DEET), hydrocortisone, benztropine, and amitriptyline were detected in at least one serum sample at all sites. Additionally, DEET, 10-hydroxy-amitriptyline, and sertraline were detected in ≥25% of gamete samples collected from the St. Lawrence River. Twenty-six PBDE congeners were identified in 25% of serum samples and 24 were identified in 25% of gamete samples. PBDEs in serum were present across all sites and in gametes of St. Lawrence River lake sturgeon, and total PBDE concentrations in serum and gametes ranged from 0.184 to 12.7 ppb and 0.0826–0.44 ppb, respectively. Managers of lake sturgeon populations may need to consider the impacts of CECs if reproductive, developmental, behavioral, growth effects, or mortality are observed in the Great Lakes basin or other areas that are impacted by increased exposures to PPCPs and PBDEs.
اظهر المزيد [+] اقل [-]Maternal prenatal urinary bisphenol A level and child cardio-metabolic risk factors: A prospective cohort study
2020
Ouyang, Fengxiu | Zhang, Guang-Hui | Du, Kun | Shen, Lixiao | Ma, Rui | Wang, Xia | Wang, Xiaobin | Zhang, Jun
Exposure to endocrine disrupting chemicals during the first 1000 days of life may have long-lasting adverse effects on cardio-metabolic risk in later life. This study aimed to examine the associations between maternal prenatal Bisphenol A (BPA) exposure and child cardio-metabolic risk factors at age 2 years in a prospective cohort. During 2012–2013, 218 pregnant women were enrolled at late pregnancy from Shanghai, China. Urinary BPA concentration was measured in prenatal and child 2-year spot urine samples, and classified into high, medium and low tertiles. Child adiposity anthropometric measurements, random morning plasma glucose, serum insulin, and lipids (high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride), systolic (SBP) and diastolic blood pressure (DBP) were measured. Linear regression was used to evaluate the associations between prenatal BPA and each of the cardio-metabolic risk factors in boys and girls, respectively, adjusting for pertinent prenatal, perinatal and postnatal factors. BPA was detectable (>0.1 μg/L) in 98.2% of mothers prenatally and 99.4% of children at age 2 years. Compared to those with low prenatal BPA, mean SBP was 7.0 (95%CI: 2.9–11.2) mmHg higher, and DBP was 4.4 (95%CI: 1.2–7.5) mmHg higher in girls with high prenatal BPA levels, but these associations were not found in boys. In boys, medium maternal prenatal BPA level was associated with 0.36 (95% CI: 0.04–0.68) mmol/L higher plasma glucose. No associations were found between prenatal BPA and child BMI, skinfold thicknesses, serum lipids, or insulin in either girls or boys. There were no associations between concurrent child urinary BPA and cardio-metabolic risk factors. These results support that BPA exposure during prenatal period, susceptible time for fetal development, may be associated with increase in child BP and plasma glucose in a sex-specific manner. Further independent cohort studies are needed to confirm the findings.
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