CdSe Quantum Dot (QD)-Induced Morphological and Functional Impairments to Liver in Mice

Liu, Wei; Zhang, Shuping; Wang, Lixin; Qu, Chen; Zhang, Chang-wen; Lei, Hong; Lin, Yuan; Huang, Zehao; Wang, Zhe; Liu, Sijin; Jiang, Guibin

doi:10.1371/journal.pone.0024406

Cited by 63 publications

(72 citation statements)

References 36 publications

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“…Organisms that escaped clearance in the liver were found in other tissues, including spleen, bone marrow, and lungs (Gregory et al, 2002). Liver has been demonstrated to be the preferential organ for clearance of Quantum dots as well (Liu et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Development of a fluorescence-basedin vivophagocytosis assay to measure mononuclear phagocyte system function in the rat

Tartaro

Vanvolkenburg

Wilkie

et al. 2014

Journal of Immunotoxicology

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The mononuclear phagocyte system (MPS) which provides protection against infection is made up of phagocytic cells that engulf and digest bacteria or other foreign substances. Suppression of the MPS may lead to decreased clearance of pathogenic microbes. Drug delivery systems and immunomodulatory therapeutics that target phagocytes have a potential to inhibit MPS function. Available methods to measure inhibition of MPS function use uptake of radioactivelylabeled cells or labor-intensive semi-quantitative histologic techniques. The objective of this work was to develop a non-radioactive quantitative method to measure MPS function in vivo by administering heat-killed E. coli conjugated to a pH-sensitive fluorescent dye (Bioparticles Õ ). Fluorescence of the BioparticlesÕ is increased at low pH when they are in phagocytic lysosomes. The amount of Bioparticles Õ phagocytosed by MPS organs in rats was determined by measuring fluorescence intensity in livers and spleens ex vivo using an IVIS Õ Spectrum Preclinical In Vivo Imaging System. Phagocytosis of the particles by peripheral blood neutrophils was measured by flow cytometry. To assess method sensitivity, compounds likely to suppress the MPS [clodronate-containing liposomes, carboxylate-modified latex particles, maleic vinyl ether (MVE) polymer] were administered to rats prior to injection of the Bioparticles Õ . The E. coli particles consistently co-localized with macrophage markers in the liver but not in the spleen. All of the compounds tested decreased phagocytosis in the liver, but had no consistent effects on phagocytic activity in the spleen. In addition, administration of clodronate liposomes and MVE polymer increased the percentage of peripheral blood neutrophils that phagocytosed the Bioparticles Õ . In conclusion, an in vivo rat model was developed that measures phagocytosis of E. coli particles in the liver and may be used to assess the impact of test compounds on MPS function. Still, the detection of inhibition of splenic macrophage function will require further assay development.

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Section: Discussionmentioning

confidence: 99%

Development of a fluorescence-basedin vivophagocytosis assay to measure mononuclear phagocyte system function in the rat

Tartaro

Vanvolkenburg

Wilkie

et al. 2014

Journal of Immunotoxicology

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“…The human hepatocellular carcinoma cell line, HepG2, and the mouse hepatocellular carcinoma cell line, Hepa 1-6, obtained from the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences were cultured in RPMI-1640 and Dulbecco's modified Eagle's medium (DMEM), respectively, supplemented with 10% heat-inactivated fetal bovine serum (FBS) (all from Gibco, Grand Island, NY, USA) at 37˚C under a humidified atmosphere with 5% CO 2 , as previously described (22,23). The cells were collected for RNA or protein extraction 24 h after being subjected to the various treatments (the cells were treated with the various compounds at concentrations of 5 µM for 24 h).…”

Section: Chemicalsmentioning

confidence: 99%

Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling

Zhang

Liu

Guo

et al. 2016

International Journal of Molecular Medicine

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Abstract. Systemic iron homeostasis is strictly controlled under normal conditions to ensure a balance between the absorption, utilization, storage and recycling of iron. The hepcidin-ferroportin (FPN) axis is of critical importance in the maintenance of iron homeostasis. Hepcidin deficiency gives rise to enhanced dietary iron absorption, as well as to increased iron release from macrophages, and this in turn results in iron accumulation in the plasma and organs, and is associated with a range of tissue pathologies. Low hepcidin levels have been demonstrated in most forms of hereditary hemochromatosis (HH), as well as in β-thalassemia. Therapies that increase hepcidin concentrations may potentially play a role in the treatment of these iron overload-related diseases. To date, natural compounds have not been extensively investigated for this purpose, to the best of our knowledge. Thus, in the present study, we screened natural compounds that have the potential to regulate hepcidin expression. By performing hepcidin promoter-luciferase assay, RT-qPCR and animal experiments, we demonstrated that icariin and berberine were potent stimulators of hepcidin transcription.Mechanistic experiments indicated that icariin and berberine increased hepcidin expression by activating the signal transducer and activator of transcription 3 (Stat3) and Smad1/5/8 signaling pathways. The induction of hepcidin was confirmed in mice following icariin administration, coupled with associated changes in serum and tissue iron concentrations. In support of these findings, the icariin analogues, epimedin A, B and C, also increased hepatic hepcidin expression. However, these changes were not observed in hepcidin-deficient [Hamp1 -/-or Hamp1-knockout (KO)] mice following icariin administration, thereby verifying hepatic hepcidin as the target of icariin. Although berberine exhibited a robust capacity to promote hepcidin expression in vitro, it failed to alter hepcidin expression in mice. Taken together, the findings of the present study suggest that icariin exhibits a robust capacity to increase hepatic hepcidin expression and to modulate systemic iron homeostasis. The present study therefore highlights the significance of using natural compounds to ameliorate iron disorders through the regulation of hepcidin expression. IntroductionIron is an essential metal involved in a large array of biological processes, such as energy metabolism, DNA replication and other important cellular functions (1-3). Systemic iron homeostasis is accurately and strictly governed to ensure a balance between iron absorption, utilization and storage in mammals (4). Hepcidin is the central hormone secreted by hepatocytes that plays a fundamental role in the regulation of iron flow through limiting dietary iron absorption from the duodenum and reducing iron egress from macrophages (5). Hepcidin achieves this effect by binding to its receptor, ferroportin (FPN; the only known iron exporter thus far), on the plasma membrane of target cells and inducing its internalization ...

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“…Cell experiments were similar to the standard instruction described in our recent publications (Liu et al, 2011;Qu et al, 2012).…”

Section: Cell Culturementioning

confidence: 99%

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

Hou

Zhang

Wang

et al. 2012

Gene

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162

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a b s t r a c t a r t i c l e i n f oIron is essential for the human being, involving in oxygen transport, energy metabolism and DNA synthesis. Iron homeostasis is tightly governed by the hepcidin-ferroportin axis, of which hepcidin is the master regulator. Excess iron is associated with various diseases including osteopenia and osteoporosis, which are closely related to the alternation of the endogenous estrogen level. To verify the biological effect of estrogen on iron metabolism, we established a mouse model of estrogen deficiency by ovariectomy. We demonstrated that the hemoglobin content and serum iron level decreased, whereas the tissue iron level in liver and spleen increased in the ovariectomized mice. Moreover, the transcription of hepatic hepcidin was elevated in ovariectomized mice compared to the control mice. We further demonstrated that there was an estrogen response element (ERE) in the promoter region of the hepcidin gene. The assay using the luciferase reporter system confirmed the existence of a functional ERE in the hepcidin promoter, as the estradiol treatment reduced hepcidin expression in cells transfected with ERE-intact construct, with no response to estradiol in cells transfected with ERE-devoid construct. In conclusion, estrogen greatly contributes to iron homeostasis by regulating hepatic hepcidin expression directly through a functional ERE in the promoter region of hepcidin gene. These findings might help build a better understanding towards the etiology of postmenopausal osteoporosis accompanied by excess tissue iron (such as iron retention of osteoclasts in bone) under estrogen deficiency.

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CdSe Quantum Dot (QD)-Induced Morphological and Functional Impairments to Liver in Mice

Cited by 63 publications

References 36 publications

Development of a fluorescence-basedin vivophagocytosis assay to measure mononuclear phagocyte system function in the rat

Development of a fluorescence-basedin vivophagocytosis assay to measure mononuclear phagocyte system function in the rat

Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

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