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AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver
2022
Wang, Huan | Wang, Anqi | Wang, Xinqiao | Zeng, Xiangyin | Xing, Houjuan
The experiment was conducted to investigate the effects of Cadmium (Cd) on growth performance, blood biochemical parameters, oxidative stress, hepatocyte apoptosis and autophagy of weaned piglets. A total of 12 healthy weaned piglets were randomly assigned to the control and the Cd group, which were fed with a basal diet and the basal diet supplemented with 15 ± 0.242 mg/kg CdCl₂ for 30 d, respectively. Our results demonstrated that Cd significantly decreased final body weight, average daily feed intake (ADFI), average daily gain (ADG) and increased feed-to-gain (F/G) ratio (P < 0.05). For blood biochemical parameters, Cd treatment significantly decreased the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), total protein, albumin, copper content and iron content (P < 0.05). In addition, liver injury was observed in the Cd-exposed group. Our results also demonstrated that Cd exposure contributed to the production of ROS, activated the AMPK/PPAR-γ/NF-κB pathway (increasing the expressions of P-AMPK/AMPK, NF-κB, I-κB-β, COX-2, and iNOS, decreasing the expressions of PPAR-γ and I-κB-α), finally induced autophagy (increasing the expressions of Beclin-1, the ratio of LC3-II/LC3-I and p62), and apoptosis (increasing the expressions of Bax, Bak, Caspase-9, and Caspase-3, decreasing the expression of Bcl-2). Overall, these findings revealed the vital role of AMPK/PPAR-γ/NF-κB pathway in Cd-induced liver apoptosis and autophagy, which provided deeper insights into a better understanding of Cd-induced hepatotoxicity.
显示更多 [+] 显示较少 [-]Oxidative stress, metallomics and blood toxicity after subacute low-level lead exposure in Wistar rats: Benchmark dose analyses
2021
Javorac, Dragana | Antonijević, Biljana | Anđelković, Milena | Repić, Aleksandra | Bulat, Petar | Djordjevic, Aleksandra Buha | Baralić, Katarina | Đukić-Ćosić, Danijela | Antonić, Tamara | Bulat, Zorica
Exposure to lead (Pb) is still rising concern worldwide, having in mind that even low-dose exposure can induce various harmful effects. Thus, in-depth knowledge of the targets of Pb toxicity and corresponding mechanisms is essential. In the presented study, the six groups (male Wistar rats, n = 6) received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, each day by oral gavage, while the control group received distilled water only. All animals were sacrificed 24 h after the treatment, and blood was collected for the analysis of hematological, biochemical, oxidative status and essential elements levels. An external and internal dose-response relationship was performed using PROASTweb 70.1 software. The results showed that low doses of Pb affect hematological parameters and lipid profile after 28 days. The possible mechanisms at examined Pb dose levels were a decrease in SOD, O₂•⁻ and Cu and an increase in Zn levels. The dose-dependent nature of changes in cholesterol, HDL cholesterol, O₂.⁻, SOD, AOPP in serum and hemoglobin, Fe, Zn, Cu in blood were obtained in this study. The most sensitive parameters that were alerted are Cu blood levels (BMDL₅: 1.4 ng/kg b.w./day) and SOD activity (BMDL₅: 0.5 μg/kg b.w./day). The presented results provide information that may be useful in further assessing the health risks of low-level Pb exposure.
显示更多 [+] 显示较少 [-]Species-specific transcriptomic responses in Daphnia magna exposed to a bio-plastic production intermediate
2019
Swart, Elmer | de Boer, Tjalf E. | Chen, Guangquan | Vooijs, Riet | van Gestel, Cornelis A.M. | Straalen, N. M. van | Roelofs, Dick
Hydroxymethylfurfural (HMF) is a plant-based chemical building block that could potentially substitute petroleum-based equivalents, yet ecotoxicological data of this compound is currently limited. In this study, the effects of HMF on the reproduction and survival of Daphnia magna were assessed through validated ecotoxicological tests. The mechanism of toxicity was determined by analysis of transcriptomic responses induced by exposure to different concentrations of HMF using RNA sequencing. HMF exerted toxicity to D. magna with an EC₅₀ for effects on reproduction of 17.2 mg/l. HMF exposure affected molecular pathways including sugar and polysaccharide metabolism, lipid metabolism, general stress metabolism and red blood cell metabolism, although most molecular pathways affected by HMF exposure were dose specific. Hemoglobin genes, however, responded in a sensitive and dose-related manner. No induction of genes involved in the xenobiotic metabolism or oxidative stress metabolism pathway could be observed, which contrasted earlier observations on transcriptional responses of the terrestrial model Folsomia candida exposed to the same compound in a similar dose. We found 4189 orthologue genes between D. magna and F. candida, yet only twenty-one genes of those orthologues were co-regulated in both species. The contrasting transcriptional responses to the same compound exposed at a similar dose between D. magna and F. candida indicates limited overlap in stress responses among soil and aquatic invertebrates. The dose-related expression of hemoglobin provides further support for using hemoglobin expression as a biomarker for general stress responses in daphnids.
显示更多 [+] 显示较少 [-]Associations of hemoglobin biomarker levels of acrylamide and all-cause and cardiovascular disease mortality among U.S. adults: National Health and Nutrition Examination Survey 2003–2006
2018
Huang, Mengmeng | Jiao, Jingjing | Wang, Jun | Chen, Xinyu | Zhang, Yu
The potential hazards of acrylamide (AA) have been proposed due to its lifelong exposure. However, the association between AA exposure and mortality remains unclear.We evaluated the prospective association of AA hemoglobin adducts (HbAA and HbGA) with all-cause and cardiovascular disease (CVD) mortality in U.S. population from National Health and Nutrition Examination Survey (NHANES) 2003–2006.We followed 5504 participants who were ≥25 years of age for an average of 6.7 years at the baseline examination with annual linkage to the NHANES statistics database. Using AA hemoglobin biomarkers [HbAA, HbGA, sum of HbAA and HbGA (HbAA + HbGA), and ratio of HbGA to HbAA (HbGA/HbAA)], we determined mortality from all-causes and CVD through Cox proportional hazard regression analysis with multivariable adjustments both in non-smoker group and smoker group. In addition, subgroup analyses and sensitivity analyses were further conducted.After adjusting for sociodemographic, life behavioral and cardiovascular risk factors in non-smoker group, HbAA was positively associated with all-cause mortality (p for trend = 0.0197) and non-CVD mortality (p for trend = 0.0124). HbGA and HbGA/HbAA were inversely associated with all-cause mortality (p for trend = 0.0117 and 0.0098, respectively) and CVD mortality (p for trend=0.0009 and 0.0036, respectively). The multivariable adjusted hazard ratios (HRs) [95% confidence intervals (CIs)] of the upper three quartiles were 0.472 (95% CI: 0.283–0.786), 0.517 (95% CI: 0.299–0.894) and 0.470 (95% CI: 0.288–0.766) between HbGA/HbAA and all-cause mortality comparing with the lowest quartile, respectively. No significant associations were found between HbAA + HbGA and mortality in non-smoker group, and between all AA hemoglobin biomarkers and mortality in smoker group.Hemoglobin biomarker levels of AA were strongly associated with mortality in general U.S. non-smoker adults. These findings proposed a continuous public health concern in relation to environmental and dietary exposure to AA.
显示更多 [+] 显示较少 [-]Hematological and histological changes from ingestion of Deepwater Horizon crude oil in zebra finches (Taeniopygia guttata)
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.
显示更多 [+] 显示较少 [-]Association of acrylamide and glycidamide haemoglobin adduct levels with diabetes mellitus in the general population
2021
Yin, Guangli | Liao, Shengen | Gong, Dexing | Qiu, Hongxia
The frequency and duration of exposure to acrylamide (AA) from the environment and diet are associated with a range of adverse health effects. However, whether long-term AA exposure is related to diabetes mellitus (DM) remains unknown. Data from 3577 adults in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2013–2016 aged ≥ 20 years was analysed. The main analyses applied multivariate logistic regression and restricted cubic spline models to investigate the associations between DM and AA haemoglobin biomarkers, including haemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA to HbAA (HbGA/HbAA) levels. After multivariable adjustment, the odds ratios (95% confidence intervals) for DM comparing the highest with the lowest AA haemoglobin biomarker quartiles were 0.71 (0.55, 0.93), 0.92 (0.71, 1.18), 0.80 (0.62, 1.03) and 1.95 (1.51, 2.51) for HbAA, HbGA, HbAA + HbGA and HbGA/HbAA, respectively. The restricted cubic spline model demonstrated that HbAA was linearly and inversely associated with risk of DM (P for trend = 0.013), while HbGA/HbAA was nonlinearly and positively associated with the prevalence of DM (P for trend <0.001). These results support for epidemiological evidence that the HbAA and HbGA/HbAA are significantly associated with DM. Further studies are warranted to infer the causal role of AA exposure in the prevalence of DM.
显示更多 [+] 显示较少 [-]Multi-biomarkers approach to access the impact of novel metal-insecticide based on flavonoid hesperidin on fish
2021
Bonomo, Marina Marques | Sachi, Ivelise Teresa de Castro | Paulino, Marcelo Gustavo | Fernandes, Joaõ Batista | Carlos, Rose Maria | Fernandes, Marisa Narciso
Aquatic ecosystem health is the main concern to increasing pesticides application to control agricultural pests as it is the ultimate receptor of such materials. This study evaluated the impact of new metal-insecticide, the [Mg(hesp)₂(phen)], referred as MgHP, on fish using physiological, genetic, biochemical, and morphological biomarkers. The fish, Prochilodus lineatus, was exposed to 0 (control), 1, 10, 100, 1000 μg L⁻¹ MgHP, for 24 and 96 h. MgHP was not lethal but caused genotoxicity, altered hematological variables and, the activity of antioxidant and biotransformation enzymes and histology of liver, depending on concentration and time exposure. Hematocrit and erythrocyte number (RBC) increased without change hemoglobin content resulting in changes in hematimetric indexes after 24 h; after 96 h, only RBC was changed. Erythrocyte nuclear abnormalities and crenate cells increased after 24 h but, not after 96 h. Erythrocytes and hepatocytes indicated instability in DNA integrity however, the absence of micronuclei suggested DNA damage repairment. After 24 h, the antioxidant defense system and the phase II biotransformation enzyme was responsiveness and catalase activity decreased at high MgHP concentrations; the antioxidant response was triggered after 96 h. Hepatocyte hypertrophy, intracellular cytoplasmic substances, cytoplasm degeneration, melanomacrophage and hyperemia increased in fish exposed from 10 μg L⁻¹ to higher MgHP concentrations; the organ alteration index increased as MgHP concentration increased showing dose-dependence. Most of hematological and genotoxic effects occurred after 24 h exposure evidencing potential recover capability of organism by activation of the antioxidant defense system and DNA repairment mechanisms. Nevertheless, the histopathological changes in the liver was maintained over time at high MgHP concentrations, a concentration usually no environmental relevant. In conclusion, this data reinforced the importance of continuing research on MgHP effects in other organisms considering the promising use of such compound to control the leaf-cutter ants and other insects.
显示更多 [+] 显示较少 [-]Chronic exposure to MC-LR increases the risks of microcytic anemia: Evidence from human and mice
2021
Pan, Chun | Yan, Minghao | Jin, Haibo | Guo, Hongqian | Han, Xiaodong
Microcystins (MCs) produced by cyanobacteria are potent toxins to humans that cannot be ignored. However, the toxicity of MCs to humans remains largely unknown. The study explored the role of MCs in the development of hematological parameters through human observations and a chronic mouse model to explore related mechanisms. The adjusted odds ratio of MC-LR to the risk of anemia was 4.954 (95 % CI, 2.423–10.131) in a case-control study in Nanjing. An inverse correlation between serum MC-LR and hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and red blood cell count (RBC) was observed. MC-LR in the serum of the population was an independent risk factor for microcytic anemia. Animal experiments demonstrated that MC-LR resulted in microcytic anemia, which is associated with inflammation, dysregulation of iron homeostasis, and erythropoiesis. We first identified the possible signaling pathway of MC-LR-induced anemia that MC-LR significantly upregulated the levels of hepcidin via EPO/EPOR signaling pathway and the decreased levels of Twsg1 and Gdf15, thereby resulting in the decreased levels of Hbb and Fpn, and the increased expression of Fth1, and Tf in a chronic mouse model. Our study first identified that prolonged environmental exposure to MCs probably contribute to the occurrence of microcytic anemia in humans, which provides new insights into the toxicity of MCs for public health.
显示更多 [+] 显示较少 [-]Availability of specific prey types impact pied flycatcher (Ficedula hypoleuca) nestling health in a moderately lead contaminated environment in northern Sweden
2020
Lidman, Johan | Jonsson, Micael | Berglund, Åsa M.M.
Anthropogenic metal contamination can cause increased stress in exposed organisms, but it can be difficult to disentangle the anthropogenic influence from natural variation in environmental conditions. In the proximity of a closed lead (Pb)/zinc (Zn) mine in northern Sweden, the health effects of Pb exposure, essential element (calcium [Ca] and Zn) uptake, and prey availability and composition were estimated on pied flycatcher (Ficedula hypoleuca) nestlings, using hemoglobin (Hb) level as a proxy for health. Pb concentration in nestling blood range between 0.00034 and 2.21 μg/g (ww) and nestlings close to the mine had higher Pb concentrations and lower Hb, but contrary to our hypothesis, Hb was not directly related to Pb accumulation. Proportions of flying terrestrial and aquatic insects in available prey and availability of flying terrestrial insects were positively associated with nestling Hb, whereas the proportion of terrestrial ground living prey, the most common prey type, showed a negative association. This suggests that positive influence of certain prey, which does not have to be the most common in the surroundings, can counteract the negative effects from Pb contamination on bird health. Nestlings inhabiting sites adjacent to lakes had an advantage in terms of prey composition and availability of preferred prey, which resulted in higher Hb. As such, our results show that during moderate exposure to metals, variation in natural conditions, such as prey availability, can have great impact on organism health compared to Pb exposure.
显示更多 [+] 显示较少 [-]Repeated measures of prenatal phthalate exposure and maternal hemoglobin concentration trends: The Ma'anshan birth cohort (MABC) study
2018
Zhu, Yuan-duo | Zhu, Bei-bei | Gao, Hui | Huang, Kun | Xu, Yuan-yuan | Yan, Shuang-qin | Zhou, Shan-shan | Cai, Xiu-xiu | Zhang, Qiu-feng | Qi, Juan | Jin, Zhong-xiu | Sheng, Jie | Pan, Wei-jun | Hao, Jia-hu | Zhu, Peng | Tao, Fang-biao
A prospective cohort study of a Chinese population was conducted to investigate the relationship between prenatal phthalates exposure and maternal hemoglobin or anemia. Based on the Ma'anshan Birth Cohort study, 7 phthalate metabolites were quantified in spot pregnancy urine samples (n = 9263) from 3269 pregnant women during each trimester. The maternal hemoglobin concentrations were obtained from electronic medical records at the same three time points for each participant during pregnancy. Anemia was defined as a hemoglobin concentration below 110 g/L in pregnant women. Repeated measures and trimester-specific analyses were used to estimate the effects of phthalates exposure on maternal hemoglobin and anemia. The prevalence of anemia was 3.6%, 27.0%, and 26.5% during the first, second and third trimester, respectively. Repeated measures analysis showed that hemoglobin concentrations decreased by 0.55, 0.19, 0.57, 0.49, and 0.54 g/L with each 1 ln-transformed concentration increase of MBP, MBzP, MEHP, MEOHP, and MEHHP, respectively. Exposure to MMP, MBP, MEHP, MEOHP, and MEHHP increased the risk of anemia by 1.11-fold, 1.21-fold, 1.20-fold, 1.13-fold, and 1.16-fold, respectively. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. This is the first study focusing on the effect of prenatal phthalate exposures on hemoglobin or anemia in pregnant Chinese women. We found that prenatal phthalates exposure not only decreased the concentrations of hemoglobin but also showed associations with the prevalence of anemia. Associations appeared stronger for the subsample representing women pregnant with a male fetus than those pregnant with a female fetus. Anemia remains a moderate public health problem in China, and effective measures should be implemented.
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