scholarly journals Combination of ferric ammonium citrate with cytokines involved in apoptosis and insulin secretion of human pancreatic beta cells related to diabetes in thalassemia

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9298
Author(s):  
Patchara Rattanaporn ◽  
Sissades Tongsima ◽  
Thomas Mandrup-Poulsen ◽  
Saovaros Svasti ◽  
Dalina Tanyong
Keyword(s):  
Insulin Secretion ◽  
Cell Viability ◽  
High Glucose ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
High Glucose Condition ◽  
Genes Expression ◽  
Tnf Α ◽  
Ferric Ammonium ◽  
Glucose Condition

Background Diabetes mellitus (DM) is a common complication found in β-thalassemia patients. The mechanism of DM in β-thalassemia patients is still unclear, but it could be from an iron overload and increase of some cytokines, such as interleukin1-β (IL-1β) and tumor necrosis factor-α (TNF-α). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1β and TNF-α, on 1.1B4 human pancreatic β-cell line. Methods The effect of the combination of FAC and cytokines on cell viability was studied by MTT assay. Insulin secretion was assessed by the enzyme-linked immunosorbent assay (ELISA). The reactive oxygen species (ROS) and cell apoptosis in normal and high glucose condition were determined by flow cytometer. In addition, gene expression of apoptosis, antioxidant; glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2), and insulin secretory function were studied by real-time polymerase chain reaction (Real-time PCR). Results The findings revealed that FAC exposure resulted in the decrease of cell viability and insulin-release, and the induction of ROS and apoptosis in pancreatic cells. Interestingly, a combination of FAC and cytokines had an additive effect on SOD2 antioxidants’ genes expression and endoplasmic reticulum (ER) stress. In addition, it reduced the insulin secretion genes expression; insulin (INS), glucose kinase (GCK), protein convertase 1 (PSCK1), and protein convertase 2 (PSCK2). Moreover, the highest ROS and the lowest insulin secretion were found in FAC combined with IL-1β and TNF-α in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in β-thalassemia patients.

ERM Complex, a Therapeutic Target for Vascular Leakage Induced by Diabetes

2021 ◽  
Vol 28 ◽  
Author(s):  
Olga Simó-Servat ◽  
Hugo Ramos ◽  
Patricia Bogdanov ◽  
Marta García-Ramírez ◽  
Jordi Huerta ◽  
...  
Keyword(s):  
High Glucose ◽  
Therapeutic Target ◽  
Vascular Leakage ◽  
Cell Permeability ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Erm Proteins ◽  
High Glucose Condition ◽  
Tnf Α ◽  
Glucose Condition

Background: Ezrin, radixin, and moesin (the ERM complex) interact directly with membrane proteins regulating their attachment to actin filaments. ERM protein activation modifies cytoskeleton organization and alters the endothelial barrier function, thus favoring vascular leakage. However, little is known regarding the role of ERM proteins in diabetic retinopathy (DR). Objective: This study aimed to examine whether overexpression of the ERM complex exists in db/db mice and its main regulating factors. Methods: 9 male db/db mice and 9 male db/+ aged 14 weeks were analyzed. ERM proteins were assessed by western blot and by immunohistochemistry. Vascular leakage was determined by the Evans blue method. To assess ERM regulation, HRECs were cultured in a medium containing 5.5 mM D-glucose (mimicking physiological conditions) and 25 mM D-glucose (mimicking hyperglycemia that occurs in diabetic patients). Moreover, treatment with TNF-α, IL-1β, or VEGF was added to a high glucose condition. The expression of ERM proteins was quantified by RT-PCR. Cell permeability was evaluated by measuring movements of FITC-dextran. Results: A significant increase of ERM in diabetic mice in comparison with non-diabetic mice was observed. A high glucose condition alone did not have any effect on ERM expression. However, TNF-α and IL-1β induced a significant increase in ERM proteins. Conclusion: The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.

Iron overload induced by ferric ammonium citrate triggers reactive oxygen species-mediated apoptosis via both extrinsic and intrinsic pathways in human hepatic cells

2015 ◽  
Vol 35 (6) ◽  
pp. 598-607 ◽  
Author(s):  
S-W Li ◽  
C-M Liu ◽  
J Guo ◽  
AM Marcondes ◽  
J Deeg ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ferric Ammonium

Background: Hepatic iron overload is common in patients with myelodysplastic syndromes undergoing hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better understand the mechanisms of iron overload-induced liver injury, we examined the effects of iron overload induced by ferric ammonium citrate (FAC) on oxidative stress and apoptosis signaling pathway in human hepatic cell line HH4. Methods and Results: Hepatic HH4 cells were exposed to FAC to force iron uptake, and cellular responses were determined. Incubation with 5 mM FAC resulted in increased intracellular iron content in a time-dependent manner. High concentration of FAC impaired cell viability and increased level of reactive oxygen species (ROS), and addition of antioxidant reagent such as glutathione or N-acetylcysteine dramatically reduced FAC-induced intracellular ROS generation. FAC overload significantly increased the phosphorylation of inhibitor of κB-α, p38 mitogen-activated protein kinase (MAPK), and nuclear factor κ light chain enhancer of activated B cells (NF-κB) p65 and promoted the nuclear translocation of NF-κB p65. Knockdown of Fas and Bid expression by small interfering RNA in iron-treated HH4 cells resulted in restoration of cell viability. Conclusions: We reported that FAC treatment is capable of inducing both extrinsic death receptor and intrinsic mitochondrial signaling pathway-mediated HH4 cells apoptosis through ROS-activated p38 MAPK and NF-κB pathways.

scholarly journals Piceatannol-mediated alteration of amyloidogenesis in SH-SY5Y neuroblastoma cells treated with amyloid-beta

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yun Jung Yang ◽  
Hee Yun Cha ◽  
Soo Jin Yang
Keyword(s):  
Amyloid Precursor Protein ◽  
Cell Viability ◽  
Amyloid Beta ◽  
High Glucose ◽  
Neuroblastoma Cells ◽  
Conditioned Media ◽  
Precursor Protein ◽  
High Concentration ◽  
High Glucose Condition ◽  
Glucose Condition

AbstractHigh glucose condition impairs neuronal integrity and function by regulating amyloidogenesis and neuroinflammation. Here, we pursue to investigate whether high glucose condition leads impairments in neuronal integrity/function by inducing amyloidogenesis and neuroinflammation, and whether piceatannol (PIC) restores high glucose condition-induced deteriorations in neuronal cells. High glucose condition was induced by maintaining SH-SY5Y neuroblastoma cells in 25 mM glucose. In addition, amyloid-beta was applied to make the cells having amyloidogenesis-mediated deleterious alterations. Cells were maintained in low glucose (2.5 mM glucose) or high glucose (25 mM glucose) condition. And, two doses (10 and 20 μM) of PIC and/or 10 μM of amyloid-beta were treated in a subset of cells for 24 h. There were no significant differences in cell morphology and cell viability among groups. PIC treatment did not show cell toxicity based on cell viability assessed by PrestoBlue assay. High concentration of glucose and amyloid-beta treatments increased amyloid-beta concentrations in cell lysates and conditioned media, which were reduced by PIC. 10 μM PIC treatment for 24 h decreased amyloid precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme-1, presenilin (PS) 1 and tau. Among analyzed inflammatory markers, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were reduced in conditioned media by 10 μM PIC administration for 24 h. These data indicate that high glucose condition may result in excessive levels of amyloidogenesis and neuroinflammation as well as subsequent changes in neuronal integrity/function, and that PIC treatment may ameliorate the deleterious consequences from high glucose and amyloid-beta treatments.

scholarly journals A study on the aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous fumarate, ferrous sulphate and ferric ammonium citrate, among the rural anaemic women, in the Indian spectrum

2019 ◽  
Vol 8 (12) ◽  
pp. 2751
Author(s):  
Moumita Hazra
Keyword(s):  
Ferrous Sulphate ◽  
Haemoglobin Concentration ◽  
Significant Rise ◽  
Demographic Characteristics ◽  
Health Concern ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Ferrous Fumarate ◽  
Ferrous Ascorbate ◽  
Ferric Ammonium

Background: Anaemia is a global health concern, associated with increased maternal and perinatal mortality, preterm delivery, low birth weight, extreme fatigue and impaired immune system; and controlled by oral haematinics; with a rise in haemoglobin concentration. The objective was to examine the various aspects of pharmacoepidemiology and pharmacohaemovigilance of oral haematinics, among the anaemic women population, in rural India.Methods: This was a multi-centre, retrospective, observational and analytical study of the hospital medical records of 250 anaemic patients, who were allocated into group A of 125 patients within 15-21 years and group B of 125 patients within 22-35 years. The patients were prescribed oral haematinics, containing 60 mg of elemental iron, thrice daily, with meals. The various aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous sulphate, ferrous fumarate and ferric ammonium citrate, including patients’ demographic characteristics, anaemic symptoms assessment, prescription patterns, and safety assessment, on 1st, 2nd, 3rd months and follow-up visits, were recorded and thoroughly analysed..Results: In groups A and B, the demographic characteristics of the patients were comparable; ferrous ascorbate was the most commonly prescribed oral haematinic, followed by ferrous sulphate, ferrous fumarate and ferric ammonium citrate, which controlled mild to moderate iron deficiency anaemia, with a gradual significant rise in haemoglobin concentration, in the successive 3 months; and adverse effects were observed to be statistically non-significant in either group.Conclusions: The different aspects of pharmacoepidemiology and pharmacohaemovigilance in the study established that the oral haematinics were reasonably beneficial and safe among the anaemic women population, in rural India.

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