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Role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on ozone-exacerbated allergic asthma in mice
2019
Li, Jinquan | Chen, Yushan | Chen, Qiao Yi | Liu, Dan | Xu, Lang | Cheng, Guirong | Yang, Xu | Guo, Zhenzhong | Zeng, Yan
Around the globe, worsening air pollution is spawning major public health and environmental concerns, especially in the poorest and most populous cities. As a major secondary air pollutant, ozone is a potential risk factor for exacerbated asthma, although the underlying mechanisms remain uncertain. In this study, we aim to investigate the role of ozone on asthma exacerbation using a classic asthmatic model with allergic airway inflammation by treating Balb/c mice with ovalbumin (OVA). Our study shows ozone exposure significantly exacerbated OVA-induced asthmatic phenotypes, including serum immunoglobulin, Th cytokines, inflammatory cell counts, mucus production, airway remodeling, and airway hyper-responsiveness (AHR). Interestingly, expression of transient receptor potential cation channel subfamily V member1 (TRPV1) was also significantly elevated in ozone-exacerbated asthmatic mice and that treatment with TRPV1 antagonist effectively suppressed AHR, airway inflammation and remodeling. The underlying mechanisms of these effects may be associated with suppression of neuropeptide calcitonin gene-related peptide (CGRP) and thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine. Base on the role of TRPV1 in allergic asthma, this study further revealed that inhibition of TRPV1 by TRPV1 antagonist has significant anti-inflammatory effects on ozone-induced asthma exacerbation in this study. Induction of TRPV1 expression may be an important mechanism underlying the increased risks for asthma after exposure to environmental pollutants.
Afficher plus [+] Moins [-]Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring
2019
Ren, Xin | Dai, Pengyuan | Perveen, Aneela | Tang, Qian | Zhao, Liangyu | Qingyangwanxi, | Li, Yansen | Li, Chunmei
Glyphosate is the active ingredient in Roundup, one of the most popular herbicides in the world, and its toxicity has caused increasing concerns. The present study aims to investigate the toxic effects of prenatal exposure to pure glyphosate or Roundup on lipid metabolism in offspring. During gestational days (GDs), ICR mice (from Institute of Cancer Research) were given distilled water, 0.5% glyphosate solution (w/v, 0.5 g/100 ml) or 0.5%-glyphosate Roundup solution orally. The livers and serum samples of the offspring were collected on gestational day 19 (GD19), postnatal day 7 (PND7) and PND21. The results showed a significant decrease in the body weight and obvious hepatic steatosis with excessive lipid droplet formation in offspring. Moreover, the concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. Furthermore, there were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARα, which are related to lipid biosynthesis or catabolism in the liver. These results demonstrate that chronic prenatal exposure to glyphosate can result in lipid metabolism disruption in the offspring of mice, as glyphosate exerts a negative influence on the expression of lipogenesis genes.
Afficher plus [+] Moins [-]Perfluoroalkyl acids in paired serum, urine, and hair samples: Correlations with demographic factors and dietary habits
2019
Kim, Da-Hye | Lee, Jong Hyeon | Oh, Jeong-Eun
We analyzed paired serum, urine, and hair samples from 94 Korean children and adults to investigate levels of 11 perfluoroalkyl acids (PFAAs). The effects of demographic factors and dietary habits on PFAA exposure were also assessed based on the paired samples. The total PFAA concentrations were 2.4–31 ng/mL in serum, not detected–9.5 ng/mL in urine, and 0.48–15 ng/g in hair. Levels of perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), which have short carbon chains, were 1.5–5 fold higher in urine and hair than in serum. The PFAA concentrations in serum exhibited a decreasing trend with age from young childhood to adolescence, followed by an increasing trend after adolescence. For most PFAA species, concentrations in serum were higher in adult males than in adult females (p < 0.01). No sex difference was evident in the urine and hair samples. In addition, there was no age difference in the urine samples, but in the hair samples, we observed higher concentrations of PFAAs in children than in the other age groups (p < 0.01). The consumption rates of fish and water showed significant correlations with serum (positive correlation) and hair (negative) concentrations, respectively. No relationships between serum and hair/urine levels for most PFAAs were observed, except between serum and hair levels for perfluorooctanoic acid (PFOA).
Afficher plus [+] Moins [-]Di-(2-ethylhexyl) phthalate induced an increase in blood pressure via activation of ACE and inhibition of the bradykinin-NO pathway
2019
Deng, Ting | Xie, Xiaoman | Duan, Jiufei | Chen, Mingqing
Epidemiological studies and animal experiments have suggested that exposure to Di-(2-ethylhexyl) phthalate (DEHP) is strongly associated with an increase in blood pressure. However, the mechanisms that result in the detrimental effects of DEHP exposure on blood pressure are unclear. In our study, mice were orally exposed to DEHP dosages of 0.1, 1, 10 mg/kg/day for 6 weeks. The results showed that DEHP could induce a significant increase in systolic blood pressure (SBP) and heart rate, and a significant thickening of the ventricular wall. To explore the underlying mechanism, we measured the level of: angiotensin converting enzyme (ACE); bradykinin B2 receptor (BK2R); endothelial nitric oxide synthase (eNOS); bradykinin and Ca²⁺ in cardiac cytoplasm as well as in serum nitric oxide (NO). The results suggested that DEHP could induce an increase in ACE levels, and a decrease in bradykinin levels. Moreover, BK2R, Ca²⁺, eNOS and NO decreased when mice were exposed to 10 mg/kg/day DEHP. Interestingly, 5 mg/kg/day angiotensin converting enzyme inhibitor (ACEI) treatment inhibited the increase in blood pressure, and inhibited the decrease in the levels of BK2R, Ca²⁺, eNOS, and NO, that were induced by DEHP exposure. Our results suggest that DEHP might increase blood pressure by activating ACE expression, and inhibiting the bradykinin-NO pathway.
Afficher plus [+] Moins [-]Sex differences in the association between perfluoroalkyl acids and liver function in US adolescents: Analyses of NHANES 2013–2016
2019
Attanasio, Roberta
Perfluoroalkyl acids (PFAAs) are persistent in the environment, highly bio-accumulative in the body, and likely hepatotoxic in humans. There is evidence of sex-specific physiological responses to PFAA exposure. However, epidemiological studies seldom stratify the analyses by sex. Given the high prevalence of liver disease in general population adolescents, this study was designed to determine whether or not there is association between exposure to PFAAs and biomarkers of liver function in adolescent participants of the 2013–2016 National Health and Nutrition Examination Survey, and whether or not such association is sex-specific. Multivariate linear regressions were performed to examine the association between single PFAAs [perfluorooctane sulfonic acid (PFOS); linear form of perfluorooctanoic acid (PFOA); perfluorohexane sulfonic acid (PFHxS); perfluorononanoic acid (PFNA)], and biomarkers of liver function — gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin. Multivariate logistic regressions were performed to estimate adjusted odd ratios (aOR) of elevated ALT, AST and GGT. The study results show that, in females, there was a positive association of the highest PFOA quartile with increased ALT, AST and GGT, and the highest PFNA quartile with increased ALT and AST. Conversely, in male adolescents there was an association of the highest linear PFOA quartile with decreased ALT, and the highest PFNA quartile with ALT and AST. Females had higher odds of clinically-defined elevated ALT with increased PFOA (aOR = 1.79; 95% CI: 1.05, 3.04) or PFNA (aOR = 2.28; 95% CI: 1.08, 2.28), whereas males had decreased odds of clinically-defined elevated ALT with increased n-PFOA (aOR = 0.43; 95% CI: 0.20, 0.93) or PFNA (aOR = 0.5; 95% CI: 0.28, 0.89). In conclusion, there were sex differences in the association between serum PFAA levels and biomarkers of liver function. These results may provide support for analyzing sex-based adverse effects of PFAAs.
Afficher plus [+] Moins [-]Fluoride-induced unrestored arrest during haploid period of spermatogenesis via the regulation of DDX25 in rats
2019
Han, Yongli | Yu, Yuxiang | Liang, Zhen | Shi, Yan | Zhu, Yuchen | Zheng, Heping | Wang, Jundong | Zhang, Jianhai
The effect of fluoride as an ongoing topic has attracted much attentions due to the decline in overall human fertility worldwide. However, whether fluorine causes a temporary stimulus or permanent damage to the male reproductive system, as well as the mechanism of fluoride influencing spermatogenesis remained unclear. 48 adult male rats were randomly divided into four groups (twelve each). Control group received the distilled water, while the other three groups were treated with 25, 50, 100 mg/L NaF via drinking water for 8 weeks. Six rats from each group were selected randomly to detect the levels of various indices related to spermatogenesis. The remaining rats were given only distilled water and left for recovery of a period of 2 weeks. Results showed that the levels of serum CK, ALP, CHE, BUN, UA, and Cr, testis morphology and the ultrastructure of sperm acrosome and chromatoid body (CB) were significantly changed by fluoride. Interestingly, the elongated spermatid counts, spermatids elongation ratio, and mRNA expressions of Prm1/2 and MIWI, TDRD1, TDRD 6, TDRD7, PABP, and Hsp72 related to CB decreased markedly in fluoride treatment groups compared to the control. Furthermore, the expression levels of DDX25 and associated regulatory proteins like CRM1, HMG2, H4, TP2, and PGK2 were down-regulated by fluoride. After 2-weeks withdrawal period, out of the 19 altered spermatogenesis indicators, 15 indicators in 100 mg/L group and 3 indicators in 50 mg/L group still exhibited a significant change, while none showed change in 25 mg/L group. These results proved that the reversibility of fluoride toxicity is dose-dependent on the male reproductive system. Meanwhile, fluoride caused unrestored arrest during the haploid period of spermatogenesis, where reduced DDX25 and associated regulatory proteins play a crucial role in this process, which could provide the underlying insights to the toxic mechanism of fluoride induced male reproductive toxicity.
Afficher plus [+] Moins [-]Associations of ambient fine particulate matter and its constituents with serum complement C3 in a panel study of older adults in China
2019
Bai, Lu | Zhao, Meiduo | Xu, Jing | Li, Ang | Luo, Kai | Li, Runkui | Yang, Mingan | Xu, Qun
Epidemiological studies have demonstrated association between the total mass of fine particulate matter (PM2.5) exposures and inflammation. There are few studies exploring the associations between PM2.5 constituents and the biomarkers of inflammation in older adults and the underlying biological mechanisms are not exact. In this study, we examined the associations between PM2.5 and its constituents (organic carbon (OC), elemental carbon (EC), total carbon (TC), polycyclic aromatic hydrocarbons (PAHs) and complement three factor (C3), an important biomarker of inflammation in a repeated panel of 175 older adults in Beijing, China. We have constructed three different linear mixed effect models (single-pollutant model, constituent-PM2.5 joint model, and constituent-residual model) to evaluate the association of PM2.5 and its constituents and complement C3, controlling for concentration of high sensitive C-reactive protein (hs-CRP), day of week, mean temperature, relative humidity, location and potential individual confounders. We found robust positive associations of OC, EC, TC, PAHs and PM2.5 mass concentration with complement C3 at different lag patterns. The cumulative effects of pollutants increased across average of 2–5 days. Individuals aged 65 and above, or with diabetes, or BMI ≥30, or with no-cardiopathy, or with hypertension also exhibited positive associations between PM2.5 and complement C3. The results revealed that short-term exposure to PM2.5 and its constituents could result in a significant increase in serum level of complement C3. These findings suggested a possible involvement of complement C3 in the effect of PM2.5 on inflammatory reaction.
Afficher plus [+] Moins [-]Association between urinary thiodiglycolic acid level and hepatic function or fibrosis index in school-aged children living near a petrochemical complex
2019
Wang, Zhiwen | Liao, Kai-Wei | Chan, Chang-Chuan | Yu, Ming-Lung | Chuang, Hung-Yi | Chiang, Hung-Che | Huang, Po-Chin
The effect of exposure to vinyl chloride monomer (VCM) on susceptibility to hepatotoxicity in children is unknown, although experimental studies have demonstrated a significantly increased risk of hepatocellular carcinoma in rodents exposed to VCM in early life. Epidemiological studies have revealed a high prevalence of liver fibrosis and abnormal liver function in workers exposed to high VCM levels. We aimed to assess the association among urinary thiodiglycolic acid (TDGA) level, abnormal liver function, and hepatic fibrosis in school-aged children living near a petrochemical complex. A total of 303 school-aged (6–13 years) children within 10 km nearly a petrochemical complex was recruited in central Taiwan. First-morning urine and blood samples were collected from each subject, and urinary TDGA level was analyzed through liquid chromatography–tandem mass spectrometry. Liver function was determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hepatic fibrosis was assessed using the AST to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). Risk of hepatotoxicity induced by TDGA exposure was estimated using multivariate logistic regression. The median (range, subclinically abnormal %) AST and ALT levels of all subjects were 26.0 (17.0–99.0, 25.7%) and 15.0 (7.0–211.0, 5.9%) IU/L, respectively. Children in the highest urinary TDGA quartile (≥160.0 μg/g creatinine) exhibited significantly elevated median AST levels compared with those in the lowest quartiles (<35.4 μg/g creatinine, p = 0.033). After adjustment for potential confounding factors, children in the highest quartiles (Q₄) of TDGA level had significantly increased odds ratio (OR) of subclinically abnormal AST (OR = 3.86; 95% confidence interval: 1.54–9.67) compared with those in the lowest quartile. A dose-response trend (p = 0.004) was observed. Our findings support the hypothesis that elevated urinary TDGA level in children living near petrochemical complex is associated with susceptibility to hepatotoxicity.
Afficher plus [+] Moins [-]Association of serum levels of 4-tertiary-octylphenol with cardiovascular risk factors and carotid intima-media thickness in adolescents and young adults
2019
Lin, Chien-Yu | Hwang, Yi-Ting | Chen, Pau-Chung | Sung, Fung-Chang | Su, Ta-Chen
In the family of alkylphenolic compounds, 4-tertiary-Octylphenol (4-t-OP) is extensively used in many products. In animal and in vitro studies, 4-t-OP exposure has been linked to cardiovascular disease (CVD) risk factors; however, there are no previous human epidemiological studies. In this study, 886 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between serum levels of 4-t-OP, CVD risk factors, and common carotid artery intima-media thickness (CIMT). The geometric mean (SD) 4-t-OP concentration was 32.52 (1.71) ng/mL. We found that serum levels of 4-t-OP were negatively associated with markers of glucose homeostasis (insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β)), z score of body mass index (BMI z score) and CIMT but were positively associated with lipid profiles (high density lipoprotein cholesterol (HDL-C), Apolipoprotein A1). A one-unit elevation in natural log-transformed 4-t-OP (ng/mL) was negatively correlated with CIMT (mm) (β = −0.029, SE = 0.003, P < 0.001) in multiple linear regression analyses. The relationship between 4-t-OP and CIMT remained the same in all subgroups or if bisphenol A (BPA) was considered a covariate. In this study, we observed that higher levels of 4-t-OP levels were negatively correlated with markers of glucose homeostasis, BMI z score, and CIMT; positively correlated with lipid profiles (HDL-C and apolipoprotein A) in this cohort. Future research on exposure to 4-t-OP and CVD risk factors is warranted.
Afficher plus [+] Moins [-]Exposure to Aroclor 1254 persistently suppresses the functions of pancreatic β-cells and deteriorates glucose homeostasis in male mice
2019
Xi, Zhihui | Fang, Lu | Xu, Jing | Li, Bingshui | Zuo, Zhenghong | Lv, Liangju | Wang, Chonggang
Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have been shown to be related to the occurrence of type 2 diabetes mellitus (T2DM). Nevertheless, it is necessary to further explore the development of T2DM caused by PCBs and its underlying mechanisms. In the present study, 21-day-old C57BL/6 male mice were orally treated with Aroclor 1254 (0.5, 5, 50 or 500 μg kg−1) once every three days. After exposure for 66 d, the mice showed impaired glucose tolerance, 13% and 14% increased fasting serum insulin levels (FSIL), and 63% and 69% increases of the pancreatic β-cell mass in the 50 and 500 μg kg−1 groups, respectively. After stopping exposure for 90 d, treated mice returned to normoglycemia and normal FSIL. After re-exposure of these recovered mice to Aroclor 1254 for 30 d, fasting plasma glucose showed 15%, 28% and 16% increase in the 5, 50 and 500 μg kg−1 treatments, FSIL exhibited 35%, 27%, 30% and 32% decrease in the 0.5, 5, 50 or 500 μg kg−1 groups respectively, and there was no change in pancreatic β-cell mass. Transcription of the pancreatic insulin gene (Ins2) was significantly down-regulated in the 50 and 500 μg kg−1 groups, while DNA-methylation levels were simultaneously increased in the Ins2 promoter during the course of exposure, recovery and re-exposure. Reduced insulin levels were initially rescued by a compensative increase in β-cell mass. However, β-cell mass eventually failed to make sufficient levels of insulin, resulting in significant increases in fasting blood glucose, and indicating the development of T2DM.
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