Dataset Information

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

ABSTRACT:

Background

Diabetes mellitus (DM) is a common complication found in ?-thalassemia patients. The mechanism of DM in ?-thalassemia patients is still unclear, but it could be from an iron overload and increase of some cytokines, such as interleukin1-? (IL-1?) and tumor necrosis factor-? (TNF-?). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1? and TNF-?, on 1.1B4 human pancreatic ?-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-1? and TNF-? in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in ?-thalassemia patients.

SUBMITTER: Rattanaporn P

PROVIDER: S-EPMC7304432 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

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

Rattanaporn Patchara P Tongsima Sissades S Mandrup-Poulsen Thomas T Svasti Saovaros S Tanyong Dalina D

PeerJ 20200616

<h4>Background</h4>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.<h4>Methods</h4>The eff ...[more]

PMID: 32587797

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Project description:BackgroundIron deficiency in children can have significant neurological consequences, and iron supplementation is an effective treatment of choice. However, traditional routes of iron supplementation do not allow efficient iron delivery to the brain due to the presence of the blood-brain barrier. So an easily delivered iron formulation with high absorption efficiency potentially could find widespread application in iron deficient infants.ResultsIn this study, we have developed and characterized a nanovesicular formulation of ferric ammonium citrate (ferric ammonium citrate nanoliposomes, FAC-LIP) and have shown that it can increase brain iron levels in rats following nasal administration. FAC was incorporated into liposomes with high efficiency (97%) and the liposomes were small (40 nm) and stable. Following intranasal delivery in rats, FAC-LIP significantly increased the iron content in the olfactory bulb, cerebral cortex, striatum, cerebellum and hippocampus, and was more efficient at doing so than FAC alone. No signs of apoptosis or abnormal cell morphology were observed in the brain following FAC-LIP administration, and there were no significant changes in the levels of SOD and MDA, except in the cerebellum and hippocampus. No obvious morphological changes were observed in lung epithelial cells or tracheal mucosa after nasal delivery, suggesting that the formulation was not overtly toxic.ConclusionsIn this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high encapsulation efficiency and low toxicity in rats. Our studies provide the foundation for more detailed investigations into the applications of niosomal nasal delivery of liposomal formulations of iron as a simple and safe therapy for iron deficiency anemia. Graphical abstract The diagrammatic sketch of "Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain". Nanoliposome-encapsulated ferric ammonium citrate (FAC-LIP) was successfully prepared and intranasal administration of FAC-LIP increased both the total iron contents and iron storage protein (FTL) expression in rat olfactory bulb, cerebral cortex, striatum and hippocampus, compared with those of FAC groups. Moreover, there was not overtly toxic affects to brain, lung epithelial cells and tracheal mucosa.

Dataset Information

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

Background

Methods

Results

Publications

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

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