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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.
- Effect of carbamylated erythropoietin in a chronic model of TNBS-induced colitisPublication . Silva, Inês; Gomes, Mário; Alípio, Carolina; Vitoriano, Jéssica; Estarreja, João; Mendes, Priscila; Pinto, Rui; Mateus, VanessaBackground: Inflammatory bowel disease (IBD) is a public health issue with a growing prevalence, which can be divided into two phenotypes, namely Crohn's disease (CD) and ulcerative colitis (UC). Currently, used therapy is based only on symptomatic and/or palliative pharmacological approaches. These treatments seek to induce and maintain remission of the disease and ameliorate its secondary effects; however, they do not modify or reverse the underlying pathogenic mechanism. Therefore, it is essential to investigate new potential treatments. Carbamylated erythropoietin (cEPO) results from the modification of the Erythropoietin (EPO) molecule, reducing cardiovascular-related side effects from the natural erythropoiesis stimulation. cEPO has been studied throughout several animal models, which demonstrated an anti-inflammatory effect by decreasing the production of several pro-inflammatory cytokines. Aim: This study aimed to evaluate the efficacy and safety of cEPO in a chronic TNBS-induced colitis model in rodents. Methods: Experimental colitis was induced by weekly intrarectal (IR) administrations of 1% TNBS for 5 weeks in female CD-1 mice. Then, the mice were treated with 500 IU/kg/day or 1000 IU/kg/day of cEPO through intraperitoneal injections for 14 days. Results: cEPO significantly reduced the concentration of alkaline phosphatase (ALP), fecal hemoglobin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Also, it demonstrated a beneficial influence on the extra-intestinal manifestations, with the absence of significant side effects of its use. Conclusion: Considering the positive results from cEPO in this experiment, it may arise as a new possible pharmacological approach for the future management of IBD.
- 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.