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- Potential anti-inflammatory effect of erythropoietin in non-clinical studies in vivo: a systematic reviewPublication . Silva, Inês; Alípio, Carolina; Pinto, Rui; Mateus, VanessaErythropoietin (EPO) is a hypoxia-induced hormone produced in adult kidneys with erythropoietic and non-erythropoietic effects. In vivo studies represent an important role to comprehend the efficacy and safety in the early phase of repurposing drugs. The aim is to evaluate the potential anti-inflammatory effect of EPO observed in animal models of disease. Following PRISMA statements, electronic database Medline via PubMed platform was used to search articles with the research expression ((erythropoietin [MeSH Terms]) AND (inflammation [MeSH Terms]) AND (disease models, animal [MeSH Terms])). The inclusion criteria were original articles, studies where EPO was administered, studies where inflammation was studied and/or evaluated, non-clinical studies in vivo with rodents, and articles published in English. Thirty-six articles met the criteria for qualitative analysis. Exogenous EPO was used in models of sepsis, traumatic brain injury, and autoimmune neuritis, with an average of 3000 IU/Kg for single and multiple doses, using mice and rats. Biomarkers such as immune-related effectors, cytokines, reactive oxygen species, prostaglandins, and other biomarkers were assessed. EPO has been recognized as a multifunctional cytokine with anti-inflammatory properties, showing its significant effect both in acute and chronic models of inflammation. Further non-clinical studies are suggested for the enlightenment of anti-inflammatory mechanisms of EPO in lower doses, allowing us to understand the translational data for humans.
- Erythropoietin in animal models of inflammationPublication . Silva, Inês; Alípio, Carolina; Pinto, Rui; Mateus, VanessaBackground: Erythropoietin binds to the erythropoietin receptor to promote the proliferation and differentiation of red blood cells. This hypoxia-induced hormone is produced in adult kidneys with erythropoietin and non-erythropoietic effects. Since current anti-inflammatory therapies are not safe, erythropoietin emerges as a new pharmacological approach reverting the mechanism of inflammation with apparently lower toxicity. AIM: Evaluate the potential anti-inflammatory effect of erythropoietin observed in animal inflammatory disease models. Methods: A systematic review followed PRISMA statements in the electronic database MEDLINE via the PubMed platform. The inclusion criteria were: (1) original articles; (2) studies in animal models where erythropoietin was administered; (3) studies where inflammation was studied and/or evaluated; (4) non-clinical studies in vivo with rodents; and (5) articles published in English. Results: A total of 36 articles met the criteria for qualitative analysis. Exogenous erythropoietin was used in models of sepsis, traumatic brain injury, and autoimmune neuritis with anti-inflammatory effects. The average dose of exogenous erythropoietin was 3000 IU/kg of weight. Erythropoietin was associated with a significant reduction of biomarkers such as immune-related effectors, cytokines, reactive oxygen species, and prostaglandins. Erythropoietin analogues, such as ARA290 or carbamylated erythropoietin, have the crucial advantage of promoting the anti-inflammatory effect without the thromboembolic risk by the proliferation of red blood cells. Conclusion: Erythropoietin is recognized as a multifunctional cytokine with anti-inflammatory properties, showing its significant effect both in acute and chronic murine models of inflammation.