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Gamma-irradiation fluctuates the mRNA N6-methyladenosine (m6A) spectrum of bone marrow in hematopoietic injury Полный текст
2021
Zhang, Shuqin | Dong, Jiali | Li, Yuan | Xiao, Huiwen | Shang, Yue | Wang, Bin | Chen, Zhiyuan | Zhang, Mengran | Fan, Saijun | Cui, Ming
Humans benefit from nuclear technologies but consequently experience nuclear disasters or side effects of iatrogenic radiation. Hematopoietic system injury first arises upon radiation exposure. As an intricate new layer of genetic control, the posttranscriptional m⁶A modification of RNA has recently come under investigation and has been demonstrated to play pivotal roles in multiple physiological and pathological processes. However, how the m⁶A methylome functions in the hematopoietic system after irradiation remains ambiguous. Here, we uncovered the time-varying epitranscriptome-wide m⁶A methylome and transcriptome alterations in γ-ray-exposed mouse bone marrow. 4 Gy γ-irradiation rapidly (5 min and 2 h) and severely impaired the mouse hematopoietic system, including spleen and thymus weight, blood components, tissue inflammation and malondialdehyde (MDA) levels. The m⁶A content and expression of m⁶A related enzymes were altered. Gamma-irradiation triggered dynamic and reversible m⁶A modification profiles and altered mRNA expression, where both m⁶A fold-enrichment and mRNA expression most followed the (5 min_up/2 h_down) pattern. The CDS enrichment region preferentially upregulated m⁶A peaks at 5 min. Moreover, the main GO and KEGG pathways were closely related to metabolism and the classical radiation response. Finally, m⁶A modifications correlated with transcriptional regulation of genes in multiple aspects. Blocking the expression of m⁶A demethylases FTO and ALKBH5 mitigated radiation hematopoietic toxicity. Together, our findings present the comprehensive landscape of mRNA m⁶A methylation in the mouse hematopoietic system in response to γ-irradiation, shedding light on the significance of m⁶A modifications in mammalian radiobiology. Regulation of the epitranscriptome may be exploited as a strategy against radiation damage.
Показать больше [+] Меньше [-]Hematological and histological changes from ingestion of Deepwater Horizon crude oil in zebra finches (Taeniopygia guttata) Полный текст
2021
Fallon, Jesse A. | Goodchild, Christopher | DuRant, Sarah E. | Cecere, Thomas | Sponenberg, D Phillip | Hopkins, William A.
Exposure to crude oil during spill events causes a variety of pathologic effects in birds, including oxidative injury to erythrocytes, which is characterized in some species by the formation of Heinz bodies and subsequent anemia. However, not all species appear to develop Heinz bodies or anemia when exposed to oil, and there are limited controlled experiments that use both light and electron microscopy to evaluate structural changes within erythrocytes following oil exposure. In this study, we orally dosed zebra finches (Taeniopygia guttata) with 3.3 or 10 mL/kg of artificially weathered Deepwater Horizon crude oil or 10 mL/kg of peanut oil (vehicle control) daily for 15 days. We found that birds receiving the highest dosage experienced a significant increase in reticulocyte percentage, mean corpuscular hemoglobin concentration, and liver mass, as well as inflammation of the gastrointestinal tract and lymphocyte proliferation in the spleen. However, we found no evidence of Heinz body formation based on both light and transmission electron microscopy. Although there was a tendency for packed cell volume and hemoglobin to decrease in birds from the high dose group compared to control and low dose groups, the changes were not statistically significant. Our results indicate that additional experimental dosing studies are needed to understand factors (e.g., dose- and species-specific sensitivity) and confounding variables (e.g., dispersants) that contribute to the presence and severity of anemia resulting from oil exposure in birds.
Показать больше [+] Меньше [-]Effects of two little-studied environmental pollutants on early development in anurans Полный текст
2020
Bókony, Veronika | Verebélyi, Viktória | Ujhegyi, Nikolett | Mikó, Zsanett | Nemesházi, Edina | Szederkényi, Márk | Orf, Stephanie | Vitányi, Evelin | Móricz, Ágnes M.
Despite intensive ecotoxicological research, we still know relatively little about the ecological impacts of many environmental contaminants. Filling these knowledge gaps is particularly important regarding amphibians, because they play significant roles in freshwater and terrestrial ecosystems, and their populations are declining worldwide. In this study, we investigated two pollutants that have been poorly studied in ecotoxicology despite their widespread occurrence in surface waters: the herbicide terbuthylazine and the pharmaceutical drug carbamazepine. We exposed two anuran species throughout their larval development to each of two environmentally relevant concentrations of each pollutant, and recorded mortality and 17 sub-lethal endpoints up to several months after exposure. Mortality was low and unrelated to treatment. In agile frogs (Rana dalmatina), we found that treatment with 0.3 μg/L terbuthylazine decreased tadpole activity and reduced fat bodies in juveniles, whereas treatment with 50 μg/L carbamazepine decreased spleen size and increased spleen pigmentation. In common toads (Bufo bufo), treatment with 0.003 μg/L terbuthylazine increased body mass at metamorphosis, treatment with 0.3 μg/L terbuthylazine increased the size of optic tecta, and treatment with 0.5 μg/L carbamazepine decreased hypothalamus size. Treatment with 50 μg/L carbamazepine reduced the feeding activity of toad tadpoles, decreased their production of anti-predatory bufadienolide toxins, and increased their body mass at metamorphosis; juvenile toads in this treatment group had reduced spleen pigmentation. Neither treatments affected the time to metamorphosis, post-metamorphic body mass, or sex ratios significantly. These results show that environmental levels of both terbuthylazine and carbamazepine can have several sub-lethal effects on anurans, which may be detrimental to individual fitness and population persistence in natural conditions. Our findings further highlight that toxic effects cannot be generalized between chemicals of similar structure, because the terbuthylazine effects we found do not conform with previously reported effects of atrazine, a related and extensively studied herbicide.
Показать больше [+] Меньше [-]Muscle melanisation of southern sand flathead (Platycephalus bassensis) in the Tamar Estuary, Tasmania, Australia Полный текст
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.
Показать больше [+] Меньше [-]Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species Полный текст
2017
Mercury (Hg) exposure poses a threat to both fish and human health. Sharks are known to bioaccumulate Hg, however, little is known regarding how Hg is distributed between different tissue groups (e.g. muscle regions, organs). Here we evaluated total mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two different shark species, bonnethead (Sphyrna tiburo) and silky shark (Carcharhinus falciformis) to determine the relationships of THg concentrations between and within tissue groups. Total Hg concentrations were highest in the eight muscle regions with no significant differences in THg concentrations between the different muscle regions and muscle types (red and white). Results from tissue collected from any muscle region would be representative of all muscle sample locations. Total Hg concentrations were lowest in samples taken from the fin inner core of the first dorsal, pectoral, and caudal (lower lobe) fins. Mercury concentrations for samples taken from the trailing margin of the dorsal, pectoral, and caudal fins (upper and lower lobe) were also not significantly different from each other for both species. Significant relationships were found between THg concentrations in dorsal axial muscle tissue and the fin inner core, liver, kidney, spleen and heart for both species as well as the THg concentrations between the dorsal fin trailing margin and the heart for the silky shark and all other sampled tissue types for the bonnethead shark. Our results suggest that biopsy sampling of dorsal muscle can provide data that can effectively estimate THg concentrations in specific organs without using more invasive, or lethal methods.
Показать больше [+] Меньше [-]Native Prussian carp (Carassius gibelio) health status, biochemical and histological responses to treated wastewaters Полный текст
2016
Topić Popović, Natalija | Strunjak-Perović, Ivančica | Barišić, Josip | Kepec, Slavko | Jadan, Margita | Beer-Ljubić, Blanka | Matijatko, Vesna | Palić, Dušan | Klobučar, Goran | Babić, Sanja | Gajdoš Kljusurić, Jasenka | Čož-Rakovac, Rozelindra
The aim of this study was to assess the impact of treated wastewaters on native wild Prussian carp inhabiting effluent-receiving waters (ERC) receiving municipal and sugar plant treated wastewaters, further downstream waters (DW), and a detached canal unaffected by the WWTP activities. To that end, general fish health status was determined, including plasma biochemical, haematological, oxidative stress and tissue histopathological indices, over three seasons. The greatest tissue alterations were in fall in ERC during sugar beet processing, as hypertrophy of gill epithelial and interlamellar cells, necrosis and lymphocytic infiltration, hyperplasia and hypertrophy of renal tubules, distention of hepatic sinusoids. In fall the lowest leukocytes, lymphocytes and granulocytes (2467 ± 565, 1333 ± 264, 1133 ± 488 cells/μL respectively), as well as highest plasma ALP (52.7 ± 19.39 U/L) were measured. ERC in fall had the highest ammonium (20 mg/L), nitrite (1.48 mg/L), nitrate (13.4 mg/L), and lowest dissolved O2 (1.23 mg/L). Gill, kidney and liver alterations, and the highest plasma cholesterol (9.1 ± 1.98 mmol/L) were noted in DW fish in fall. Tissue morphology during sugar cane processing seems a consequence of cellular and structural tissue integrity loss. Structural heterogeneity of gills and spleen was enhanced with increasing concentrations of heavy metals and correlated with oxidative stress (SOD 392.5 ± 77.28 U/L). Monogenean infestation was moderate in ERC fish in all seasons compared with DW fish. Prussian carp biological responses to multiple stressors, measured by the effects of WWTP on blood and tissue parameters, reached far downstream and were not of localized nature. This study demonstrated that in aquatic environments impacted with complex contaminants acting synergistically, causal relationships between biological responses and environmental stressors should be interpreted. Integrated histopathological, haematological and biochemical findings are valuable biomarkers for native fish adaptive patterns and monitoring of water quality/pollution of freshwater ecosystems.
Показать больше [+] Меньше [-]Hydroquinone exposure alters the morphology of lymphoid organs in vaccinated C57Bl/6 mice Полный текст
2020
Fabris, André Luis | Nunes, Andre Vinicius | Schuch, Viviane | de Paula-Silva, Marina | Rocha, GHO | Nakaya, Helder I. | Ho, Paulo Lee | Silveira, Eduardo L.V. | Farsky, Sandra Helena Poliselli
The influenza is a common viral infection that can be fatal, especially in high-risk groups such as children, pregnant women, elderly, and immune-deficient individuals. Vaccination is the most efficient approach to prevent the spreading of viral infection and promote individual and public health. In contrast, exposure to environmental pollutants such as cigarette smoke reduces the efficacy of vaccination. We investigated whether chronic exposure to hydroquinone (HQ), the most abundant compound of the tobacco particulate phase, could impair the adaptive immune responses elicited by influenza vaccination. For this, adult male C57BL/6 mice were daily exposed to either nebulized HQ or PBS for 1 h for a total of eight weeks. At weeks 6 and 8, the mice were primed and boosted with the trivalent influenza vaccine via IM respectively. Although the HQ exposure did not alter the body weight of the mice and the biochemical and hematological parameters, the pollutant increased the oxidative stress in splenocytes of immunized animals, modified the morphology of spleen follicles, and augmented the size of their lymph nodes. The lymphoid organs of HQ-exposed mice presented a similar number of vaccine-specific IgG-secreting cells, titers of vaccine-specific total IgG, and respective subclasses. Transcriptome studies with HQ, benzene, or cigarette smoke exposure were also analyzed. The genes up-regulated upon pollutant exposure were associated with neutrophil migration and were shown to be co-expressed with antibody-secreting cell genes. Therefore, these findings suggest that HQ exposure may trigger an immune-compensatory mechanism that enhances the humoral responses induced by influenza vaccination.
Показать больше [+] Меньше [-]Weathered Mississippi Canyon 252 crude oil ingestion alters cytokine signaling, lowers heterophil:lymphocyte ratio, and induces sickness behavior in zebra finches (Taeniopygia guttata) Полный текст
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.
Показать больше [+] Меньше [-]Excretion characteristics and tissue accumulation of tetrabromobisphenol-A in male rats after sub-chronic inhalation exposure Полный текст
2020
Yu, Yun jiang | Chen, Xi chao | Wang, Zheng-Dong | Liu, Liting | Ge, Qing zhi | Wang, Qiong | Zhang, Yan ping | Yu, Zi ling | Ma, Rui xue
Tetrabromobisphenol-A (TBBPA) is an emerging organic pollutant and a commonly used brominated flame retardant that has received much attention owing to its toxicity. Although TBBPA is ubiquitously detected in atmospheric particulate matter and dust, few studies have investigated the sub-chronic inhalation exposure to TBBPA. To further understand the excretion characteristics and tissue accumulation of TBBPA after inhalation exposure, we used the rat model to conduct a sub-chronic inhalation exposure study. Male rats were administered with different doses of aerosol TBBPA (12.9, 54.6, 121.6, and 455.0 mg/m³). TBBPA was found in the excretion (feces and urine) and all the target tissues (lung, liver, heart, thymus gland, spleen, testicles, muscles, kidneys, brain and serum). Feces were the main route of excretion, which contributed 19.18% to 72.54% (urine <0.10%). TBBPA excretion through feces following inhalation administration was much higher than that following oral and dermal exposure, thereby indicating lower bioavailability of TBBPA under inhalation exposure. Liver and serum showed higher levels of TBBPA compared with those of other tissues, thereby suggesting tissue-specific accumulation of TBBPA in rats. Owing to the relative non-invasiveness of serum sampling and greatest TBBPA concentration among the tissues, serum is a suitable matrix for estimation of TBBPA bioaccumulation after inhalation exposure.
Показать больше [+] Меньше [-]Di (2-ethyl hexyl) phthalate (DEHP)-induced spleen toxicity in quail (Coturnix japonica) via disturbing Nrf2-mediated defense response Полный текст
2019
Yu, Lei | Li, Hui-Xin | Guo, Jian-Ying | Huang, Yue-Qiang | Wang, Hui | Talukder, Milton | Li, Jin-Long
Di(2-ethylhexyl) phthalate (DEHP), as a widely used plasticizer, is reported to have widespread environmental and global health hazards. Trace amounts of phthalates in the environment are sufficient to disrupt ecological balance and affect human health. However, DEHP-induced splenic toxicity remains in an unknown state. Therefore, to explore the mechanism of DEHP-induced splenic toxicity, male quail were employed with 0, 250, 500 and 750 mg/kg body weight DEHP by daily gastric perfusion for 45 days. Notably, splenic corpuscular border and cell gap enlargement were observed in the spleen tissue of DEHP-exposed quail under the histopathological analysis. Furthermore, DEHP induced dysregulation of oxidative stress markers by increasing malondialdehyde (MDA) content and decreasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. Low concentration of DEHP (≤250 mg/kg) exposure suppressed nuclear factor-E2-related factor 2 (Nrf2) signaling pathway, while high concentration of DEHP (≥500 mg/kg) exposure activated Nrf2-mediated defense response. DEHP induced splenic oxidative stress via interfering Nrf2 signal pathway and altering the transcription of its downstream genes. In conclusion, this study suggested that DEHP induced splenic toxicity.
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