Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

Broide, Efrat; Reifen, Ram; Matalon, Shay; Berkovich, Zipi; Shirin, Haim

doi:10.1155/2018/7494821

Cited by 6 publications

(10 citation statements)

References 10 publications

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“…In addition, as TFR and FPN1 is required for the transmembrane transport of iron (Broide et al., 2018), we therefore investigated their spinal expression in rats from four groups. The protein levels of TFR were increased and FPN1 was decreased in CCI‐treated rats in contrast to sham rats at POD‐5 (TFR: P CCI vs Sham = 0.003, FPN1: P CCI vs Sham = 0.003, Figure 2c,e) and POD‐10 (TFR: P CCI vs Sham = 0.003, FPN1: P CCI vs Sham = 0.001, Figure 2c,f,g).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of ferroptosis‐like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats

Guo

Xiao

et al. 2021

European Journal of Pain

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Background Relationships between iron‐dependent ferroptosis and nerve system diseases have been recently revealed. However, the role of ferroptosis in neuropathic pain (NeP) remains to be elucidated. Thus, we aimed to investigate whether ferroptosis in spinal cord contributes to NeP induced by a chronic constriction injury (CCI) of the sciatic nerve. Methods Forty Sprague‐Dawley rats received CCI or sham surgery, and were randomly assigned to the following four groups: sham group; CCI + LIP group; CCI + Veh group; and CCI group. Liproxstatin‐1 or corn oil were separately injected intraperitoneally for three consecutive days after surgery in the CCI + LIP or CCI + Veh group. The mechanical and thermal hypersensitivities were tested after surgery. Biochemical and morphological changes related to ferroptosis in the spinal cord were also assessed. These included iron content, glutathione peroxidase 4 (GPX4) and anti‐acyl‐CoA synthetase long‐chain family member 4 (ACSL4) expression, lipid peroxidation assays, as well as mitochondrial morphology. Results CCI‐induced NeP was followed by iron accumulation, increased lipid peroxidation and dysregulation of ACSL4 and GPX4. Moreover transmission electron microscopy confirmed the presence of aberrant morphological changes on mitochondrial, such as mitochondria shrinkage and membrane rupture. Furthermore, the administration of liproxstatin‐1 on CCI rats attenuated hypersensitivities, lowered the iron level, decreased spinal lipid peroxidation, restored the dysregulations in GPX4 and ACSL4 levels, and protected against CCI induced morphological changes in mitochondria. Conclusions Our findings indicated the involvement of ferroptosis in CCI induced NeP, and point to ferroptosis inhibitors such as liproxstatin‐1 as potential therapies for hypersensitivity induced by peripheral nerve injury. Significance The spinal ferroptosis‐like cell death was involved in the development of neuropathic pain resulted from peripheral nerve injury, and inhibition of ferroptosis by liproxstatin‐1 could alleviate mechanical and thermal hypersensitivities. This knowledge suggested that ferroptosis could represent a potential therapeutic target for neuropathic pain.

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Section: Resultsmentioning

confidence: 99%

Inhibition of ferroptosis‐like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats

Guo

Xiao

et al. 2021

European Journal of Pain

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“…Worldwide, the development and introduction of new iron-containing compounds for the timely carrying out of preventive measures is one of the main tasks in the fight against anemia (Meier et al, 2011;Jiefen et al, 2017;Kim et al, 2018). Also this illness is diagnosed by iron deficiency in combination with other pathologies, for example diabetes (Walter et al, 1998;Shirinova, 2005;Broide et al, 2018). Therefore, the relevance of the study of new complexes of the iron of various valences, which are synthesized in the field of chemistry, is not lost.…”

Section: Discussionmentioning

confidence: 99%

“…At present, knowledge about the value of iron for metabolic processes (Bonkovsky & Herbert, 1991;Ganz, 2013;Dos Santos Vieira et al, 2018) and its use in combination with other substances, such as vitamins (Diel et al, 2018;Pillay et al, 2018), microelements (Todoriuk et al, 2018;Terpilowska & Siwicki, 2018, 2019 or in the form of nanocrystals (Zheng et al, 2008) for different routes of the administration (Maes et al, 2011;Peña-Rosas et al, 2015;Stephanyk et al, 2017) is deepened. This is relevant in connection with the worldwide registration of iron deficiency anemia (Batrakov, 2005;Killip & Bennett, 2008;Dela Cruz-Góngora, 2018), sometimes in combination with diabetes (Broide, 2018;Miranda, 2018) or other diseases (Yeh et al, 2019). Analyzing the literature data on corresponding topics, we also noticed that within an in-depth study of the properties of the bivalent iron (ІІ) and the trivalent iron (ІІІ) (Jiefen et al, 2017), the study of high-valent iron (ІV, V, VI) becomes very relevant.…”

Section: Introductionmentioning

confidence: 99%

Acute toxicity of the iron clathrochelate complexes

Dukhnytskyi

Derkach

Plutenko

et al. 2019

Regul. Mech. Biosyst.

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A new class of highly valent iron compounds is formed by atmospheric oxidation in aqueous media and it is extremely stable both in solid and soluble conditions and may exist indefinitely in a medium without signs of degradation. The first clathrochelate complexes of iron (IV) are infinitely stable in water and readily available from simple, commercially available, inexpensive source materials with surprisingly mild reaction conditions. To create new drugs on their bases, research on their toxicity is required. In this study, the results of preclinical studies of a new iron clathrochelates drug are presented. Experiments were carried out on white rats and quails, which in the previous experiment were divided into five experimental and two control groups. The solution of iron clathrochelate complexes was administered intragastrically in doses 50, 500, 1000, 2000 and 5000 mg/kg, respectively. Our results have shown that there were no grounds for using rats in the advanced experiment because the conducted research has established that iron clathrochelate is non toxic to rats. Thus, the minimum dose of iron clathrochelate complexes did not cause death of quails, and the largest dose caused 100% mortality. The basic experiment was conducted on 6 groups of birds, each consisting of 7 quails. The drug was administered in the following doses: 500, 600, 700, 800, 900, 1000 mg/kg. The monitoring observation of the laboratory birds lasted for 14 days. It has been established that the average lethal dose of clathrochelate of the investigated drug for internal administration in quails is 764 ± 33 mg/kg. According to the classification of chemicals by the degree of danger (State ST 12.1.007-76), iron (IV) clathrochelate complexes correspond to the third class of hazard, and according to the classification of substances for toxicity they are classified as category 4 (low toxicity substances). The prospect of further research is to investigate the pharmacological and toxicological properties of iron (IV) clathrochelate for chronic toxicity.

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“…It is worth noting that anemia is correlated with obesity in young patients; low-grade inflammation was observed to be a risk factor for ID even in schoolchildren [45]. Type 1 and 2 diabetes are widespread pathologies that appear to be associated with ID; the coexistence of high glucose levels and inflammatory cytokines impairs or reduces intestinal iron absorption through enterocyte iron transporters downregulation [46,47].…”

Section: Introductionmentioning

confidence: 99%

Iron-Enriched Nutritional Supplements for the 2030 Pharmacy Shelves

et al. 2021

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Iron deficiency (ID) affects people of all ages in many countries. Due to intestinal blood loss and reduced iron absorption, ID is a threat to IBD patients, women, and children the most. Current therapies can efficiently recover normal serum transferrin saturation and hemoglobin concentration but may cause several side effects, including intestinal inflammation. ID patients may benefit from innovative nutritional supplements that may satisfy iron needs without side effects. There is a growing interest in new iron-rich superfoods, like algae and mushrooms, which combine antioxidant and anti-inflammatory properties with iron richness.

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Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

Cited by 6 publications

References 10 publications

Inhibition of ferroptosis‐like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats

Inhibition of ferroptosis‐like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats

Acute toxicity of the iron clathrochelate complexes

Iron-Enriched Nutritional Supplements for the 2030 Pharmacy Shelves

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