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Screening and validation of biomarkers for cadmium-induced liver injury based on targeted bile acid metabolomics
2022
Tian, Meng | Yan, Jun | Zhang, Honglong | Wei, Yuhui | Zhang, Mingtong | Rao, Zhi | Zhang, Mingkang | Wang, Haiping | Wang, Yanping | Li, Xun
Although cadmium (Cd) is a toxic heavy metal that reportedly causes liver injury, few studies have investigated biomarkers of Cd-induced liver injury. The purpose of this study is to investigate the role of bile acid (BA) in Cd-induced liver injury and determine reliable and sensitive biochemical parameters for the diagnosis of Cd-induced liver injury. In this study, 48 Sprague-Dawley rats were randomly divided into six groups and administered either normal saline or 2.5, 5, 10, 20, and 40 mg/kg/d cadmium chloride for 12 weeks. A total of 403 subjects living in either a control area (n = 135) or Cd polluted area (n = 268) of Dongdagou-Xinglong (DDGXL) cohort were included, a population with long-term low Cd exposure. The BA profiles in rats' liver, serum, caecal contents, faeces, and subjects' serum were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS). Changes in rats' and subjects' liver injury indices, rats' liver pathological degeneration, and rats' liver and subjects’ blood Cd levels were also measured. Cadmium exposure caused cholestasis and an increase in toxic BAs, leading to liver injury in rats. Among them, glycoursodeoxycholic acid (GUDCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and taurodeoxycholate acid (TDCA) are expected to be potential biomarkers for the early detect of Cd-induced liver injury. Serum BAs can be used to assess Cd-induced liver injury as a simple, feasible, and suitable method in rats. Serum GUDCA, GLCA, TDCA, and TLCA were verified to be of value to evaluate Cd-induced liver injury and Cd exposure in humans. These findings provided evidence for screening and validation of additional biomarkers for Cd-induced liver injury based on targeted BA metabolomics.
Show more [+] Less [-]Effects of long-term and low-concentration exposures of benzene and formaldehyde on mortality of Drosophila melanogaster
2022
Li, Xiaoying | Li, Zhenhai | Shen, Hao | Zhao, Haishan | Qin, Guojun | Xue, Jingchuan
Single-chemical thresholds cannot comprehensively evaluate the risk of chemical mixture exposure in indoor air. Moreover, a large number of researches have focused on short-term and high-concentration co-exposure scenarios related to different species, based on diverse endpoints, which hampers the application and improvement of existing risk evaluation models of chemical mixture exposures. More importantly, current risk evaluation models are not user-friendly for construction practitioners who do not have sufficient toxicological knowledge. Therefore, in this study, an inhalation experiment system and a hazard index (HI) were developed to investigate the risks associated with low-concentration and long-term inhalation exposure scenarios of formaldehyde and benzene, individually and combined, based on Drosophila melanogaster mortality. The results showed that the system exhibited good reproducibility in providing stable exposure concentrations during D. melanogaster life cycle. Furthermore, in a range of experimental concentrations, the interaction between formaldehyde and benzene was additive or synergistic, which was concentration- and ratio-dependent. This study is of great significance in harmonising and providing toxicity data under long-term and low-concentration exposure scenarios, which is beneficial for establishing a new user-friendly risk evaluation model for indoor chemical mixture exposures. It should be noted that the proposed HI value could indicate the hazard degrees of long-term inhalation exposures of formaldehyde and benzene, individually and combined, to D. melanogaster. However, the applicability of this index requires further experiments to evaluate the exposure risks of other volatile organic compounds (VOCs) to D. melanogaster.
Show more [+] Less [-]Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage
2021
Das, Sourav Kumar | Ali, Manjoor | Shetake, Neena G. | Dumpala, Rama Mohan R. | Pandey, Badri N. | Kumar, Amit
Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1–100 μg/ml, 24–72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity.
Show more [+] Less [-]Biofilm influenced metal accumulation onto plastic debris in different freshwaters
2021
Liu, Zhilin | Adyel, Tanveer M. | Miao, Lingzhan | You, Guoxiang | Liu, Songqi | Hou, Jun
Microbial biofilms can rapidly colonize plastic debris in aquatic environments and subsequently, accumulate chemical pollutants from the surrounding water. Here, we studied the microbial colonization of different plastics, including polyethylene terephthalate (PET), polypropylene (PP), polyvinyl chloride (PVC), and polyethylene (PE) exposed in three freshwater systems (the Qinhuai River, the Niushoushan River, and Donghu Lake) for 44 days. We also assessed the biofilm mass and associated metals attached to plastics. The plastics debris characteristics, such as contact angle and surface roughness, greatly affected the increased biofilm biomass. All types of metal accumulation onto the plastic substrate abundances significantly higher than the concentrations of heavy metal in the water column, such as Ba (267.75 μg/g vs. 42.12 μg/L, Donhu Lake), Zn (254 μg/g vs. 0.023 μg/L the Qinhuai River), and Cr (93.75 μg/g vs. 0.039 μg/L, the Niushoushan River). Compared with other metals, the heavy metal Ba, Cr and Zn accumulated easily on the plastic debris (PET, PP, PVC, and PE) at all incubation sites. Aquatic environmental factors (total nitrogen, total phosphorus, and suspended solids concentrations) largely shaped metal accumulation onto plastic debris compared with plastic debris properties.
Show more [+] Less [-]Occurrence of neonicotinoids and fipronil in estuaries and their potential risks to aquatic invertebrates
2019
Hano, Takeshi | Ito, Katsutoshi | Ohkubo, Nobuyuki | Sakaji, Hideo | Watanabe, Akio | Takashima, Kei | Satō, Taku | Sugaya, Takuma | Matsuki, Kosuke | Onduka, Toshimitsu | Ito, Mana | Somiya, Rei | Mochida, Kazuhiko
This study aimed to evaluate and qualify field-based potential risks of seven neonicotinoid and phenylpyrazole (fipronil) insecticides on aquatic invertebrates, including estuary-resident marine crustaceans. One hundred and ninety-three estuarine water samples, with salinity ranging from 0.5 to 32.7, were collected from four estuarine sites in the Seto Inland Sea of Japan, in 2015–2018 and the insecticide levels were measured. Five neonicotinoid and fipronil insecticides were successfully identified, and their occurrence varied temporally. Marine crustaceans were simultaneously harvested every month from one of the estuarine water sampling sites in 2015–2017. Three predominant crustacean species, kuruma prawn (Penaeus japonicus), sand shrimp (Crangon uritai), and mysid (Neomysis awatschensis), were captured and their seasonal presence was species independent. A 96-h laboratory toxicity study with the insecticides using kuruma prawn, sand shrimp, and a surrogate mysid species (Americamysis bahia) indicated that fipronil exerted the highest toxicity to the three crustaceans. Using both toxicity data and insecticide occurrence in estuarine water (salinity ≥10, n = 169), the potential risks on the three marine crustaceans were quantified by calculating the proportion of mixture toxicity effects (Pₘᵢₓ). The Pₘᵢₓ of seven neonicotinoids on the crustaceans was less than 0.8%, which is likely to be too low to indicate adverse effects caused by the insecticides. However, short temporal detection of fipronil (exclusively in June and July) significantly affected the Pₘᵢₓ, which presented the maximal Pₘᵢₓ values of 21%, 3.4%, and 72% for kuruma prawn, sand shrimp, and mysid, respectively, indicating a significant effect on the organisms. As for estuarine water (salinity <10), some water samples contained imidacloprid and fipronil exceeding the freshwater benchmarks for aquatic invertebrates. The present study provides novel insights into the seasonally varying risks of insecticides to estuarine crustaceans and highlights the importance of considering whether ecological risk periods coincide with crustacean presence.
Show more [+] Less [-]Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice
2017
Liu, Qian | Shao, Wentao | Zhang, Chunlan | Xu, Cheng | Wang, Qihan | Liu, Hui | Sun, Haidong | Jiang, Zhaoyan | Gu, Aihua
Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p’-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human.
Show more [+] Less [-]Submerged macrophytes successfully restored a subtropical aquacultural lake by controlling its internal phosphorus loading
2021
Li, Yang | Wang, Ligong | Chao, Chuanxin | Yu, Hongwei | Yu, Dan | Liu, Chunhua
Intensive aquaculture has largely changed the global phosphorus (P) flow and become one of the main reasons for the eutrophication of global aquatic ecosystem. Artificial planting submerged macrophytes has attracted enormous interest regarding the restoration of eutrophic lakes. However, few large-scale (>80 km²) studies have focused on the restoration of aquatic vegetation in the subtropical lakes, and the mechanism underlying the restrain of sediment P release by macrophytes remains unknown. In this study, field surveys and the diffusive gradients in thin films (DGT) technique were used to elucidate the effects of macrophytes on internal P loading control in a typical eutrophic aquacultural lake. Results showed that half of the P content in overlying water and sediments, particularly dissolved P in overlying water and calcium bound P (Ca–P) in sediment, were removed after restoration. Temperature, as well as dissolved oxygen (DO) and P concentration gradients near the sediment-water interface (SWI) jointly controlled the release of labile P from surface sediments. Submerged macrophytes can effectively inhibit the release of sediment P into the overlying water, which depended on DO concentration in the bottom water. Future restoration projects should focus on the temperature response of submerged macrophytes of different growth forms (especially canopy-forming species) to avoid undesirable restoration effects. Our results complement existing knowledge about submerged macrophytes repairing subtropical P-contaminated lakes and have positive significance for lake restoration by in situ phytoremediation.
Show more [+] Less [-]Personal exposure to PM2.5 constituents associated with gestational blood pressure and endothelial dysfunction
2019
Xia, Bin | Zhou, Yuhan | Zhu, Qingyang | Zhao, Yingya | Wang, Ying | Ge, Wenzhen | Yang, Qing | Zhao, Yan | Wang, Pengpeng | Si, Jingyi | Luo, Ranran | Li, Jialin | Shi, Huijing | Zhang, Yunhui
Ambient fine particulate matter (PM2.5) pollution has been implicated in the development of hypertensive disorders of pregnancy. However, evidence on the effects of PM2.5-derived chemical constituents on gestational blood pressure (BP) is limited, and the potential mechanisms underlying the association remain unclear. In this study, we repeated three consecutive 72-h personal air sampling and BP measurements in 215 pregnant women for 590 visits during pregnancy. Individual PM2.5 exposure level was assessed by gravimetric method and 28 PM2.5 chemical constituents were analyzed by ED-XRF method. Plasma biomarkers of endothelial function and inflammation were measured using multiplexed immunoassays. Robust multiple linear regression models were used to estimate the associations among personal PM2.5 exposure and chemical constituents, BP changes (compared with pre-pregnancy BP) and plasma biomarkers. Mediation analyses were performed to evaluate underlying potential pathways. Result showed that exposure to PM2.5 was significantly associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in the early second trimester. Meanwhile, elevated concentration of lead (Pb) constituent in PM2.5 was significant associated with increases in DBP and MAP after adjusting for PM2.5 total mass. PM2.5 and Pb constituent also presented positive associations with plasma biomarkers of endothelial function (ET-1, E-selectin, ICAM-1) and inflammation (IL-1β, IL-6, TNFα) significantly. After multiple adjustment, elevated ET-1 and IL-6 were significantly correlated with increased gestational BP, and respectively mediated 1.24%–25.06% and 7.01%–10.69% of the increased BP due to PM2.5 and Pb constituent exposure. In conclusion, our results suggested that personal exposure to PM2.5 and Pb constituent were significantly associated with increased BP during pregnancy, and the early second trimester might be the sensitive window of PM2.5 exposure. The endothelial dysfunction and elevated inflammation partially mediated the effect of PM2.5 and Pb constituent on BP during pregnancy.
Show more [+] Less [-]Metal composition of fine particulate air pollution and acute changes in cardiorespiratory physiology
2014
Cakmak, Sabit | Dales, Robert | Kauri, Lisa Marie | Mahmud, Mamun | Van Ryswyk, Keith | Vanos, Jennifer | Liu, Ling | Kumarathasan, Premkumari | Thomson, Errol | Vincent, Renaud | Weichenthal, Scott
Studying the physiologic effects of components of fine particulate mass (PM2.5) could contribute to a better understanding of the nature of toxicity of air pollution.We examined the relation between acute changes in cardiovascular and respiratory function, and PM2.5-associated-metals.Using generalized linear mixed models, daily changes in ambient PM2.5-associated metals were compared to daily changes in physiologic measures in 59 healthy subjects who spent 5-days near a steel plant and 5-days on a college campus.Interquartile increases in calcium, cadmium, lead, strontium, tin, vanadium and zinc were associated with statistically significant increases in heart rate of 1–3 beats per minute, increases of 1–3 mmHg in blood pressure and/or lung function decreases of up to 4% for total lung capacity.Metals contained in PM2.5 were found to be associated with acute changes in cardiovascular and respiratory physiology.
Show more [+] Less [-]Pro-inflammatory effects and oxidative stress in lung macrophages and epithelial cells induced by ambient particulate matter
2013
Michael, S. | Montag, M. | Dott, W.
The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0–100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers.
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