Refine search
Results 1-10 of 13
Di-(2-ethylhexyl) phthalate enhances melanoma tumor growth via differential effect on M1-and M2-polarized macrophages in mouse model
2018
Yi, Chae-uk | Park, Sojin | Han, Hae-Kyoung | Gye, Myung Chan | Moon, Eun-Yi
Phthalates are widely used as plasticizers that influence sexual and reproductive development. Here, we investigated whether di-(2-ethylhexyl) phthalate (DEHP) affects macrophage polarization that are associated with tumor initiation and progression. No changes were observed in LPS- or ConA-stimulated in vitro spleen B or T cell proliferation for 48 h, respectively. In contrast, macrophage functions were inhibited in response to DEHP for 12 h as judged by LPS-induced H₂O₂ and NO production and zymosan A-mediated phagocytosis. When six weeks old male mice were pre-exposed to 4.0 mg/kg DEHP for 21 days before the injection of B16F10 melanoma cells and post-exposed to 4.0 mg/kg DEHP for 7 days, tumor nodule formation and the changes in tumor volume were higher than those in control group. Furthermore, when male mice were intraperitoneally pretreated with DEHP for 3 or 4 weeks and peritoneal exudate cells (PECs) or bone marrow-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), the expression of COX-2, TNF-α, and IL-6 was reduced in DEHP-pretreated cells as compared with that in LPS-stimulated control cells. While the production of nitric oxide (NO) for 18 h was reduced by LPS-stimulated PECs and M1-type BMDMs, IL-4 expression was enhanced in LPS-stimulated BMDMs. When BMDMs were incubated with IL-4 for 30 h, arginase 1 for M2-type macrophages was increased in transcriptional and translational level. Data implicate that macrophages were differentially polarized by DEHP treatment, which reduced M1-polarzation but enhanced M2-polarization. Taken together, these data demonstrate that DEHP could affect in vivo immune responses of macrophages, leading to the suppression of their tumor-preventing ability. This suggests that individuals at high risk for tumor incidence should avoid long-term exposure to various kind of phthalate including DEHP.
Show more [+] Less [-]Dioxin-like PCB 126 increases intestinal inflammation and disrupts gut microbiota and metabolic homeostasis
2018
Petriello, Michael C. | Hoffman, Jessie B. | Vsevolozhskaya, Olga | Morris, Andrew J. | Hennig, Bernhard
The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of host metabolism. Additionally, gut inflammation is an independent risk factor for the development of metabolic diseases, specifically atherosclerosis and diabetes. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing cardiometabolic diseases. We aimed to elucidate the detrimental impacts of dioxin-like pollutant exposure on gut microbiota and host gut health and metabolism in a mouse model of cardiometabolic disease. We utilized 16S rRNA sequencing, metabolomics, and regression modeling to examine the impact of PCB 126 on the microbiome and host metabolism and gut health. 16S rRNA sequencing showed that gut microbiota populations shifted at the phylum and genus levels in ways that mimic observations seen in chronic inflammatory diseases. PCB 126 reduced cecum alpha diversity (0.60 fold change; p = 0.001) and significantly increased the Firmicutes to Bacteroidetes ratio (1.63 fold change; p = 0.044). Toxicant exposed mice exhibited quantifiable concentrations of PCB 126 in the colon, upregulation of Cyp1a1 gene expression, and increased markers of intestinal inflammation. Also, a significant correlation between circulating Glucagon-like peptide-1 (GLP-1) and Bifidobacterium was evident and dependent on toxicant exposure. PCB 126 exposure disrupted the gut microbiota and host metabolism and increased intestinal and systemic inflammation. These data imply that the deleterious effects of dioxin-like pollutants may be initiated in the gut, and the modulation of gut microbiota may be a sensitive marker of pollutant exposures.
Show more [+] Less [-]COPD rat model is more susceptible to cold stress and PM2.5 exposure and the underlying mechanism
2018
Zhang, Kai | Guo, Lei | Wei, Qiaozhen | Song, Quanquan | Liu, Jiangtao | Niu, Jingping | Zhang, Li | Ruan, Ye | Luo, Bin
The purpose of this study is to verify the hypothesis that chronic obstructive pulmonary disease (COPD) model rat is more susceptible to cold stress and fine particulate matter (PM2.5) exposure than the healthy rat, and explore the related mechanism. COPD rat model, established with cigarette smoke and lipopolysaccharide intratracheal instillation, were exposed to cold stress (0 °C) and PM2.5 (0, 3.2, 12.8 mg/ml). After that, the levels of superoxide dismutase, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and angiotensin Ⅱ (Ang-Ⅱ) in lung were measured, as well as the expression levels of lung 8-hydroxy-2-deoxyguanosine (8-OHdG), nuclear factor kappa B (NF-κB), heme-oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2). There were significant positive relationships between PM2.5 and lung level of iNOS, TNF-α, MCP-1 and Ang-Ⅱ, lung function and pathologic damage in COPD rats. The HO-1, NF-κB and 8-OHdG were found highly expressed in COPD rat lung, particularly at the higher PM2.5 dose of cold stress groups, while Nrf2 was found declined. Thus, COPD rats may be more susceptible to cold stress and PM2.5 exposure. Cold stress may aggravate PM2.5-induced toxic effects in the lung of COPD rats through increasing Ang-Ⅱ/NF-κB signaling pathway and suppressing Nrf2 signaling pathway.
Show more [+] Less [-]Can in vitro assays account for interactions between inorganic co-contaminants observed during in vivo relative bioavailability assessment?
2018
Ollson, Cameron J. | Smith, Euan | Juhasz, Albert L.
In vitro assays act as surrogate measurements of relative bioavailability (RBA) for inorganic contaminants. The values derived from these assays are routinely used to refine human health risk assessments (HHRA). Extensive in vitro research has been performed on three major inorganic contaminants; As, Cd and Pb. However, the majority of these studies have evaluated the contaminants individually, even in cases when they are found as co-contaminants. Recently, in vivo studies (animal model) have determined that when the three aforementioned contaminants are present in the same soil matrix, they have the ability to influence each other's individual bioavailability. Since in vitro assays are used to inform HHRA, this study investigated whether bioaccessibility methods including the Solubility/Bioavailability Research Consortium (SBRC) assay, and physiologically based extraction test (PBET), have the ability to detect interactions between As, Cd and Pb. Using a similar dosing methodology to recently published in vivo studies, spiked aged (12 years) soil was assessed by evaluating contaminant bioaccessibility individually, in addition to tertiary combinations. In two spiked aged soils (grey and brown chromosols), there was no influence on contaminant bioaccessibility when As, Cd and Pb we present as co-contaminants. However, in a red ferrosol, the presence of As and Pb significantly decreased (p < 0.05) the bioaccessibility of Cd when assessed using gastric and intestinal phases of the SBRC assay and the PBET. Conceivable, differences in key physico-chemical properties (TOC, Fe, Al, P) between the study soils influenced contaminant interactions and bioaccessibility outcomes. Although bioaccessibility methods may not account for interactions between elements as demonstrated in in vivo models, in vitro assessment provides a conservative prediction of contaminant RBA under co-contaminant scenarios.
Show more [+] Less [-]Inhalational exposure to particulate matter air pollution alters the composition of the gut microbiome
2018
Mutlu, Ece A. | Comba, Işın Y. | Cho, Takugo | Engen, Phillip A. | Yazıcı, Cemal | Soberanes, Saul | Hamanaka, Robert B. | Niğdelioğlu, Recep | Meliton, Angelo Y. | Ghio, Andrew J. | Budinger, G.R Scott | Mutlu, Gökhan M.
Recent studies suggest an association between particulate matter (PM) air pollution and gastrointestinal (GI) disease. In addition to direct deposition, PM can be indirectly deposited in oropharynx via mucociliary clearance and upon swallowing of saliva and mucus. Within the GI tract, PM may alter the GI epithelium and gut microbiome. Our goal was to determine the effect of PM on gut microbiota in a murine model of PM exposure via inhalation. C57BL/6 mice were exposed via inhalation to either concentrated ambient particles or filtered air for 8-h per day, 5-days a week, for a total of 3-weeks. At exposure's end, GI tract tissues and feces were harvested, and gut microbiota was analyzed. Alpha-diversity was modestly altered with increased richness in PM-exposed mice compared to air-exposed mice in some parts of the GI tract. Most importantly, PM-induced alterations in the microbiota were very apparent in beta-diversity comparisons throughout the GI tract and appeared to increase from the proximal to distal parts. Changes in some genera suggest that distinct bacteria may have the capacity to bloom with PM exposure. Exposure to PM alters the microbiota throughout the GI tract which maybe a potential mechanism that explains PM induced inflammation in the GI tract.
Show more [+] Less [-]Predicting the effects of polychlorinated biphenyls on cetacean populations through impacts on immunity and calf survival
2018
Hall, Ailsa J. | McConnell, Bernie J. | Schwacke, Lori H. | Ylitalo, Gina M. | Williams, Rob | Rowles, Teri K.
The potential impact of exposure to polychlorinated biphenyls (PCBs) on the health and survival of cetaceans continues to be an issue for conservation and management, yet few quantitative approaches for estimating population level effects have been developed. An individual based model (IBM) for assessing effects on both calf survival and immunity was developed and tested. Three case study species (bottlenose dolphin, humpback whale and killer whale) in four populations were taken as examples and the impact of varying levels of PCB uptake on achievable population growth was assessed. The unique aspect of the model is its ability to evaluate likely effects of immunosuppression in addition to calf survival, enabling consequences of PCB exposure on immune function on all age-classes to be explored. By incorporating quantitative tissue concentration-response functions from laboratory animal model species into an IBM framework, population trajectories were generated. Model outputs included estimated concentrations of PCBs in the blubber of females by age, which were then compared to published empirical data. Achievable population growth rates were more affected by the inclusion of effects of PCBs on immunity than on calf survival, but the magnitude depended on the virulence of any subsequent encounter with a pathogen and the proportion of the population exposed. Since the starting population parameters were from historic studies, which may already be impacted by PCBs, the results should be interpreted on a relative rather than an absolute basis. The framework will assist in providing quantitative risk assessments for populations of concern.
Show more [+] Less [-]Concentrations of selected heavy metals in placental tissues and risk for neonatal orofacial clefts
2018
Pi, Xin | Qiao, Yiran | Wei, Yihui | Jin, Lei | Li, Zhiwen | Liu, Jufen | Zhang, Yali | Wang, Linlin | Liu, Yaqiong | Xie, Qing | Ren, Aiguo
Orofacial clefts (OFCs) have multifactorial etiologies. Prenatal exposure to heavy metals can induce OFCs in animal models, but evidence from studies of human subjects is scarce. We examined whether concentrations of mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) in placental tissues are associated with risk for OFCs in offspring. This population-based case-control study included 103 newborns affected by OFCs with available placental tissues and 206 controls randomly selected from 509 non-malformed newborns with available placenta samples, recruited in five rural counties in northern China. Sociodemographic information was collected using a structured questionnaire in face-to-face interviews. The concentrations of Hg, Cd, Pb, and As in placental tissues were analyzed using an inductively coupled plasma-mass spectrometry in helium mode. The median concentrations of Hg (7.4 ng/g), Cd (57.1 ng/g), and Pb (96.1 ng/g) were all statistically significantly higher in OFC cases than in controls (Hg 5.5 ng/g, Cd 38.6 ng/g, and Pb 67.9 ng/g, respectively); no differences were observed between the two groups in median concentrations of As. Concentrations above the median for all subjects were associated with a 2.33-fold (95% confidence interval [CI] 1.33–2.09) increased OFC risk for Cd and a 3.08-fold (95% CI 1.74–5.47) increased risk for Pb. The risk for OFCs increased with concentration tertiles, with an adjusted odds ratio of 3.06 (95% CI 1.36–6.88) for the second tertile and 8.18 (95% CI 6.64–18.37) for the highest tertile of Cd, and 3.88 (95% CI 1.78–8.42) for the second tertile and 5.17 (95% CI 2.37–11.29) for the highest tertile of Pb. The association between Hg concentration and OFC risk was borderline nonsignificant after adjusting for confounding factors. Prenatal exposure to Cd and Pb, as reflected by their concentrations in placental tissues, is associated with an increased risk for neonatal OFCs.
Show more [+] Less [-]Preventive use of berberine in inhibition of lead-induced renal injury in rats
2018
Hasanein, Parisa | Riahi, Hassan
The kidney is one of the main organs affected by lead toxicity. We investigated the effects of berberine on lead-induced nephrotoxicity in adult male Wistar rats. Animals received an aqueous solution of lead acetate (500 mg Pb/L in the drinking water) and/or berberine (50 mg/kg, i.g.) for 8 weeks. Lead caused an increase in malondialdehyde (P < 0.001) and total oxidant status (P < 0.01), and a decrease in reduced glutathione (P < 0.001), catalase (P < 0.01), superoxide dismutase (P < 0.001), and total antioxidant capacity (P < 0.05). Berberine prevented the prooxidant and antioxidant imbalance induced by lead (P < 0.001). Berberine corrected the increased relative kidney weight (P < 0.05) and biomarkers of renal function (creatinine (P < 0.001), urea (P < 0.05), uric acid (P < 0.001), albumin (P < 0.01), and total protein (P < 0.05)) in lead group. It also attenuated lead-induced abnormal renal structure. The results confirmed renoprotective effects of berberine in an animal model of lead-induced nephrotoxicity by molecular, biochemical, and histopathological analysis through inhibiting lipid peroxidation and enhancing antioxidant defense system mechanisms. Therefore, berberine makes a good candidate to protect against the deleterious effect of chronic lead intoxication.
Show more [+] Less [-]Evidence of oxidative stress after continuous exposure to Wi-Fi radiation in rat model
2018
Kamali, Kasra | Taravati, Ali | Sayyadi, Shayan | Gharib, Fatemeh zahra | Maftoon, Houman
Exposure to electromagnetic radiation (EMR) is rapidly increasing in everyday environment, consequently conferring potential health effects. Oxidative stress is emerging as a mechanism implicated in pathophysiology and progression of various diseases. To our knowledge, no report has been made on the status of antioxidant redox systems after continuous exposure to radiofrequency radiation emitted from a Wi-Fi access point in animal model so far. Therefore, we aimed to continuously subject rats in the experimental group to radiofrequency (RF) radiation emitted from a commercially available Wi-Fi device. Male Wister rats were exposed to 2.45 GHz RF radiation emitted from a Wi-Fi for 24 h/day for 10 consecutive weeks. In order to assess the change in antioxidant redox system of plasma after continuous exposure to a Wi-Fi device, the total antioxidant capacity of plasma, level of thiobarbituric acid reactive substances, concentration of reduced glutathione (GSH), and activity of different enzymatic antioxidants, e.g., superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px], and glutathione S-transferase [GST], were measured. In the Wi-Fi exposed group, a significant decrease was detected in total antioxidant capacity of plasma and the activities of several antioxidant enzymes, including CAT, GSH-Px, and SOD (P < 0.05). Meanwhile, the GST activity was significantly increased in this group (P < 0.05). However, no significant changes were found in GSH and TBARS levels following exposure to RF radiation. According to the results, oxidative defense system in rats exposed to Wi-Fi signal was significantly affected compared to the control group. Further studies are needed to better understand the possible biological mechanisms of EMR emitted from Wi-Fi device and relevant outcomes.
Show more [+] Less [-]Exposure marker discovery of di(isononyl)cyclohexane-1,2-dicarboxylate using two mass spectrometry-based metabolite profiling data processing methods
2018
Shih, Chia-Lung | Liao, Pao-Mei | Hsu, Jen-Yi | Chung, Yi-Ning | Zgoda, VictorG. | Liao, Pao-Chi
Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is a plasticizer used in polyvinyl chloride (PVC) products, such as toys and food packaging. Because the use of DINCH is on the rise, the risk of human exposure to this chemical may likewise increase. Discovering markers for assessing human chemical exposure is difficult because the metabolism of chemicals within humans is complex. In this study, two mass spectrometry (MS)-based metabolite profiling data processing methods, the mass defect filter (MDF) method and the signal mining algorithm with isotope tracing (SMAIT) method, were used for DINCH metabolite discovery, and 110 and 18 potential DINCH metabolite signal candidates were discovered, respectively, from in vitro DINCH incubation samples. Of these, the 21 signals were validated as tentative exposure marker signals in a rat model. Interestingly, the two methods generated rather different sets of DINCH exposure markers. Five of the 21 tentative exposure marker signals were verified as the probable DINCH structure-related metabolite signals based on their MS/MS product ion profiles. These five signals were detected in at least one human urine sample. Of the five probable DINCH structure-related metabolite signals, two novel signals might be suitable exposure markers that should be further investigated for their application in human DINCH exposure assessments. These observations indicate that the MDF and SMAIT methods may be used to discover a relatively different set of potential DINCH exposure markers.
Show more [+] Less [-]