Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways

Ghassemi-Barghi, Nasrin; Ehsanfar, Zeynab; Mohammadrezakhani, Omid; Ashari, Sorour; Ghiabi, Shamim; Bayrami, Zahra

doi:10.1007/s10753-022-01737-7

Cited by 4 publications

(3 citation statements)

References 68 publications

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“…21 As anticipated, this study revealed no significant changes in peripheral blood erythropoietic parameters, serum AST, ALT, LDH, and spleen weight and length after ARA290 treatment. As mentioned earlier, the anti-apoptotic and anti-inflammatory activities of ARA290 have been confirmed by previous studies in various models, 22,23 and our results further demonstrated that these ARA290 effects extend to cerebral ischemic models. Untargeted LC-MS/MS analyses revealed that the primary differential metabolites affected by ARA290 were associated with the pathophysiology of the vascular endothelium, which may be related to its anti-apoptotic and anti-inflammatory properties.…”

Section: Temporal Changes In β Cr Protein Levels Are Related To Degre...supporting

confidence: 91%

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

Wang,

Yang,

Huang

et al. 2024

CNS Neurosci Ther

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AimTo explore the neuroprotective effects of ARA290 and the role of β‐common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO).MethodsThis study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO‐induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5‐triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry‐based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot.ResultsARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR.ConclusionARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

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Section: Temporal Changes In β Cr Protein Levels Are Related To Degre...supporting

confidence: 91%

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

Wang,

Yang,

Huang

et al. 2024

CNS Neurosci Ther

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“…To avoid this problem, we use ARA 290, which is an 11-amino acid peptide developed from the three-dimensional structure of helix B of the EPO molecule that interacts with the IRR. Therefore the present study evaluated the in-vivo e cacy of ARA290 in stimulating wound healing in diabetics animals [9].…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulation of glucose homeostasis and raised glucose levels are the crucial etiologies of diabetes [6]. Hyperglycemia enhances the levels of proin ammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, IL-10, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces oxidative stress, and these factors primarily cause impaired wound healing [7][8][9]. Extreme origination of reactive oxygen species (ROS), lead to damages to cellular membranes, lipids, proteins, and DNA, becomes adverse to wound healing [10,11].…”

Section: Introductionmentioning

confidence: 99%

An in vivo investigation on the wound-healing activity of Specific ligand for the innate repair receptor, ARA290, using a diabetic animal model

Mashreghi¹,

Bayrami

Sichani

et al. 2023

Preprint

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The diabetic foot ulcer (DFU) are serious problems to diabetes and may be associated with late healing and septic manifestation, consequently result in amputation which is an extortionate incident. The innate repair receptor (IRR) is expressed by injured tissues and is activated by erythropoietin produced and released into damaged tissue. Activation of the IRR might provide benefit for diabetic wound healing. This study evaluated effect of a specific IRR agonist, ARA290, on skin wound repair. The aim of the present study was to evaluate the effect of topical application based on ARA290, in streptozotocin-induced diabetic incision wound models rats. The treatment was performed daily, until day 14 after wound induction. Wound closure was determined and the features of the repaired tissue were examined, including amount of collagen and protein content, biochemical parameters, antioxidant status and proinflammatory cytokines. The data confirmed wound healing activities via macroscopic, biochemical, immunofluorescent and molecular methods. There was meaningful acceleration in wound closure rate, decrease in the period of re-epitalization, greater amount of collagen and protein content in ARA290 treated group when compared with control group. The increase of serum insulin and HDL was divergent with blood glucose decrease and reduced lipid level. The healing effect was confirmed by reduced levels of inflammatory cytokines and lipid peroxidation and augmented antioxidants. The results propose that ARA290-arbitrated IRR activation may signify an appealing approach to treat diabetes-associated wound healing.

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Erythropoietin enhances iron bioavailability in HepG2 cells by downregulating hepcidin through mTOR, C/EBPα and HIF-1α

Maltaneri,

Chamorro,

Gionco

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways

Cited by 4 publications

References 68 publications

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

An in vivo investigation on the wound-healing activity of Specific ligand for the innate repair receptor, ARA290, using a diabetic animal model

Erythropoietin enhances iron bioavailability in HepG2 cells by downregulating hepcidin through mTOR, C/EBPα and HIF-1α

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