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Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems
2019
Routti, Heli | Diot, Béatrice | Panti, Cristina | Duale, Nur | Fossi, Maria Cristina | Harju, Mikael | Kovacs, Kit M. | Lydersen, Christian | Scotter, Sophie E. | Villanger, Gro D. | Bourgeon, Sophie
Marine mammals in the Barents Sea region have among the highest levels of contaminants recorded in the Arctic and the Atlantic walrus (Odobenus rosmarus rosmarus) is one of the most contaminated species within this region. We therefore investigated the relationships bewteen blubber concentrations of lipophilic persistent organic pollutants (POPs) and plasma concentrations of perfluoroalkyl substances (PFASs) and markers of endocrine and immune functions in adult male Atlantic walruses (n = 38) from Svalbard, Norway. To do so, we assessed plasma concentrations of five forms of thyroid hormones and transcript levels of genes related to the endocrine and immune systems as endpoints; transcript levels of seven genes in blubber and 23 genes in blood cells were studied. Results indicated that plasma total thyroxine (TT4) concentrations and ratio of TT4 and reverse triiodothyronine decreased with increasing blubber concentrations of lipophilic POPs. Blood cell transcript levels of genes involved in the function of T and B cells (FC like receptors 2 and 5, cytotoxic T-lymphocyte associated protein 4 and protein tyrosine phosphatase non-receptor type 22) were increased with plasma PFAS concentrations. These results suggest that changes in thyroid and immune systems in adult male walruses are linked to current levels of contaminant exposure.
Показать больше [+] Меньше [-]Microcystin-leucine arginine (MC-LR) induces bone loss and impairs bone micro-architecture by modulating host immunity in mice: Implications for bone health
2018
Dar, Hamid Y. | Lone, Yaqoob | Koiri, Raj Kumar | Mishra, Pradyumna K. | Srivastava, Rupesh K.
Osteoporosis or enhanced bone loss is one of the most commonly occurring bone conditions in the world, responsible for higher incidence of fractures leading to increased morbidity and mortality in adults. Bone loss is affected by various environmental factors including diet, age, drugs, toxins etc. Microcystins are toxins produced by cyanobacteria with microcystin-LR being the most abundantly found around the world effecting both human and animal health. The present study demonstrates that MC-LR treatment induces bone loss and impairs both trabecular and cortical bone microarchitecture along with decreasing the mineral density and heterogeneity of bones in mice. This effect of MC-LR was found due to its immunomodulatory effects on the host immune system, wherein MC-LR skews both T cell (CD4+ and CD8+ T cells) and B cell populations in various lymphoid tissues. MC-LR further was found to significantly enhance the levels of osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with simultaneously decreasing the levels of anti-osteoclastogenic cytokines (IL-10 and IFN-γ). Taken together, our study for the first time establishes a direct link between MC-LR intake and enhanced bone loss thereby giving a strong impetus to the naïve field of “osteo-toxicology”, to delineate the effects of various toxins (including cyanotoxins) on bone health.
Показать больше [+] Меньше [-]Atrazine hinders PMA-induced neutrophil extracellular traps in carp via the promotion of apoptosis and inhibition of ROS burst, autophagy and glycolysis
2018
Wang, Shengchen | Zheng, Shufang | Zhang, Qiaojian | Yang, Zijiang | Yin, Kai | Xu, Shiwen
Atrazine (ATR), a selective herbicide, is consistently used worldwide and has been confirmed to be harmful to the health of aquatic organisms. The release of neutrophil extracellular traps (NETs) is one of the newly discovered antimicrobial mechanisms. Although several immune functions have been analyzed under ATR exposure, the effect of ATR on NETs remains mainly unexplored. In the present study, we treated carp neutrophils using 5 μg/ml ATR and 5 μg/ml ATR combined with 100 nM rapamycin to elucidate the underlying mechanisms and to clarify the effect of ATR on phorbol myristate acetate (PMA)-induced NETs. The results of the morphological observation and quantitative analysis of extracellular DNA and myeloperoxidase (MPO) showed that NETs formation were significantly inhibited by ATR exposure. Moreover, we found that in the NETs process, ATR downregulated the expression of the anti-apoptosis gene B-cell lymphoma-2 (Bcl-2), increased the expression of the pro-apoptosis factors Bcl-2-Associated X (BAX), cysteinyl aspartate specific proteinases (Caspase3, 9), and anti-autophagy factor mammalian target of rapamycin (mTOR), decreased the expression of autophagy-related protein light chain 3B (LC3B) and glucose transport proteins (GLUT1, 4), disturbed the activities of phosphofructokinase (PFK), pyruvate kinase (PKM), and hexokinase (HK) and limited reactive oxygen species (ROS) levels, indicating that the reduced NETs release was a consequence of increased apoptosis and diminished ROS burst, autophagy and down-regulated glycolysis under ATR treatment. Meanwhile, rapamycin restored the inhibited autophagy and glycolysis and thus resisted the ATR-suppressed NETs. The present study perfects the mechanism theory of ATR immunotoxicity to fish and has a certain value for human health risk assessment.
Показать больше [+] Меньше [-]Quercetin antagonizes imidacloprid-induced mitochondrial apoptosis through PTEN/PI3K/AKT in grass carp hepatocytes
2021
Miao, Zhiruo | Miao, Zhiying | Wang, Shengchen | Shi, Xu | Xu, Shiwen
Imidacloprid (IMI) is widely used in agriculture, and is toxic to non-target aquatic species. Quercetin (Que) is a flavonoid abundant in fruits and vegetables that exhibits anti-oxidant activity. In the present study, we treated grass carp hepatocytes (L8824) with 0.1 μM Que and/or 1 mM IMI for 24 h to explore the effect of Que on IMI-induced mitochondrial apoptosis. We found that IMI exposure enhanced reactive oxygen species (ROS) generation, inhibiting the activities of SOD, CAT and T-AOC, exacerbating the accumulation of MDA, aggravating the expression of mitochondrial apoptosis pathway (Cyt-C, BAX, Caspase9 and Caspase3) related genes and decreased the expression of anti-apoptosis gene B-cell lymphoma-2 (Bcl-2). In addition, Que and IMI co-treatment significantly restored the activity of anti-oxidant enzymes, downregulated ROS level and apoptosis rate, thereby alleviating the depletion of mitochondrial membrane potential (ΔΨm) and the expression of cytochrome c (Cyt-C), Bcl-2-associated X (BAX), and cysteinyl aspartate specific proteinases (Caspase9 and 3), increasing the Bcl-2 level. Furthermore, we elucidated that Que could inhibit the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), thus activating phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway to attenuate IMI-induced apoptosis. Molecular docking provides assertive evidence for the interaction between Que ligand and PTEN receptor. Consequently, these results indicate that Que effectively antagonizes IMI-induced mitochondrial apoptosis in grass carp hepatocytes via regulating the PTEN/PI3K/AKT pathway.
Показать больше [+] Меньше [-]Environmental exposure to cadmium reduces the primary antibody-mediated response of wood mice (Apodemus sylvaticus) from differentially polluted locations in the Netherlands
2021
García-Mendoza, Diego | van den Berg, Hans J.H.J. | Brink, Nico W. van den
The Wood mouse (Apodemus sylvaticus) is a widespread mammalian species that acts as a reservoir host for multiple infections, including zoonotic diseases. Exposure to immunotoxins, like for instance trace metals, may reduce the ability of the host to mount proper responses to pathogens, potentially increasing the transmission and prevalence of infections. Antibody-mediated responses are crucial in preventing and limiting infections, and the quantification of the primary antibody response is considered a sensitive predictor of immunosuppression. The current study aims to investigate effects of cadmium exposure on the antibody-mediated responses of wood mice inhabiting polluted and non-polluted areas in the Netherlands. Wood mice were captured alive at different locations and immunized to sheep red blood cells (SRBC) to induce a primary antibody response. SRBC-specific antibody-producing cells, or plaque forming cells (PFC), were quantified and related to kidney cadmium levels. Differential circulating main leukocyte populations were also characterised. Cadmium concentrations in mice kidneys differed between mice captured at different locations, and increased with individual body mass, likely associated with age-related time of exposure. Effect of cadmium was apparent on the percentages of B cell counts in blood. Because of potential natural immune heterogeneity between wild rodent populations, mice immune responses were analysed and compared grouped by captured locations. Capture location had significant effect on the total counts of white blood cells. Increasing cadmium exposure in wood mice captured from polluted sites was associated with a decrease of splenic PFC counts. This field research shows that wood mice antibody responses can be impaired by cadmium exposure, even at low environmental levels, by affecting B cell functioning mainly. Impaired B cell function can make exposed mice more susceptible to infections, potentially increasing the reservoir function of their populations. It also shows that immunomodulatory effects in the field should be assessed site specifically.
Показать больше [+] Меньше [-]Bisphenol A and its substitutes regulate human B cell survival via Nrf2 expression
2020
Jang, Ju-Won | Yi, Chae-uk | Yoon, Yeo Dae | Kang, Jong-Soon | Moon, Eun-Yi
B cells contribute to produce inflammatory cytokines and antibodies, to present autoantigens, and to interact with T cells, which lead to body defense and disease control. Nuclear factor (erythroid-derived 2)-like 2(Nrf2) is responsible for gene expression of antioxidant enzymes to protect cells from oxidative stress by reactive oxygen species(ROS) production. Bisphenol A(BPA) may not be safe due to the effect on body’s physiological functions. The chemicals that substitute for BPA may still have similar effects in the body. Tritan™ copolyester is a novel plastic form using BPA substitutes, 1,4-cyclohexanedimethanol(CHDM), dimethyl terephthalate(DMT), and 2,2,4,4-tetramethyl-1,3-cyclobutanediol(TMCD). Isosorbide(ISO) was also used as a substitute for TMCD and DMT. Here, we investigated whether B cell viability is influenced by BPA and its substitutes via Nrf2 induction using WiL2-NS human B lymphoblast cells. When cytotoxicity was measured by using assays with MTT, CellTiter-Glo, trypan blue and propidium iodide, cytotoxicity by BPA was higher than that by substitutes. BPA and its substitutes showed significant cytotoxicity and ROS production, which were attenuated by the treatment with N-acetylcysteine(NAC), a ROS scavenger. In addition, BPA treatment enhanced gene expression of antioxidant enzymes, heme oxygenase(HO)-1, catalase, superoxide dismutase(SOD) 1 and 2. As H₂O₂ treatment induced cell death and Nrf2 amount in WiL2-NS cells, BPA treatment increased Nrf2. Cell death by H₂O₂ was increased in doxycycline-inducible Nrf2-knockdown(KD) cells. In Cytotoxicity by the treatment with BPA or its substitutes was also enhanced in Nrf2-KD cells but that was reduced by Nrf2 overexpression compared to control cells. Taken together, these results implicate that B cell cytotoxicity by substitutes should be lower than BPA and Nrf2 can prevent B cells from BPA- or BPA substitutes-induced cytotoxicity via ROS production. Data suggest that the comprehensive studies or evaluation could be necessary to replace BPA in manufacture by other substitutes.
Показать больше [+] Меньше [-]Immunomodulation and hormonal disruption without compromised disease resistance in perfluorooctanoic acid (PFOA) exposed Japanese quail
2013
Smits, Judit E.G. | Nain, Sukhbir
This study evaluated the impact of oral perfluorooctanoic acid (PFOA) on Japanese quail at concentrations found in American and Belgian workers at PFOA manufacturing facilities. Three arms of the immune system were tested; T cell, B cell, and innate immunity. After 6 weeks exposure, quail were challenged with E. coli infection to test the ultimate measure of immunotoxicity, disease resistance. The T cell response was lower in the high exposure groups. Antibody mediated, and innate immune responses were not different. Growth rate was higher, whereas thyroid hormone levels were lower in PFOA-exposed birds. Morbidity/mortality from disease challenge was not different among the control and PFOA-exposed groups, and no overt PFOA toxicity was observed pre-disease challenge.Although PFOA at ‘worst case scenario’ levels caused T cell immunosuppression, this did not translate into increased disease susceptibility, demonstrating that immunotoxicity testing must be interpreted with caution since disease resistance is the ultimate concern.
Показать больше [+] Меньше [-]LncRNA PTTG3P induced aberrant glycosylated IgA1 production and B cell growth in IgA nephropathy
2021
Bi, Min | Shi, Jie | Zhao, Yu | Li, Chunmei
Growing evidences suggested that lncRNAs played functional role in several cell functions such as cell growth, invasion, migration, metabolize, apoptosis, and differentiation. However, roles of lncRNA in the development and progression of IgAN remain unknown. In this reference, we indicated that PTTG3P level was overexpressed in IgAN samples compared to healthy subject. PTTG3P expression was also higher in urinary of IgAN cases than in urinary of healthy control. Furthermore, the urinary expression of PTTG3P was correlated with PTTG3P expression in intra-renal of IgAN cases. PTTG3P overexpression induced B cell growth and enhanced cyclin D1 and ki-67 expression. Overexpression of PTTG3P induced IL-1β and IL-8 production. miR-383 level was decreased in IgAN samples compared to healthy subject. In addition, miR-383 expression was also lower in urinary of IgAN cases than in urinary of healthy control. Elevated miR-383 expression decreased luciferase intensity regulated with PTTG3P, while overexpression of miR-383 had no effect on luciferase intensity of the mutant PTTG3P. PTTG3P overexpression suppressed miR-383 expression in B cells. Ectopic miR-383 expression suppressed B cell growth and IL-1β and IL-8 production. Finally, we showed that overexpression of PTTG3P promoted B cell growth and IL-1β and IL-8 production via regulating miR-383. There results proved that PTTG3P played crucial role in progression of IgAN.
Показать больше [+] Меньше [-]Cytotoxicity induced by fine particulate matter (PM2.5) via mitochondria-mediated apoptosis pathway in rat alveolar macrophages
2021
Wei, Haiying | Yuan, Wanjun | You, Huan | Geng, Hong
Although positive associations exist between ambient particulate matter (PM₂.₅; diameter ≤ 2.5 μm) and the morbidity and mortality rates for respiratory diseases, the biological mechanisms of the reported health effects are unclear. Considering that alveolar macrophages (AM) are the main cells responsible for phagocytic clearance of xenobiotic particles that reach the airspaces of the lungs, the purpose of this study was to investigate whether PM₂.₅ induced AM apoptosis, and investigate its possible mechanisms. Freshly isolated AM from Wistar rats were treated with extracted PM₂.₅ at concentrations of 33, 100, or 300 μg/mL for 4 h; thereafter, the cytotoxic effects were evaluated. The results demonstrated that PM₂.₅ induced cytotoxicity by decreasing cell viability and increasing lactate dehydrogenase (LDH) levels in AMs. The levels of reactive oxygen species (ROS) and intracellular calcium cations (Ca²⁺) markedly increased in higher PM₂.₅ concentration groups. Additionally, the apoptotic ratio increased, and the apoptosis-related proteins BCL2-associated X (Bax), caspase-3, and caspase-9 were upregulated, whereas B cell lymphoma-2 (Bcl-2) protein levels were downregulated following PM₂.₅ exposure. Cumulative findings showed that PM₂.₅ induced apoptosis in AMs through a mitochondrial-mediated pathway, which indicated that PM₂.₅ plays a significant role in lung injury diseases.
Показать больше [+] Меньше [-]Prophylactic effects of Cynara scolymus L. leaf and flower hydroethanolic extracts against diethylnitrosamine/acetylaminoflourene-induced lung cancer in Wistar rats
2021
Abdel-Moneim, Adel | Ahmed, Osama M. | Abd El-Twab, Sanaa M. | Zaky, Mohamed Y. | Bakry, Lamiaa N.
The study examines the prophylactic action of artichoke leaf hydroethanolic extract (ALE) and artichoke flower head hydroethanolic extract (AFE) against diethylnitrosamine (DEN)/acetylaminofluorene (AAF)-induced lung cancer in Wistar rats. To chemically induce lung cancer, DEN was injected intraperitoneally twice a week for a fortnight at a dose of 150 mg/kg body weight (b.w.), followed by oral supplementation of AAF four times a week for 3 weeks at a dose of 20 mg/kg b.w. The DEN/AAF-administered rats were orally supplemented with ALE or AFE at a dose of 100 mg/kg b.w. for 17 weeks starting from the 1st week of DEN injection to the 17th week of the experiment. The lung cancerous injuries resulting from DEN/AAF-administration were significantly improved by the treatment with ALE and AFE as observed in histological examination. In addition, there was a significant reduction in lung lipid peroxidation, with resultant elevation in antioxidant enzymatic activity of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and superoxide dismutase as well as glutathione content in DEN/AAF-supplemented rats treated with ALE and AFE as compared to DEN/AAF-administered control. The lung tumor suppressor protein (p53) and B-cell lymphoma-2 (Bcl-2) mRNA expression significantly increased in the rats treated with ALE and AFE. In conclusion, the finding showed that ALE and AFE produced anti-cancer prophylactic effects against DEN/AAF-induced lung cancer in rats via suppression of oxidative stress and improved apoptotic signal induction.
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