خيارات البحث
النتائج 1 - 10 من 174
High inter-species differences of 12378-polychlorinated dibenzo-p-dioxin between humans and mice
2020
Dong, Zhaomin | Ben, Yujie | Li, Yu | Li, Tong | Wan, Yi | Hu, Jianying
Although huge interspecies differences in the response to dioxins have been acknowledged, toxic equivalency factors derived from rodent studies are often used to assess human health risk. To determine interspecies differences, we first developed a toxicokinetic model in humans by measuring dioxin concentrations in environmental and biomonitoring samples from Southern China. Significant positive correlations between dioxin concentrations in blood and age were observed for seven dioxin congeners, indicating an age-dependent elimination rate. Based on toxicokinetic models in humans, the half-lives of 15 dioxin congeners were estimated to be 1.60–28.55 years. In consideration that the highest contribution to total toxic equivalency in blood samples was by 12378-polychlorinated dibenzo-p-dioxin (P₅CDD), this study developed a physiologically based pharmacokinetic (PBPK) model of 12378-P₅CDD levels in the liver, kidney, and fat of C57/6J mice exposed to a single oral dose, and the half-life was estimated to be 26.1 days. Based on estimated half-lives in humans and mice, we determined that the interspecies difference of 12378-P₅CDD was 71, much higher than the default usually used in risk assessment. These results could reduce the uncertainty human risk assessment of 12378-P₅CDD, and our approach could be used to estimate the interspecies differences of other dioxin congeners.
اظهر المزيد [+] اقل [-]Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver
2020
Jiao, Yaqi | Tao, Yue | Yang, Yang | Diogene, Tuyiringire | Yu, Hui | He, Ziqing | Han, Wei | Chen, Zhaobo | Wu, Pan | Zhang, Ying
In this paper, the acute toxicity of monobutyl phthalate (MBP), the main hydrolysis product of dibutyl phthalate, on adult zebrafish liver antioxidant system was studied. Compared the toxicity effect of MBP and DBP by histopathology and apoptosis experiments, we speculated that the toxic effects of DBP on animals may be caused by its metabolite MBP. The results indicated that the antioxidant Nrf2-Keap1 pathway was insufficient to resist MBP-induced hepatotoxicity and led to an imbalance of membrane ion homeostasis and liver damage. Decreased cell viability, significant tissue lesions and early hepatocyte apoptosis were observed in the zebrafish liver in MBP exposure at high concentration (10 mg/L). The activities of antioxidant enzymes and ATPases in zebrafish liver were inhibited with increased malondialdehyde (MDA) content and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Integrated biomarker response (IBR) calculation results indicated that MBP mainly inhibited catalase (CAT) activity. Simultaneously, the expression of antioxidant-related genes (SOD, CAT, GPx, Nrf2, HO-1) was down-regulated, while apoptosis-related genes (p53, bax, cas3) were significantly up-regulated.
اظهر المزيد [+] اقل [-]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 [-]Muscle melanisation of southern sand flathead (Platycephalus bassensis) in the Tamar Estuary, Tasmania, Australia
2020
Stocker, Clayton W. | Haddy, James | Lyle, Jeremy | Nowak, Barbara F.
Tasmanian recreational fishers have reported the presence of dark pigmentations in the usually white fillets of southern sand flathead (Platycephalus bassensis), a phenomenon known as muscle melanisation. Based on histology, it is suggested that eumelanin and pheomelanin are involved in the occurrence of the phenomenon. A gross melanisation scoring system was validated through a comparison with an image analysis technique, that quantified the percentage surface area of the fillets affected by muscle melanisation. The occurrence of muscle melanisation was most severe in fish inhabiting Deceitful Cove, Tamar Estuary. This indicated that muscle melanisation in P. bassensis may be caused by yet to be identified site specific factors. No significant relationships were evident between the percentage surface area of melanised muscle with condition index, age, sex, maturation stage, fish weight, fish length and size of melano-macrophage centres in the liver or spleen. Overall, this study has provided critical information that will frame the direction and focus of future P. bassensis muscle melanisation research.
اظهر المزيد [+] اقل [-]Biotransformation and tissue bioaccumulation of 8:2 fluorotelomer alcohol in broiler by oral exposure
2020
Chen, Dongmei | Zhao, Ying | Xu, Wei | Pan, Yuanhu | Wei, Qu | Xie, Shuyu
In order to examine whether 8:2 FTOH exposure would lead to a contamination risk of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in broiler derived food, the biotransformation, and tissue distribution and accumulation of 8:2 FTOH following oral exposure in male broilers were investigated. The main metabolites of 8:2 FTOH in plasma and six tissues (muscle, liver, kidney, fat, heart, and lungs) identified by LC-Q-TOF were 2-perfluorooctyl ethanoic acid (8:2 FTCA), 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA), 3-perfluoroheptyl propanoic acid (7:3 FTCA), perfluoropentanoic acid (PFPeA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), 8:2 FTOH glucuronide conjugate, and 8:2 FTOH sulfate conjugate. The tissue distribution and bioaccumulation of 8:2 FTOH and its unconjugated metabolites were determinated by LC-MS/MS. 8:2 FTOH was quickly depleted in plasma and all six tested tissues, while PFOA, PFNA, and 7:3 FTCA showed strong accumulation in blood and all six examined tissues and were eliminated more slowly than the other metabolites. The tissues with the highest accumulation levels for 8:2 FTOH and its metabolites were heart, kidneys and liver, and the tissue with the lowest accumulation levels was muscle. The elimination half-lifes of PFNA in kidney and 7:3 FTCA in lung were longer compared to those of other metabolites in all six determined tissues. Thus, PFNA and 7:3 FTCA can be selected as potential biomonitoring markers after 8:2 FTOH exposure. This study has improved our understanding of 8:2 FTOH biotransformation and tissue bioaccumulation in broilers, which will help us monitor human exposure risk via food derived from broilers polluted by 8:2 FTOH.
اظهر المزيد [+] اقل [-]High-content screening in zebrafish identifies perfluorooctanesulfonamide as a potent developmental toxicant
2020
Dasgupta, Subham | Reddam, Aalekhya | Liu, Zekun | Liu, Jinyong | Volz, David C.
Per- and polyfluoroalkyl substances (PFASs) have been used for decades within industrial processes and consumer products, resulting in frequent detection within the environment. Using zebrafish embryos, we screened 38 PFASs for developmental toxicity and revealed that perfluorooctanesulfonamide (PFOSA) was the most potent developmental toxicant, resulting in elevated mortality and developmental abnormalities following exposure from 6 to 24 h post fertilization (hpf) and 6 to 72 hpf. PFOSA resulted in a concentration-dependent increase in mortality and abnormalities, with surviving embryos exhibiting a >12-h delay in development at 24 hpf. Exposures initiated at 0.75 hpf also resulted in a concentration-dependent delay in epiboly, although these effects were not driven by a specific sensitive window of development. We relied on mRNA-sequencing to identify the potential association of PFOSA-induced developmental delays with impacts on the embryonic transcriptome. Relative to stage-matched vehicle controls, these data revealed that pathways related to hepatotoxicity and lipid transport were disrupted in embryos exposed to PFOSA from 0.75 to 14 hpf and 0.75 to 24 hpf. Therefore, we measured liver area as well as neutral lipids in 128-hpf embryos exposed to vehicle (0.1% DMSO) or PFOSA from 0.75 to 24 hpf and clean water from 24 to 128 hpf, and showed that PFOSA exposure from 0.75 to 24 hpf resulted in a decrease in liver area and increase in yolk sac neutral lipids at 128 hpf. Overall, our findings show that early exposure to PFOSA adversely impacts embryogenesis, an effect that may lead to altered lipid transport and liver development.
اظهر المزيد [+] اقل [-]Tissue-specific bioaccumulation, metabolism and excretion of tris (2-ethylhexyl) phosphate (TEHP) in rare minnow (Gobiocyprisrarus)
2020
Hou, Rui | Xu, Yiping | Rao, Kaifeng | Feng, Chenglian | Wang, Zijian
Tris (2-ethylhexyl) phosphate (TEHP) is one of the most commonly used organophosphorus flame retardant (OPFR) analogues and is commonly detected in surface water and sediments. Limited information is available about the metabolic pathway or metabolite formation related to TEHP in fish. In this study, rare minnows (Gobiocyprisrarus) were exposed to TEHP in static water for 30 d to investigate the bioaccumulation and metabolite distribution in the fish muscle, liver, kidney, gill, GI-tract, ovary and testis. Based on the estimated kᵤₚ,ₚₐᵣₑₙₜ and kd,ₚₐᵣₑₙₜ values, the bioconcentration factors (BCFₚₐᵣₑₙₜ) of TEHP in fish tissues were calculated in the order of kidney > ovary ≈ liver ≈ testis > gill ≈ GI-tract > muscle; this finding was consistent with the results of our previous study on other alkyl-substituted OPFRs. In addition, this study identified the metabolic profiles of TEHP in the liver. TEHP was oxidatively metabolized by the fish to a dealkylated metabolite (di 2-ethylhexyl phosphate; DEHP) and hydroxylated TEHP (OH-TEHP). OH-TEHP further underwent extensive phase II metabolism to yield glucuronic acid conjugates. DEHP was mainly distributed in rare minnow in the following order: liver > GI-tract > kidney ≫ other tissues. However, the metabolite showed lower accumulation potential in fish tissues than TEHP, with metabolite parent concentration factors (MPCFs) for DEHP of less than 0.1 in all the investigated tissues. The BCFₚₐᵣₑₙₜ values of TEHP in various fish tissues were only 9.0 × 10⁻³-7.2 × 10⁻⁴ times its estimated tissue-water partition coefficient (Kₜᵢₛₛᵤₑ₋wₐₜₑᵣ) values based on tissue lipid, protein and water contents, which indicated the significance of biotransformation in reducing the bioaccumulation potential of TEHP in fish. The toxicokinetic data in the present study help in understanding the tissue-specific bioaccumulation and metabolism pathways of TEHP in fish and highlight the importance of toxicology research on TEHP metabolites in aquatic organisms.
اظهر المزيد [+] اقل [-]Long-term bisphenol S exposure aggravates non-alcoholic fatty liver by regulating lipid metabolism and inducing endoplasmic reticulum stress response with activation of unfolded protein response in male zebrafish
2020
Qin, Jingyu | Ru, Shaoguo | Wang, Weiwei | Hao, Liping | Ru, Yiran | Wang, Jun | Zhang, Xiaona
Environmental chemical exposures have been implicated as risk factors for the development of non-alcoholic fatty liver (NAFLD). Bisphenol S (BPS), widely used in multitudinous consumer products, could disrupt lipid metabolism in the liver. This study aimed at examining the hypothesis that long-term exposure to BPS promotes the development of liver fibrosis and inflammation by means of the application of a semi-static exposure experiment that exposed zebrafish to 1, 10, and 100 μg/L BPS from 3 h post fertilization to 120 day post fertilization. Results showed that the 120-d BPS exposure elevated plasma aspartate aminotransferase and alanine aminotransferase activities, increased triacylglycerol (TAG) and total cholesterol levels in male liver, and even induced hepatic apoptosis and fibrosis. Hepatic lipid accumulation observed in the 30-d BPS-exposed zebrafish was recovered after a 90-d depuration phase, thereby indicating that long-term BPS exposure promotes the progression of simple steatosis to non-alcoholic steatohepatitis. Furthermore, BPS exposure for 120-d promoted the synthesis of TAG and lipotoxic free fatty acids by elevating the transcription of srebp1, acc, fasn, and elovl6, induced endoplasmic reticulum (ER) stress with increasing expression levels of unfolded protein response (UPR) genes (perk, hsp5, atf4a, and ddit3), and then stimulated the expression of two key autophagy genes (atg3 and lc3) and inflammatory genes (il1b and tnfα). It is indicated that BPS can induce the development of steatohepatitis via the activation of the PERK-ATF4a pathway of the UPR. Data gathered suggest that environmental pollutants-induced ER stress with the activation of UPR can potentially trigger the NAFLD development in males. Overall, our study provided new sights into understanding of the adverse health effects of metabolism disrupting chemicals.
اظهر المزيد [+] اقل [-]Weathered Mississippi Canyon 252 crude oil ingestion alters cytokine signaling, lowers heterophil:lymphocyte ratio, and induces sickness behavior in zebra finches (Taeniopygia guttata)
2020
Goodchild, Christopher G. | Love, Ashley C. | Krall, Jeffrey B. | DuRant, Sarah E.
The Deepwater Horizon (DWH) oil spill caused an estimated 100,000 bird mortalities. However, mortality estimates are often based on the number of visibly oiled birds and likely underestimate the true damage to avian populations as they do not include toxic effects from crude oil ingestion. Elevated susceptibility to disease has been postulated to be a significant barrier to recovery for birds that have ingested crude oil. Effective defense against pathogens involves integration of physiological and behavioral traits, which are regulated in-part by cytokine signaling pathways. In this study, we tested whether crude oil ingestion altered behavioral and physiological aspects of disease defense in birds. To do so, we used artificially weathered Mississippi Canyon 242 crude oil to orally dose zebra finches (Taeniopygia guttata) with 3.3 mL/kg or 10 mL/kg of crude oil or a control (peanut oil) for 14 days. We measured expression of cytokines (interleukin [IL]-1β, IL-6, IL-10) and proinflammatory pathways (NF-κB, COX-2) in the intestine, liver, and spleen (tissues that exhibit pathology in oil-exposed birds). We also measured heterophil:lymphocyte (H:L) ratio and complement system activity, and video-recorded birds to analyze sickness behavior. Finches that ingested crude oil exhibited tissue-specific changes in cytokine mRNA expression. Proinflammatory cytokine expression decreased in the intestine but increased in the liver and spleen. Birds exposed to crude oil had lower H:L ratios compared to the control on day 14, but there were no differences in complement activity among treatments. Additionally, birds exposed to 10 mL/kg crude oil had reduced activity, indicative of sickness behavior. Our results suggest cytokines play a role in mediating physiological and behavioral responses to crude oil ingestion. Although most avian population damage assessments focus on mortality caused by external oiling, crude oil ingestion may also indirectly affect survival by altering physiological and behavioral traits important for disease defense.
اظهر المزيد [+] اقل [-]Seasonal factors driving biochemical biomarkers in two fish species from a subtropical reservoir in southern Brazil: An integrated approach
2020
Blank do Amaral, Aline Monique | Kuhn de Moura, Letícia | de Pellegrin, Dionatan | Guerra, Luciana Joner | Cerezer, Felipe Osmari | Saibt, Nathália | Prestes, Osmar Damian | Zanella, Renato | Loro, Vania Lucia | Clasen, Barbara
Reservoirs are lentic man-made waterbodies resulting from river damming processes. Pollutants coming from adjacent areas can accumulate in the water and sediment of these modified freshwater environments. Fish are often found in reservoirs occupying several trophic niches. Biochemical biomarkers are early warning signals of environmental disturbance to an organism. It is essential to understand how pollutants, abiotic variables and biochemical biomarker responses behave throughout the seasons to implement biomonitoring programs. Loricariichthys anus and Geophagus brasiliensis were collected, and abiotic variables were seasonally measured for one year, at six sampling sites in Passo Real reservoir, in a subtropical region of Southern Brazil. Biochemical biomarkers were analyzed in four tissues of both fish species, as well as metal and pesticide concentrations in the reservoir’s water and sediment. Redundancy analysis (RDA) was carried out to find the temporal relationship between biomarkers and environmental variables. RDA has clearly shown the separation of seasons for both species. Azoxystrobin, simazine and propoxur were the pesticides mostly contributing to the variation, whereas metals had lesser contribution to it. Seasonality appears to be the main factor explaining biomarkers’ variability. PERMANOVA has confirmed the effect of temperature and dissolved oxygen on biomarkers of both fish species. Thus, it is hard to differentiate if the fluctuation in biomarkers’ responses only reflects the normal state of organisms or it is a biological consequence from negative effects of fish exposure to several types of pollution (sewage, pesticides, and fertilizers) entering this aquatic system. In this study, to circumvent the seasonality issue on biomonitoring, the analysis of biomarkers on these fish should not be carried out in organs directly affected by temperature (such as liver and gills), or during reproduction periods (mainly in Spring).
اظهر المزيد [+] اقل [-]