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      Cell therapy in renal ischemia/reperfusion experimental model using recombinant G-CSF

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      1 , , 1 , 2 , 2 , 2
      BMC Proceedings
      BioMed Central
      5th Congress of the Brazilian Biotechnology Society (SBBIOTEC)
      10-14 November 2013

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          Abstract

          Introduction The colony stimulating factor granulocyte (G-CSF) is a glycoprotein capable of promoting the survival, proliferation and differentiation of hematopoietic cells. Studies demonstrate the cytoprotective action of G-CSF against renal injury by ischemia/reperfusion injury in murine models. But the literature is still controversial in relation to the risk of worsening renal function after useG-CSF, which motivated the study to elucidate possible interference on the renal function of the treated animals. Objective Evaluate the renal function of rats after treatment with G-CSF at different doses of the drug. Methods Male Wistar rats (n = 18), 200g approx. (CEUA050/2013), divided into 3 groups (6 animals each) : control group (C) 5% glucose solution (solvent) groups treated with G-CSF at a dose of 10 (G10) and 50 (G50) mg / kg / per 5 days. After treatment, the rats were placed in metabolic cages for urine collection and obtaining urine volume. Values were obtained from creatinine, proteinuria, urea and number of circulating leukocytes. The results were expressed as mean ± SEM. The averages ofvalues between groups were calculated using one - way ANOVA followed by post hoc Fisher for comparison between differentgroups. Results A significant increase in the number of circulating leukocytes in animals treated with G- CSF (C = 9687 ± 899 / mm3;= 14375 ± 1967/mm3 G10, and G50 = 19670 ± 1663/mm3, p < 0.05). There was not a significant increase in urine volume after 24 hours treatment with G-CSF. There was no significant difference between the values of creatinine clearance, proteinuria and Urea, among groups C, G10 and G50. Conclusion There was no impairment of renal function in animals treated at doses of 10 and 50 mg / kg / per 5 days. Financial support: FAPES

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          Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution.

          Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability of hematopoietic stem cells, induced by stem cell factor and granulocyte colony-stimulating factor, to the injured kidney provides an adequate strategy for stem cell-based therapy to counteract renal ischemia/reperfusion injury. It is interesting that cytokine treatment before injury resulted in significant enhancement of function recovery of the kidney. This, however, was not due to increased incorporation of tubular epithelial cells from bone marrow origin. Importantly, cytokine treatment resulted in impaired influx of granulocytes into the injured kidney. Although cytokine treatment improved renal function rapidly after ischemic injury, the results show that the underlying mechanism likely is not based on stem cell transdifferentiation but rather on altered inflammatory kinetics.
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            Altered mitochondrial functioning induced by preoperative fasting may underlie protection against renal ischemia/reperfusion injury.

            We reported previously that the robust protection against renal ischemia/reperfusion (I/R) injury in mice by fasting was largely initiated before the induction of renal I/R. In addition, we found that preoperative fasting downregulated the gene expression levels of complexes I, IV, and V of the mitochondrial oxidative phosphorylation (OXPHOS) system, while it did not change those of complexes II and III. Hence, we now investigated the effect of 3 days of fasting on the functioning of renal mitochondria in order to better understand our previous findings. Fasting did not affect mitochondrial density. Surprisingly, fasting significantly increased the protein expression of complex II of the mitochondrial OXPHOS system by 19%. Complex II-driven state 3 respiratory activity was significantly reduced by fasting (46%), which could be partially attributed to the significant decrease in the enzyme activity of complex II (16%). Fasting significantly inhibited Ca(2+) -dependent mitochondrial permeability transition pore opening that is directly linked to protection against renal I/R injury. The inhibition of the mitochondrial permeability transition pore did not involve the expression of the voltage-dependent anion channel by fasting. In conclusion, 3 days of fasting clearly induces the inhibition of complex II-driven mitochondrial respiration state 3 in part by decreasing the amount of functional complex II, and inhibits mitochondrial permeability transition pore opening. This might be a relevant sequence of events that could contribute to the protection of the kidney against I/R injury. Copyright © 2012 Wiley Periodicals, Inc.
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              How Does G-CSF Act on the Kidney during Acute Tubular Injury?

              Recent findings in stem cell research have demonstrated multi-lineage plasticity of bone marrow cells, and also the contribution of hematopoietic bone marrow stem cells to the regeneration of injured organs including the kidney. These findings suggested the possibility of the use of granulocyte colony-stimulating factor (G-CSF) as a therapeutic option to regenerate injured organs. Recently, several studies regarding the effect of G-CSF on renal function have been reported in mouse models of acute renal failure. This series of experiments provided potentially important information regarding the treatment of patients with renal injury. This review summarizes the possible actions of G-CSF on the kidney, especially during acute tubular injury caused by toxic or ischemic insults.
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                Author and article information

                Conference
                BMC Proc
                BMC Proc
                BMC Proceedings
                BioMed Central
                1753-6561
                2014
                1 October 2014
                : 8
                : Suppl 4
                : P25
                Affiliations
                [1 ]PG Biotecnologia, UFES, Vitoria, Brasil
                [2 ]Departamento de Morfologia, UFES, Vitoria, Brasil
                Article
                1753-6561-8-S4-P25
                10.1186/1753-6561-8-S4-P25
                4204041
                8fc98748-7502-4220-9b37-fd535c60285a
                Copyright © 2014 Rodrigues et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                5th Congress of the Brazilian Biotechnology Society (SBBIOTEC)
                Florianópolis, Brazil
                10-14 November 2013
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                Medicine
                Medicine

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