In Vitro and In Vivo Evaluations of Mesoporous Iron Particles for Iron Bioavailability

Lin, Jung-Feng; Wu, Chau-Chung; Liao, Yu-Jiun; Jakfar, Subhaini; Tang, Zi-Biao; Chen, Jhewn‐Kuang; Lin, Feng‐Huei

doi:10.3390/ijms20215291

Cited by 11 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Incubation with ferric iron has been reported to increase ferritin expression in Caco-2 cells [54] and astrocytes [55] as a potential cellular defense mechanism against iron overload which is in line with our results (Fig. 2e).…”

Section: Discussionsupporting

confidence: 92%

Dithiolethiones Protect Against Iron Overload-Induced Cytotoxicity and Serve as Ferroptosis Inhibitors in U-87 MG Cells

Kulkarni

Gadde

Betharia

2022

Preprint

View full text Add to dashboard Cite

Iron overload-induced oxidative stress is known to trigger various cell death pathways such as apoptosis, necrosis, autophagy, and a novel iron-dependent, non-apoptotic form of cell death known as ferroptosis. Ferroptosis is driven by excessive lipid peroxidation coupled with reduced cellular antioxidant capacity and is implicated in iron overload-related neurodegenerative disorders. Dithiolethiones have emerged as promising compounds owing to their lipophilicity and cytoprotective potential against a wide range of toxicants. The two dithiolethiones 3H-1,2-dithiole-3-thione (D3T) and 5-amino-3-thioxo-3H-(1,2) dithiole-4-carboxylic acid ethyl ester (ACDT) have previously been reported to display neuroprotection by a Nrf2-mediated upregulation of the endogenous antioxidant machinery. Here, we test them against ferric ammonium citrate (FAC)-induced toxicity in U-87 MG astrocytoma cells. Exposure to 15 mM FAC for 24 hours resulted in 53% cell death. A 24-hour pretreatment with 50 µM D3T and ACDT reversed this cytotoxicity with D3T being more efficacious compared to the standard antioxidant N-acetylcysteine (NAC). Both dithiolethiones exhibited antioxidant effects by counteracting FAC-induced ROS and lipid peroxidation, reducing the need for GSH induction, and upregulating ferritin expression. Ferrostatin-1 (10 µM), a ferroptosis-specific inhibitor, inhibited FAC-induced ROS production, lipid peroxidation, and cell death, indicating for the first time that FAC induces ferroptosis in U-87 MG cells. A 24 hour pretreatment with dithiolethiones reversed erastin-induced ferroptosis by upregulating the xCT transporter and intracellular GSH levels thereby alleviating lipid peroxidation. RSL3-induced ferroptotic cell death and lipid peroxidation were also counteracted by pretreatment with D3T and ACDT. Collectively, our findings demonstrate that dithiolethiones are promising therapeutic compounds for the treatment of iron overload disorders involving ferroptotic cell death.

show abstract

Section: Discussionsupporting

confidence: 92%

Dithiolethiones Protect Against Iron Overload-Induced Cytotoxicity and Serve as Ferroptosis Inhibitors in U-87 MG Cells

Kulkarni

Gadde

Betharia

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…However, only 38HT had higher RBV than EIP. It is important to note that the RBV of all the iron powders was >80% and is in contrast with previous reported RBV of EIP, which is 40%−60% (Lin et al, 2019;Lynch et al, 2007;Maekawa et al, 2006;Pennell, et al, 1975;Swain et al, 2003). This could be due to the differences in diet composition; in the present study, egg albumin was used as a source of protein while others used casein, which is a known inhibitor of iron absorption (Hurrell et al, 1989).…”

Section: Discussioncontrasting

confidence: 82%

“…During iron deficiency anemia, most of the iron is shuttled for the regeneration of Hb. Therefore, Hb regeneration in iron‐depleted rat models is used to assess the relative bioavailability or relative biological value (RBV) of iron from different sources (Lin et al., 2019; Maekawa et al., 2006; Swain et al., 2003). Dietary depletion of iron led to a significant reduction in Hb and plasma ferritin levels, implying the development of iron deficiency anemia.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Bioavailability of iron from novel hydrogen reduced iron powders: Studies in Caco‐2 cells and rat model

Jyrwa

Yaduvanshi

Sinha

et al. 2021

Journal of Food Science

View full text Add to dashboard Cite

The bioavailability of iron from elemental iron powders, including hydrogen reduced iron powder (HRIP), is influenced by particle size and surface area. In the present study, we investigated the solubility, bioaccessibility, and bioavailability of iron from novel HRIPs (particle size ≤25 and 38 µm generated at low [LT] and high [HT] temperature), with porous morphology and high surface area, in intestinal Caco-2 cells and in rat models. The acceptability of fortified wheat flour was tested in human volunteers. The iron solubility and ferritin induction in Caco-2 cells were significantly higher from wheat flour fortified with HRIPs compared to electrolytic iron powder (EIP, ≤45 µm size) either in the absence or presence of ascorbic acid. Nevertheless, ferritin induction in Caco-2 cells was significantly higher with FeSO 4 compared to HRIP or EIP. The relative biological value of HRIPs was significantly higher (≤38HT) or similar compared to EIP in rats. However, serum ferritin was significantly higher in rats fed HRIPs than EIP. Further, wheat flour fortified with HRIP was found to be acceptable for consumption. These findings demonstrate higher iron bioavailability from novel HRIPs compared to the reference EIP (≤45 µm) and merits further studies on toxicity and efficacy.Practical Application: The use of elemental iron powders for food fortification to alleviate iron deficiency is limited due to its poor bioavailability. The novel hydrogen-reduced elemental iron powders used in this study had higher bioaccessibility and bioavailability compared to reference EIP (≤45 µm) in in vitro and in vivo models, respectively. Further, there were no sensory differences between roti prepared with fortified or unfortified wheat flour. These results suggest that the novel hydrogen reduced elemental iron powders used in the present study are suitable for wheat flour fortification.

show abstract

“…Iron sulfate is the pioneer of NPs and is followed by newer particles [48]. Negatively charged or liposoluble particles cross the membrane more easily while mesoporous iron has higher bioavailability compared with iron salts due to the smaller size and larger surface area after dissolution at gastric pH [49,50].…”

Section: Nanoparticles To Improve Bioavailability Iron Administrationmentioning

confidence: 99%

Iron, Copper, and Zinc Homeostasis: Physiology, Physiopathology, and Nanomediated Applications

2021

View full text Add to dashboard Cite

Understanding of how the human organism functions has preoccupied researchers in medicine for a very long time. While most of the mechanisms are well understood and detailed thoroughly, medicine has yet much to discover. Iron (Fe), Copper (Cu), and Zinc (Zn) are elements on which organisms, ranging from simple bacteria all the way to complex ones such as mammals, rely on these divalent ions. Compounded by the continuously evolving biotechnologies, these ions are still relevant today. This review article aims at recapping the mechanisms involved in Fe, Cu, and Zn homeostasis. By applying the knowledge and expanding on future research areas, this article aims to shine new light of existing illness. Thanks to the expanding field of nanotechnology, genetic disorders such as hemochromatosis and thalassemia can be managed today. Nanoparticles (NPs) improve delivery of ions and confer targeting capabilities, with the potential for use in treatment and diagnosis. Iron deficiency, cancer, and sepsis are persisting major issues. While targeted delivery using Fe NPs can be used as food fortifiers, chemotherapeutic agents against cancer cells and microbes have been developed using both Fe and Cu NPs. A fast and accurate means of diagnosis is a major impacting factor on outcome of patients, especially when critically ill. Good quality imaging and bed side diagnostic tools are possible using NPs, which may positively impact outcome.

show abstract

In Vitro and In Vivo Evaluations of Mesoporous Iron Particles for Iron Bioavailability

Cited by 11 publications

References 24 publications

Dithiolethiones Protect Against Iron Overload-Induced Cytotoxicity and Serve as Ferroptosis Inhibitors in U-87 MG Cells

Dithiolethiones Protect Against Iron Overload-Induced Cytotoxicity and Serve as Ferroptosis Inhibitors in U-87 MG Cells

Bioavailability of iron from novel hydrogen reduced iron powders: Studies in Caco‐2 cells and rat model

Iron, Copper, and Zinc Homeostasis: Physiology, Physiopathology, and Nanomediated Applications

Contact Info

Product

Resources

About