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High expression of HIF-1α alleviates benzene-induced hematopoietic toxicity and immunosuppression in mice
2022
Huang, Jiawei | Pu, Yunqiu | Xu, Kai | Ding, Qin | Sun, Rongli | Yin, Lihong | Zhang, Juan | Pu, Yuepu
Benzene exposure can cause pancytopenia and immunosuppression, leading to serious diseases such as aplastic anemia (AA) or acute myeloid leukemia (AML), but the underlying mechanism has not been fully elucidated. Hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that regulates many downstream target genes. In this study, we reported a novel mechanism by which high expression of HIF-1α alleviated benzene toxicity. Mice with high expression of HIF-1α (HIF-1α⁺) were obtained by the Tet-on system and doxycycline induction, and they and wild-type (WT) mice were exposed to 150 mg/kg benzene for 0, 1, 3, 7, 10, 14, and 28 days. Dynamic changes in hematopoietic and immune-related indicators and the role of HIF-1α were explored. The level of white blood cells in mice reached the highest level on the third day, and immunity was activated and then suppressed within 10 days. Significant pancytopenia and immunosuppression occurred at 14 days and were more pronounced at 28 days. The levels of HIF-1α, EPO, VEGF, RORγt, and IL-17 in WT mice gradually decreased with increasing benzene exposure days, while the levels of Foxp3 and IL-10 increased. These changes were alleviated in HIF-1α⁺ mice. High expression of HIF-1α increased the levels of EPO and VEGF, which helped to maintain the stability of the hematopoietic microenvironment. Simultaneously, it attenuated benzene-induced immunosuppression by alleviating the Th17/Treg imbalance. HIF-1α is expected to be a new target for benzene-induced diseases such as AA and AML.
Afficher plus [+] Moins [-]Impact of the co-occurrence of obesity with diabetes, anemia, hypertension, and albuminuria on concentrations of selected perfluoroalkyl acids
2020
Jain, Ram B.
Data (N = 10644) for US adults aged ≥20 years for 2003–2016 from National Health and Nutrition Examination Survey were analyzed to evaluate the impact of co-occurrence of obesity with diabetes, anemia, albuminuria, and hypertension on concentrations of five perfluoroalkyl acids (PFAA), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). For the total population, males, and females, co-occurrence of obesity with hypertension, albuminuria, anemia, and diabetes was found to be associated with lower adjusted geometric means (AGM) than nonobese for every PFAA. For example for females, for PFOS, AGMs for obese with no diseases, hypertension, albuminuria, anemia, and diabetes were 8.2, 10.8, 5.8, 4.6, and 7.7 ng/mL respectively. In comparison, for PFOS, for nonobese females, AGMs for those with no diseases, hypertension, albuminuria, anemia, and diabetes were found to be 8.9, 13.4, 7.7, 6.0, and 10.2 ng/mL respectively. This implies obesity is associated with higher excretion rates. Females, in general, had lower AGMs than males for both obese and nonobese for every PFAA for every disease group. For example, percent ratios of obese females to males AGMs for PFOA were 66.7%, 87.1%, 88.2%, 70.6%, and 90% for those with no diseases, hypertension, albuminuria, anemia, and diabetes respectively. The ratios of obese to nonobese AGMs for females were lower than males for every PFAA for those with no diseases and hypertension only. For example, for PFOA for those with no diseases, obese to nonobese AGM ratios were 87% for females and 100% for males. Thus, additional excretion of certain PFAAs due to obesity is higher in females than males for those with no diseases and hypertension only.
Afficher plus [+] Moins [-]Geochemical exposure of heavy metals in environmental samples from the vicinity of old gas mining area in northern part of Sindh Pakistan. Adverse impact on children
2019
Shaikh, Rafia | Kazi, Tasneem Gul | Afridi, Hassan Imran | Akhtar, Asma | Baig, Jameel Ahmed | Arain, Mohammad Balal
In early nineteen century, a gas field was operational in southern part of Sindh, Pakistan for power production. The plant was completely un-operational for last three decades, whereas all wastage and raw materials are still dumped there, which might be the source to contaminate the ground water. The most of the workers population still living in different villages nearby the gas field. In present study, evaluated the undesirable effects of the toxic metals (lead and cadmium) via consuming groundwater for drinking and other domestic purpose especially in children of ≤5.0 years. For comparative purpose groundwater of nonindustrial area (nonexposed) was also analysed and their impact on age matched children was carried out. Biological samples (scalp hair and blood) were collected from children of exposed and nonexposed areas. The Cd and Pb in scalp hair and blood samples were carried out by graphite furnace atomic absorption spectrometry. Whereas, Cd and Pb in groundwater obtained from both areas were determined prior to applied preconcentration method as reported in our previous works. The Cd and Pb contents in the groundwater of villages of exposed area were found in the range of 5.18–10.9 and 19.9–69.5 μg/L, respectively. Whereas, the groundwater of nonexposed area contains Cd and Pb in the range of 1.79–3.78 and 5.07–24.3 μg/L, respectively. It was observed that the concentrations of Cd and Pb in scalp hair and blood samples of children belongs to exposed area have ≥2.0 fold higher than the resulted data attained for age matched control children, indicating as the exposure biomarkers of toxic metals. The children belong to exposed area have poor health, anemic and low body mass index (<13 kg/m2). A significant positive correlations among Cd and Pb concentrations in biological samples of exposed subjects and groundwater was observed (p < 0.01).
Afficher plus [+] Moins [-]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.
Afficher plus [+] Moins [-]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.
Afficher plus [+] Moins [-]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.
Afficher plus [+] Moins [-]Behavior and toxic effects of Pb in a waterfowl model with oral exposure to Pb shots: Investigating Pb exposure in wild birds
2022
Sato, Hiroshi | Ishii, Chihiro | Nakayama, Shouta M.M. | Ichise, Takahiro | Saitō, Keisuke | Watanabe, Yukiko | Ogasawara, Kohei | Torimoto, Ryota | Kobayashi, Atsushi | Kimura, Kei | Johnson, Yuki N. (Yuki Nakamura) | Yamagishi, Junya | Ikenaka, Yoshinori | Ishizuka, Mayumi
Among wild birds, lead (Pb) exposure caused by ingestion of ammunition is a worldwide problem. We aimed to reveal the behavior and toxic effect of Pb caused by ingesting Pb shots in waterfowl. Four male, eight-week old Muscovy ducks (Cairina moschata) were given three Pb shots (approximately 240 mg in total) orally and then fed for 29 days after exposure, simulating a low-dose Pb exposure in wild waterfowl. During the breeding period, blood samples were collected 10 times, and fecal samples every day. Additionally, 22 fresh tissue and 6 bone samples were obtained from each duck through the dissection. Although there were no gross abnormalities, the maximum blood Pb concentration of each duck ranged from 0.6 to 3.7 mg/L, reaching a threshold concentration indicative of clinical symptoms (>0.5 mg/L). δ-aminolevulinic acid dehydratase declined one day after exposure and remained low throughout the feeding period. Hematocrit also tended to decrease, indicating signs of anemia. The highest Pb accumulation was observed in the bones, followed by the kidneys, intestinal tracts, and liver. High Pb accumulation in the bones, which are known to have a long Pb half-life, suggested that Pb would remain in the body and possibly affect bird health beyond 28 days after exposure. Gene expression analysis showed a significant increase in the expression of the toll-like receptor-3 gene, which is involved in virus discrimination in the liver, suggesting a disruption of the immune system. Microbiota analyses showed a correlation between the blood Pb concentration and the abundances of Lachnospiraceae and Ruminococcaceae, suggesting that Pb affects lipid metabolism. These results provide fundamental data on Pb exposure in wild birds and a new perspective on the damage such exposure causes.
Afficher plus [+] Moins [-]Associations between selected perfluoroalkyl acids in serum and hemoglobin in whole blood, a biomarker of anemia: Impact of deteriorating kidney function
2020
Jain, Ram B.
Data (N = 11251) from National Health and Nutrition Examination Survey (NHANES) for 2003–2016 for US adults aged ≥20 years were stratified by gender and anemia and analyzed to evaluate the associations between the concentrations of whole blood hemoglobin (WBHGB) and selected perfluoroalkyl acids (PFAAs) in serum by stages of glomerular filtration (GF). Investigated PFAAs were perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Females with whole blood hemoglobin concentrations <12 g/dL and males with whole blood hemoglobin concentrations <13 g/dL were classified as being anemic. Regression models with log10 transformed concentrations of whole blood hemoglobin as dependent variable and age, poverty income ratio, body mass index, serum cotinine, daily alcohol intake, survey year, and log10 concentrations of one of the PFAA as independent variables were fitted. For anemic females, association between WBHGB and PFAA concentrations were uniformly positive across worsening stages of renal failure and percent increases for 10% increases in PFAAs varied between 0.03% and 0.39%. For anemic males, association between WBHGB and PFAA concentrations were positive except at GF-3A (45 ≤ eGFR<60 mL/min/1.73 m²) and percent increases for 10% increases in PFAAs varied between 0.02% and 0.53%. Thus, more often than not, presence of positive associations between WBHGB and PFAA among anemics imply elevated levels of PFAA are associated with higher levels of WBHGB. Similar results were observed for non-anemic males and females, however strengths of associations between whole blood hemoglobin and PFAAs were several fold higher among anemic compared to non-anemic participants. Hemoglobin is consistently associated with serum PFAAs.
Afficher plus [+] Moins [-]Pb(II) Adsorption on Eastern Spruce Sawdust (Turkey) by Applying Taguchi Method and Adsorption Isotherms
2021
Bilgin, Ayla | Ateş, Esra
Modern industry advances through time with the change in living conditions as more chemicals are used and released into the environment. This causes severe pollution problems, especially of heavy metals including lead (Pb(II)). Pb(II) is continuously released by different industries into the environment, and it leads to certain diseases such as anemia and kidney malfunction. This study examines the adsorption of Pb(II) from aqueous solution regarding eastern spruce sawdust (Picea orientalis) in Turkey, and SEM/EDS and FTIR analyses were applied to determine the chemical structure of Picea orientalis. Moreover, the Taguchi method was utilized to investigate the effects of initial metal ion concentration and contact time on Pb(II) removal. It was found that initial metal concentration has more impact on Pb(II) removal than contact time. The condition of 626 mg/L and 60 min by using 0.3 g sawdust usage was found to be the optimum setting for Pb(II) adsorption. Furthermore, the behavior of Pb(II) adsorption was examined by using Langmuir and Freundlich isotherms. The adsorption occurred not only on the monolayer but also on heterogeneous surfaces due to the R² values close to 1.
Afficher plus [+] Moins [-]Lead exposure in dogs fed game meat and offal from culled invasive species in El Palmar National Park, Argentina
2021
Fernández, Valentina | Caselli, Andrea | Tammone, Agostina | Condorí, Walter Ezequiel | Vanstreels, Ralph Eric Thijl | Delaloye, Aldo | Sosa, Cristian | Uhart, Marcela María
This is the first field study to evaluate lead exposure in dogs fed game meat and offal and, to our knowledge, the first study exploring associations between game consumption and dog health status. We quantified lead concentrations in blood and hair and haematological parameters of 31 dogs fed game meat and offal from wild boar (Sus scrofa) and axis deer (Axis axis) culled with lead ammunition in El Palmar National Park, Argentina. Despite variable weekly frequency in game consumption, dogs had detectable blood and hair lead levels, demonstrating recent and chronic exposure. Lead geometric mean and SD were 18.91 ± 346.85 μg/dL w.w. in blood (range = 0.53–216.58), and 0.721 ± 6.444 μg/gr d.w. in hair (range = 0.007–34.800). Hair lead levels were relatively low in most samples, except for the oldest dog which had an atypically high value concurrent with anaemia, a common outcome of chronic lead exposure. Dog’s owner was significantly predictive of both blood and hair lead levels, which reflects the same feeding patterns for all dogs owned by the same person. Body condition was associated with hair lead, with dogs in good condition presenting higher lead levels. This could be related to greater game consumption by those dogs, resulting in higher lead ingestion. Dogs fed game meat and offal at very low or low frequency (≤4 times per week) showed higher blood lead levels, suggesting there might not be a risk-free frequency for game provision to dogs. Considering the risks of dietary lead exposure, avoiding feeding dogs lead-killed game and replacing lead ammunition with non-toxic alternatives are recommended. This would allow using hunted game as a valuable food resource without unnecessary risk for the health of consumers and the environment.
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