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Chronic cereulide exposure causes intestinal inflammation and gut microbiota dysbiosis in mice
2021
Lin, Ruqin | Li, Danyang | Xu, Yangyang | Wei, Mengyao | Chen, Qingmei | Deng, Yiqun | Wen, Jikai
Known as a cause of food poisoning, Bacillus cereus (B. cereus) is widespread in nature. Cereulide, the heat-stable and acid-resistant emetic toxin which is produced by some B. cereus strains, is often associated with foodborne outbreaks, and causes acute emetic toxicity at high dosage exposure. However, the toxicological effect and underlying mechanism caused by chronic low-dose cereulide exposure require to be further addressed. In the study, based on mouse model, cereulide exposure (50 μg/kg body weight) for 28 days induced intestinal inflammation, gut microbiota dysbiosis and food intake reduction. According to the cell models, low dose cereulide exposure disrupted the intestinal barrier function and caused intestinal inflammation, which were resulted from endoplasmic reticulum (ER) stress IRE1/XBP1/CHOP pathway activation to induce cell apoptosis and inflammatory cytokines production. For gut microbiota, cereulide decreased the abundances of Lactobacillus and Oscillospira. Furthermore, cereulide disordered the metabolisms of gut microbiota, which exhibited the inhibitions of butyrate and tryptophan. Interestingly, cereulide exposure also inhibited the tryptophan hydroxylase to produce the serotonin in the gut and brain, which might lead to depression-like food intake reduction. Butyrate supplementation (100 mg/kg body weight) significantly reduced intestinal inflammation and serotonin biosynthesis suppression caused by cereulide in mice. In conclusion, chronic cereulide exposure induced ER stress to cause intestinal inflammation, gut microbiota dysbiosis and serotonin biosynthesis suppression. IRE1 could be the therapeutic target and butyrate supplementation is the potential prevention strategy.
اظهر المزيد [+] اقل [-]Effects of low-dose methylcyclopentadienyl manganese tricarbonyl-derived manganese on the development of diencephalic dopaminergic neurons in zebrafish
2021
Fasano, Giulia | Godoy, Rafael Soares | Angiulli, Elisa | Consalvo, Ada | Franco, Cristina | Mancini, Maria | Santucci, Daniela | Alleva, E. (Enrico) | Ciavardelli, Domenico | Toni, Mattia | Biffali, Elio | Ekker, Marc | Canzoniero, Lorella Maria Teresa | Sordino, Paolo
Fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) is counted as an organic manganese (Mn)-derived compound. The toxic effects of Mn (alone and complexed) on dopaminergic (DA) neurotransmission have been investigated in both cellular and animal models. However, the impact of environmentally relevant Mn exposure on DA neurodevelopment is rather poorly understood. In the present study, the MMT dose of 100 μM (about 5 mg Mn/L) caused up-regulation of DA-related genes in association with cell body swelling and increase in the number of DA neurons of the ventral diencephalon subpopulation DC2. Furthermore, our analysis identified significant brain Mn bioaccumulation and enhancement of total dopamine levels in association with locomotor hyperactivity. Although DA levels were restored at adulthood, we observed a deficit in the acquisition and consolidation of memory. Collectively, these findings suggest that developmental exposure to low-level MMT-derived Mn is responsible for the selective alteration of diencephalic DA neurons and with long-lasting effects on fish explorative behaviour in adulthood.
اظهر المزيد [+] اقل [-]Exposure to wastewater effluent disrupts hypoxia responses in killifish (Fundulus heteroclitus)
2021
Lau, Samantha C. | Mehdi, Hossein | Bragg, Leslie M. | Servos, Mark R. | Balshine, S. (Sigal) | Scott, Graham R.
Hypoxia (low oxygen) often occurs in aquatic ecosystems that receive effluent from municipal wastewater treatment plants (WWTP). The combination of hypoxia and WWTP effluent could impair fish health, because WWTP effluent contains multiple contaminants that could disrupt the physiological pathways fish use to cope with hypoxia, but the interactive effects of these stressors on fish physiology are poorly understood. We have examined this issue by exposing mummichog killifish (Fundulus heteroclitus) to hypoxia (5 and 2 kPa O₂) and/or 100% WWTP effluent for 21 days in a full factorial design. We then measured hypoxia tolerance, whole-animal metabolism, gill morphology, haematology, and tissue metabolites. In clean water, killifish responded to chronic hypoxia with improvements in hypoxia tolerance, as reflected by increases in time to loss of equilibrium at 0.5 kPa (tLOE). These improvements occurred in association with increases in the exposed surface of gill lamellae that resulted from a regression of interlamellar cell mass (ILCM). Concurrent exposure to wastewater attenuated the increases in tLOE and gill remodeling in chronic hypoxia, and nearly depleted brain glycogen stores. Therefore, exposure to WWTP effluent can disrupt the physiological mechanisms fish use to cope with chronic hypoxia and impair hypoxia tolerance. Our research suggests that the combination of stressors near WWTPs can have interactive effects on the physiology and health of fish.
اظهر المزيد [+] اقل [-]Tissue-specific distribution and bioaccumulation of cyclic and linear siloxanes in South Korean crucian carp (carassius carassius)
2021
Wang, Wenting | Cho, Hyeon-Seo | Kim, Kyungtae | Park, Kyunghwa | Oh, Jeong-Eun
The occurrence and distribution of cyclic and linear siloxanes were investigated in South Korean river water and sediment, with a special focus on crucian carp tissues, to evaluate the residual status and potential bioaccumulation of siloxanes. The total siloxanes median concentrations observed in this study were 1495 ng/L in river water, 39.2 ng/g-dry weight [dw] in sediment, and 41.7 ng/g-wet weight [ww] in crucian carp muscle. Cyclic siloxanes (D3–D6) were predominant in all matrices, and D5 (mean: > 81%) was more abundant in biota tissues than in river water (30%) and sediment (26%) samples. Specifically, positive correlations between D5 concentrations and crucian carp sizes (p < 0.01, Spearman) as well as the relatively high estimated biota-sediment accumulation factor value of D5 (D5: 2.31), suggest the high bioaccumulative property of D5 in biota. However, no bioaccumulation potentials were observed for D3, D4, D6, and L3–L17 in this field-scale study. The distributions of major linear siloxanes (L7–L14) in crucian carp gills (17%) and gonads (21%) were higher than in other tissues (brain, 9.6%; liver, 2.6%; muscle, 1.5%). Moreover, relatively high tissue/plasma ratios were observed for linear siloxanes (L7–L10: 1.79–2.12) compared to cyclic siloxanes (D4–D6: 0.829–1.18) (p < 0.01, Mann Whitney U test), which indicated the higher transportability of linear siloxanes to fish tissues than cyclic siloxanes.
اظهر المزيد [+] اقل [-]Size-resolved, quantitative evaluation of the magnetic mineralogy of airborne brake-wear particulate emissions
2021
Gonet, Tomasz | Maher, Barbara A. | Nyirő-Kósa, Ilona | Pósfai, Mihály | Vaculík, Miroslav | Kukutschová, Jana
Exposure to particulate air pollution has been associated with a variety of respiratory, cardiovascular and neurological problems, resulting in increased morbidity and mortality worldwide. Brake-wear emissions are one of the major sources of metal-rich airborne particulate pollution in roadside environments. Of potentially bioreactive metals, Fe (especially in its ferrous form, Fe²⁺) might play a specific role in both neurological and cardiovascular impairments. Here, we collected brake-wear particulate emissions using a full-scale brake dynamometer, and used a combination of magnetic measurements and electron microscopy to make quantitative evaluation of the magnetic composition and particle size of airborne emissions originating from passenger car brake systems. Our results show that the concentrations of Fe-rich magnetic grains in airborne brake-wear emissions are very high (i.e., ~100–10,000 × higher), compared to other types of particulate pollutants produced in most urban environments. From magnetic component analysis, the average magnetite mass concentration in total PM₁₀ of brake emissions is ~20.2 wt% and metallic Fe ~1.6 wt%. Most brake-wear airborne particles (>99 % of particle number concentration) are smaller than 200 nm. Using low-temperature magnetic measurements, we observed a strong superparamagnetic signal (indicative of ultrafine magnetic particles, < ~30 nm) for all of the analysed size fractions of airborne brake-wear particles. Transmission electron microscopy independently shows that even the larger size fractions of airborne brake-wear emissions dominantly comprise agglomerates of ultrafine (<100 nm) particles (UFPs). Such UFPs likely pose a threat to neuronal and cardiovascular health after inhalation and/or ingestion. The observed abundance of ultrafine magnetite particles (estimated to constitute ~7.6 wt% of PM₀.₂) might be especially hazardous to the brain, contributing both to microglial inflammatory action and excess generation of reactive oxygen species.
اظهر المزيد [+] اقل [-]Comparison of the chronic toxicities of graphene and graphene oxide toward adult zebrafish by using biochemical and phenomic approaches
2021
Audira, Gilbert | Lee, Jiann-Shing | Siregar, Petrus | Malhotra, Nemi | Rolden, Marri Jmelou M. | Huang, Jong-Chin | Chen, Kelvin H.-C. | Hsu, Hua-Shu | Hsu, Yuchun | Ger, Tzong-Rong | Hsiao, Chung-Der
Graphene (GR) and graphene oxide (GO) are widely being used as promising candidates for biomedical applications, as well as for bio-sensing, drug delivery, and anticancer therapy. However, their undesirable side effects make it necessary to assess further the toxicity and safety of using these materials. The main objective of the current study was to investigate the toxicities of GR and GO in predicted environmental relevant concentrations in adult zebrafish (Danio rerio), particularly on their behaviors, and conducted biochemical assays to elucidate the possible mechanism that underlies their toxicities. Zebrafish was chronically (∼14 days) exposed to two different doses of GR (0.1 and 0.5 ppm) or GO (0.1 and 1 ppm). At 14 ± 1 days, a battery of behavioral tests was conducted, followed by enzyme-linked immunosorbent assays (ELISA) test on the following day to inspect the alterations in antioxidant activity, oxidative stress, and neurotransmitters in the treated zebrafish brain. An alteration in predator avoidance behavior was observed in all treated groups, while GR-treated fish exhibited abnormal exploratory behavior. Furthermore, altered locomotor activity was displayed by most of the treated groups, except for the high concentration of the GR group. From the ELISA results, we discovered a high concentration of GR exposure significantly decreased several neurotransmitters and cortisol levels. Meanwhile, elevated reactive oxygen species (ROS) were displayed by the group treated with low and high doses of GR and GO, respectively. These significant changes would possibly affect zebrafish behaviors and might suggest the potential toxicity from GR and GO exposures. To sum up, the present study presented new evidence for the effects of GR and GO in zebrafish behavioral dysregulation. We hope these assessments can contribute to our understanding of graphene and graphene oxide biosafety.
اظهر المزيد [+] اقل [-]Triphenyl phosphate delayed pubertal timing and induced decline of ovarian reserve in mice as an estrogen receptor antagonist
2021
Ma, Haojia | Ishida, Keishi | Xu, Chenke | Takahashi, Kyosuke | Li, Yu | Zhang, Chenhao | Kang, Qiyue | Jia, Yingting | Hu, Wenxin | Matsumaru, Daisuke | Nakanishi, Tsuyoshi | Hu, Jianying
Although concerns have been raised about the adverse effects of triphenyl phosphate (TPhP) on female fertility, its risk to ovarian functioning remains unknown. In this study, female C57BL/6 mice at postnatal day 21 were exposed on a daily basis to TPhP dose of 2, 10, and 50 mg/kg for 40 days. A significant delay in pubertal timing was observed in the mice exposed to 50 mg/kg of TPhP. An estrogen-responsive reporter transgenic mice assay demonstrated that TPhP significantly downregulated the estrogen receptor (ER) signaling by 45.1% in the whole body in the 50 mg/kg group, and by 14.7–43.7% in the uterus for all exposure groups compared with the control. This strong antagonistic activity of TPhP toward ER explained the delay in pubertal timing. A significant reduction in the number of follicles in all stages was observed in mice after being exposed to TPhP for 40 days at concentrations of 10 and 50 mg/kg, resulting in a decline of the ovarian reserve. The elevation of the follicle-stimulating hormone concentration may have contributed to this phenomenon, as controlled by the antagonistic activity of TPhP toward ER in the brain. The toxic effects of TPhP on ovarian functioning highlight this chemical as a potential risk factor for female fertility.
اظهر المزيد [+] اقل [-]tmbim4 protects against triclocarban-induced embryonic toxicity in zebrafish by regulating autophagy and apoptosis
2021
Hu, Zhiyong | He, Liting | Wei, Jiajing | Yufang, Su | Wang, Wei | Fan, Zunpan | Xu, Jia | Zhang, Yuan | Wang, Yongfeng | Peng, Meilin | Zhao, Kai | Zhang, Huiping | Liu, Chunyan
Triclocarban (TCC), an antibacterial agent widely used in personal care products, can affect embryonic development. However, the specific molecular mechanism of TCC-induced embryonic developmental damage remains unclear. In this study, TCC exposure was found to increase the expression of tmbim4 gene in zebrafish embryos. The tmbim4 mutant embryos are more susceptible to TCC exposure than wild-type (WT) embryos, with tmbim4 overexpression reducing TCC-induced embryonic death in the former. Exposure of tmbim4 mutant larvae to 400 μg/L TCC substantially increased apoptosis in the hindbrain and eyes. RNA-sequencing of WT and tmbim4 mutant larvae indicated that knockout of the tmbim4 gene in zebrafish affects the autophagy pathway. Abnormalities in autophagy can increase apoptosis and TCC exposure caused abnormal accumulation of autophagosomes in the hindbrain of tmbim4 mutant zebrafish embryos. Pretreatment of TCC-exposed tmbim4 mutant zebrafish embryos with autophagosome formation inhibitors, substantially reduced the mortality of embryos and apoptosis levels. These results indicate that defects in the tmbim4 gene can reduce zebrafish embryo resistance to TCC. Additionally, apoptosis induced by abnormal accumulation of autophagosomes is involved in this process.
اظهر المزيد [+] اقل [-]Plastic smoke aerosol: Nano-sized particle distribution, absorption/fluorescent properties, dysregulation of oxidative processes and synaptic transmission in rat brain nerve terminals
2020
Borysov, Arsenii | Tarasenko, Alla | Krisanova, Natalia | Pozdnyakova, Natalia | Pastukhov, Artem | Dudarenko, Marina | Paliienko, Konstantin | Borisova, Tatiana
Smoke from plastic waste incineration in an open air travels worldwide and is a major source of air pollution particulate matter (PM) that is very withstand to degradation and hazard to human health. Suspension of smoke aerosol components in water occurs during rains and fire extinguishing. Here, water-suspended plastic smoke aerosol (WPS) preparations suitable for biotesting were synthesized. It has been revealed using dynamic light scattering that WPS contained major nano-sized (∼30 nm) PM fraction, and this result was confirmed by electron microscopy. Optical absorption of WPS was in the UV region and an increase in λₑₓ led to a red-shift in fluorescence emission with a corresponding decrease in fluorescence intensity. WPS was analyzed in neurotoxicity studies in vitro using presynaptic rat cortex nerve terminals (synaptosomes). Generation of spontaneous reactive oxygen species (ROS) detected using fluorescent dye 2′,7-dichlorofluorescein in nerve terminals was decreased by WPS (10–50 μg/ml) in a dose-dependent manner. WPS also reduced the H₂O₂-evoked ROS production in synaptosomes, thereby influencing cellular oxidative processes and this effect was similar to that for carbon nanodots. WPS (0.1 mg/ml) decreased the synaptosomal membrane potential and synaptic vesicle acidification in fluorimetric experiments. WPS (1.0 mg/ml) attenuated the synaptosomal transporter-mediated uptake of excitatory and inhibitory neurotransmitters, L-[¹⁴C]glutamate and [³H]GABA, respectively. This can lead to an excessive increase in the glutamate concentration in the synaptic cleft and neurotoxicity via over activation of ionotropic glutamate receptors. Therefore, WPS was neurotoxic and provoked presynaptic malfunction through changes of oxidative activity, reduction of the membrane potential, synaptic vesicle acidification, and transporter-mediated uptake of excitatory and inhibitory neurotransmitters in nerve terminals. In summary, synthesis and emission to the environment of ultrafine PM occur during combustion of plastics, thereby polluting air and water resources, and possibly triggering development of neuropathologies.
اظهر المزيد [+] اقل [-]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.
اظهر المزيد [+] اقل [-]