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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.
Afficher plus [+] Moins [-]One uncertainty factor does not fit all: Identifying mode of action and species specific acute to chronic ratios for aquatic life
2020
Wang, Zhen | Berninger, Jason P. | Yau, Ching | Brooks, Bryan W.
In ecological risk assessment, acute to chronic ratio (ACR) uncertainty factors are routinely applied to acute mortality benchmarks to estimate chronic toxicity thresholds. To investigate variability of aquatic ACRs, we first compiled and compared 56 and 150 pairs of acute and subchronic/chronic growth/reproductive toxicity data for fishes (Pimephales promelas (53), Danio rerio (2), and Oryzias latipes (1)) and the crustacean Daphnia magna, respectively, for 172 chemicals with different modes of action (MOA). We found that there were only significant relationships between P. promelas acute median lethal concentrations and growth lowest-observed effect concentrations for class 1 (nonpolar narcosis) chemicals, though significant relationships were demonstrated for D. magna to all Verhaar et al. MOA classes (Class 1: nonpolar narcosis, Class 2: polar narcosis, Class 3: reactive chemicals, and Class 4: AChE inhibitors and estrogenics). Probabilistic ecological hazard assessment using chemical toxicity distributions was subsequently employed for each MOA class to estimate acute and chronic thresholds, respectively, to identify MOA and species specific ecological thresholds of toxicological concern. Finally, novel MOA and species specific ACRs using both chemical toxicity distribution comparison and individual ACR probability distribution approaches were identified using representative MOA and chemical categories. Our data-driven approaches and newly identified ACR values represent robust alternatives to application of default ACR values, and can also support future research and risk assessment and management activities for other chemical classes when toxicity information is limited for chemicals with specific MOAs within invertebrates and fish.
Afficher plus [+] Moins [-]An ICT-based fluorescent probe with a large Stokes shift for measuring hydrazine in biological and water samples
2020
Zhu, Meiqing | Xu, Yimin | Sang, Linfeng | Zhao, Zongyuan | Wang, Lijun | Wu, Xiaoqin | Fan, Fugang | Wang, Yi | Li, Hui
As a strong reductant and highly active alkali, hydrazine (N2H4) has been widely used in chemical industry, pharmaceutical manufacturing and agricultural production. However, its high acute toxicity poses a threat to ecosystem and human health. In the present study, a ratiometric fluorescent probe for the detection of N2H4 was designed, utilizing dicyanoisophorone as the fluorescent group and 4-bromobutyryl moiety as the recognition site. 4-(2-(3-(dicyanomethylene)-5,5-dimethylcyclohex-1-enyl) phenyl 4-brobutanoate (DDPB) was readily synthesized and could specially sense N2H4 via an intramolecular charge transfer (ICT) pathway. The cyclization cleavage reaction of N2H4 with a 4-bromobutyryl group released phenolic hydroxyl group and reversed the ICT process between hydroxy group and fluorophore, turning on the fluorescence in the DDPB-N2H4 complexes. DDPB exhibits a low cytotoxicity, reasonable cell permeability, a large Stokes shift (186 nm) and a low detection limit (86.3 nM). The quantitative determination of environmental water systems and the visualization fluorescence of DDPB test strips provides a strong evidence for the applications of DDPB. In addition, DDPB is suitable for the fluorescence imaging of exogenous N2H4 in HeLa cells and zebrafish.
Afficher plus [+] Moins [-]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.
Afficher plus [+] Moins [-]Environmental co-exposure to TBT and Cd caused neurotoxicity and thyroid endocrine disruption in zebrafish, a three-generation study in a simulated environment
2020
Li, Ping | Li, Zhi-Hua
Although the coexistence of heavy metals and environmental hormones always occur in aquatic environment, the information of the combined impacts remains unclear. To explore the multi-generational toxicity of cadmium (Cd) and tributyltin (TBT), adult zebrafish (Danio rerio) (F0) were exposed to different treated groups (100 ng/l Cd, 100 ng/l TBT and their mixture) for 90 d, with their offspring (F1 and F2) subsequently reared in the same exposure solutions corresponding to their parents. Both developmental neurotoxicity and thyroid disturbances were examined in the three (F0, F1, and F2) generations. Our results showed that co-exposure to Cd and TBT induced the developmental neurotoxicity in F1 and F2 generations, reflected by the significant lower levels of neurotransmitters (dopamine and serotonin) and the inhibited acetylcholinesterase (AChE) activities. And the thyroid endocrine disruption were observed in the two-generations larval offspring by parental exposure to Cd and/or TBT, including the significantly decreasing levels of thyroid hormones and the down-regulated the expression of genes involved in the hypothalamus-pituitary-thyroid axis, compared to the control. Additional, the embryonic toxicity and growth inhibition were also determined in the fish larvae. Overall, this study examined the impacts of parental co-exposure to Cd and TBT, with regard to developmental inhibition, nervous system damage and endocrine disruption, which highlighted that co-exposure influences are complicated and need to be considered for accurate environmental risk assessment.
Afficher plus [+] Moins [-]A multi-omics approach reveals molecular mechanisms by which phthalates induce cardiac defects in zebrafish (Danio rerio)
2020
Mu, Xiyan | Chen, Xiaofeng | Liu, Jia | Yuan, Lilai | Wang, Donghui | Qian, Le | Qian, Yu | Shen, Gongming | Huang, Ying | Li, Xuxing | Li, Yingren | Lin, Xiangming
The potential risks of phthalates affecting human and animal health as well as the environment are emerging as serious concerns worldwide. However, the mechanism by which phthalates induce developmental effects is under debate. Herein, we found that embryonic exposure of zebrafish to di-(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) increased the rate of heart defects including abnormal heart rate and pericardial edema. Changes in the transcriptional profile demonstrated that genes involved in the development of the heart, such as tbx5b, nppa, ctnt, my17, cmlc1, were significantly altered by DEHP and DBP at 50 μg/L, which agreed with the abnormal cardiac outcomes. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) further showed that significant hypomethylation of nppa and ctnt was identified after DEHP and DBP exposure, which was consistent with the up-regulation of these genes. Notably, hypermethylation on the promoter region (<1 kb) of tbx5b was found after DEHP and DBP exposure, which might be responsible for its decrease in transcription. In conclusion, phthalates have the potential to induce cardiac birth defects, which might be associated with the transcriptional regulation of the involved developmental factors such as tbx5b. These findings would contribute to understand the molecular pathways that mediated the cardiac defects caused by phthalates.
Afficher plus [+] Moins [-]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.
Afficher plus [+] Moins [-]Active emigration from climate change-caused seawater intrusion into freshwater habitats
2020
Venâncio, C. | Ribeiro, R. | Lopes, I.
Ecological risk assessment associated with seawater intrusions has been supported on the determination of lethal/sublethal effects following standard protocols that force exposure neglecting the ability of mobile organisms to spatially avoid salinized environments. Thus, this work aimed at assessing active emigration from climate change-caused seawater intrusion into freshwater habitats. To specific objectives were delineated: first, to compute median 12-h avoidance conductivities (AC₅₀,₁₂ₕ) for freshwater species, and second, to compare it with literature data (LC₅₀,₄₈ ₒᵣ ₉₆ₕ, EC₅₀,₆ ₒᵣ ₂₁d) to assess the relevance of the inclusion of stressor-driven emigration into risk assessment frameworks. Four standard test species, representing a broad range of ecological niches – Daphnia magna, Heterocypris incongruens, Danio rerio and Xenopus laevis – were selected. The salt NaCl was used as a surrogate of natural seawater to create the saline gradient, which was established in a 7-compartment system.At each specific LC₅₀, ₄₈ ₒᵣ ₉₆ₕ, the proportion of avoiders were well above 50%, ranging from 71 to 94%. At each LC₅₀, considering also avoiders, populations would decline by 85–97%. Furthermore, for D. magna and X. laevis it was noticed that at the lowest conductivities eliciting mortality, the avoidance already exceeded 50%.The results showed that the emigration from salinity-disturbed habitats exists and that can even be more sensitive than standard endpoints. Looking solely to standard endpoints involving forced exposure may greatly underestimate the risk of local population extinction, because habitat function can be severely disrupted, with subsequent stressor-driven emigration, before any adverse physiological effects at the organism level. Thus, the present study highlights the need to include non-forced exposure testing into ecological risk assessment, namely of salinity-menaced costal freshwaters.
Afficher plus [+] Moins [-]Influence of humic acid on arsenic bioaccumulation and biotransformation to zebrafish: A comparative study between As(III) and As(V) exposure
2020
Wang, Xiaoyan | Liu, Liping | Wang, Xiangrui | Ren, Jinqian | Jia, Pei | Fan, Wenhong
Previous studies have indicated that natural organic matter in the aquatic environment could affect arsenic bioaccumulation and biotransformation to aquatic organisms. However, the differences between the effects of arsenite and arsenate exposure have not been studied and compared in fish exposure models. In this study, adult zebrafish (Danio rerio) were exposed to 5 mg/L inorganic As solutions, in the presence of a range of humic acid (HA) concentrations (1, 2.5, 5, 10, 20 mg/L) in 96 h waterborne exposure. Results showed that in the presence of HA, total As bioaccumulation was significantly reduced in zebrafish following arsenite exposure, while this reduction was not observed during arsenate exposure. The reduction in total arsenic bioaccumulation for arsenite exposure can be explained by the fact that HA forming a surface coating on the cell surface, hindering transport and internalization. However, this reduction in total As was not observed due to differences in uptake pathways for arsenate exposure. Results also showed that Arsenobetaine (AsB) was the main biotransformation product in zebrafish following inorganic As exposure, accounting for 44.8%–64.7% of extracted arsenic species in all exposure groups. The addition of HA caused levels of MMA and As(III) to decrease, while the distribution of AsB significantly increased in arsenite exposure groups. The increase in AsB could be because the As(III)-HA complex was formed, affecting the methylation of As(III). In contrast, the addition of HA to arsenate exposure groups, did not affect the reduction of As(V) to As(III) and therefore, an increase in the distribution of AsB was not observed in arsenate exposure groups. This study provides useful information on the mechanisms of toxicity, for improved risk assessment of As in natural aquatic environments.
Afficher plus [+] Moins [-]Dietary administration of probiotic Lactobacillus rhamnosus modulates the neurological toxicities of perfluorobutanesulfonate in zebrafish
2020
Liu, Mengyuan | Song, Shiwen | Hu, Chenyan | Tang, Lizhu | Lam, James C.W. | Lam, Paul K.S. | Chen, Lianguo
Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb the neural signaling along gut-brain axis, whereas probiotic additives have been applied to improve neuroendocrine function of teleosts. Both PFBS and probiotics can commonly target nervous system. However, whether and how probiotic bacteria can modulate the neurotoxicities of PFBS remain not explored. It is thus necessary to elucidate the probiotic modulation of PFBS neurotoxicity, which can provide implications to the application of probiotic bacteria in aquaculture industry. In the present study, adult zebrafish were exposed to 0, 10 and 100 μg/L PFBS with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic along gut-brain axis was examined, covering three dominant pathways (i.e., neurotransmission, immune response and hypothalamic-pituitary-adrenal (HPA) axis). The results showed that, compared to the single effects, PFBS and probiotic coexposure significantly altered the acetylcholinesterase activity and neurotransmitter profiles in gut and brain of zebrafish, with mild effects on neuronal integrity. Neurotransmitters closely correlated reciprocally in intestines, which, however, was distinct from the correlation profile in brains. In addition, PFBS and probiotic were combined to impact brain health through absorption of bacterial lipopolysaccharides and production of inflammatory cytokines. Relative to neurotransmission and immune signaling, HPA axis was not involved in the neurotoxicological interaction between PFBS and probiotic. Furthermore, it needs to point out that interactive modes between PFBS and probiotic varied a lot, depending on exposure concentrations, sex and toxic indices. Overall, the present study provided the first evidence that probiotic supplement could dynamically modulate the neurotoxicities of PFBS in teleost.
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