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Pesquisa do Estado de Minas Gerais (FAPEMIG) / A s?ndrome nefr?tica (SN) ? definida por protein?ria maci?a, edema, hipoalb uminemia e hiperlipidemia e desenvolve a partir da les?o dos glom?rulos, especialmente d os pod?citos. Pode ser um a altera??o prim?ria (idiop?tica), com o uma doen?a espec?fica para os rins, ou secund?ria a alguma doen?a sist?mica pr?via. Histologicamente, a s?ndrome nefr?tica idiop?tica ( SNI ) ? definida pela combina??o das manifesta??es cl?nicas associadas ?s anormalidades histol?gicas inespec?ficas do rim, incluindo glomerulo esclerose focal e segmentar (GESF). A SN pode ser estudada, em modelo animal, por m eio de inje??es locais de Cloridrato de doxorrubicina ( Adriamicina? ) na dose de 7,5mg/kg em que, inje??o intravenosa ?nica pode induz ir protein?ria grave, semelhante ? observada em humanos. Embora os mecanismos patog?nicos da SNI persistam obscuros, altera ??es das respostas imunol?gicas , como as respostas at?picas dos linf?citos T e a atua??o de citocinas e quimiocinas, parecem estar envolvidas no dano aos glom?rulos. Neste sentido, a finalidade do presente estudo foi avaliar a participa??o de citocinas e q uimiocinas, por meio da express?o de IL - 1, IL - 4, CXCL1, CCL3/MIP - 1 e CCL5/RANTES em amostras de tecido renal e de urina, nos mecanismos de ativa??o e migra??o leucocit?ria, bem como as altera??es bioqu?micas, histol?gicas e biom?tricas em ratos com SN indu zida pela doxorrubicina. O protocolo experimental foi devidamente registrado e aprovado pela comiss?o de ?tica no uso de animais, da Universidade Federal dos Vales do Jequitinhonha e Mucuri (CEUA - UFVJM) sob o protocolo N? 029/2014. Foram utilizados 25 rato s machos ( Wistar ) , peso m?dio de 350 gramas e idade m?dia de seis semanas . Os animais foram divididos em dois grupos: CON (n=5), que recebeu inje??o endovenosa de solu??o salina como grupo controle e DOXO (n=25), que recebeu inje??o endovenosa de doxorrubi cina. Os animais do grupo DOXO foram eutanasiados e avaliados nos tempos 7, 14, 21 e 28 dias ap?s a inje??o. Foram coletadas amostras urin?rias (24 hs) e amostras sangu?neas ( pun??o card?aca). Ap?s a coleta sangu?nea, os ?rg?os foram perfundidos com solu?? o salina, sendo coletados os rins direito e esquerdo, que foram pesados e devidamente acondicionados , para posteriores an?lises biom?tricas, histol?gicas e imunol?gicas. A contagem total de leuc?citos foi realizada em c?mara de Neubauer. A avalia??o das am ostras urin?rias e teciduais para a detec??o de citocinas e quimiocinas foi realizada por ELISA. A nimais do grupo DOXO desenvolveram protein?ria a partir do 7 ? dia ap?s a inje??o de doxorrubicina , a qual permaneceu durante todo o per?odo experimental. O bse rvou - se, ainda, hipercreatininemia, altera??es biom?tricas , histol?gicas e dos leucogramas neste mesmo grupo . De modo geral, os animais expressaram maior concentra??o de citocinas e quimiocinas no tecido renal do que na s amostras de urina, sugestivo de um processo de secre??o relacionad o ? produ??o tecidual local. Al?m disso, o s resultados obtidos n o presente estudo proporciona ra m uma contribui??o in?dita em rela??o ? participa??o da quimiocina CXCL1 na fisiopatogenia da SN. Sua express?o n a urina pode r? es tar r elacionada com a instala??o das rea??es oxidativas nas fases iniciais da doen?a, conforme j? demonstrado por nosso grupo, nest e modelo experimental . Podendo, ainda, sugerir a participa??o de leuc?citos polimorfonucleares (neutr?filos) na etiopatogenia da SN , em sua fase inicial . Contudo, outros estudos ser?o necess?rios a fim de correlacionar a express?o tecidual d a citocina CXCL1 ? presen?a de neutr?filos no tecido renal e, consequente, produ??o de radicais livres neste modelo experimental de nefropat ia induzida pela doxorrubicina. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2018. / Nephrotic syndrome (NS) is defined by massive proteinuria, edema, hypoalbuminemia and hyperlipidemia and develops from th e lesion of the glomeruli, especially the podocytes. It can be a primary (idiopathic) change, as a specific disease for the kidneys, or secondary to some previous systemic disease. Histologically, idiopathic nephrotic syndrome (NIS) is defined by the combi nation of clinical manifestations associated with nonspecific histological abnormalities of the kidney, including f ocal and segmental glomerulosclerosis (GESF). SN may be studied in animal models by means of local injections of doxorubicin hydrochloride (Adriamycin?) at a dose of 7.5 mg/kg , in which single intravenous injection may induce severe proteinuria similar to that seen in humans. Although the pathogenic mechanisms of NIS persist obscure, changes in immune responses, such as atypical T lymphocyte re sponses and cytokine and chemokine activity, appear to be involved in damage to the glomeruli. In this sense, the purpose of the present study was to evaluate the participation of cytokines and chemokines through the expression of IL - 1, IL - 4, CXCL1, CCL3/M IP - 1 and CCL5/RANTES in renal and urine tissue samples in the activation and migration mechanisms as well as the biochemical, histological and biometric alterations in doxorubicin - induced SN rats. The experimental protocol was duly registered and approved by the Ethics Committee on Animal Use, Federal University of the Jequitinhonha and Mucuri Valleys (CEUA - UFVJM) under protocol No. 029/2014. Twenty - five male rats (Wistar), mean weight of 350 grams and mean age of six weeks, were used. The animals were divi ded into two groups: CON (n = 5), who received intravenous injection of saline as a control group and DOXO (n = 25), who received intravenous injection of doxorubicin. Animals from the DOXO group were euthanized and evaluated at times 7, 14, 21 and 28 days after injection. Urinary samples (24 h) and blood samples (cardiac puncture) were collected. After the blood collection, the organs were perfused with saline, and the right and left kidneys were collected, which were weighed and properly conditioned, for later biometric, histological and immunological analyzes. Total leukocyte count was performed in the Neubauer chamber. The evaluation of the urinary and tissue samples for the detection of cytokines and chemokines was performed by ELISA. Animals from the D OXO group developed proteinuria from the 7th day after the injection of doxorubicin, which remained throughout the experimental period. Hypercreatininemia, biometric, histological and leukogram changes were also observed in this same group. In general, the animals expressed a higher concentration of cytokines and chemokines in the renal tissue than in the urine samples, suggestive of a secretory process related to the local tissue production. In addition, the results obtained in the present study provided a n unprecedented contribution to the participation of chemokine CXCL1 in the pathophysiology of NS. Its expression in urine may be related to the establishment of oxidative reactions in the early stages of the disease, as demonstrated by our group in this e xperimental model . It may suggest the participation of polymorphonuclear leukocytes (neutrophils) in the etiopathogenesis of NS in its initial phase. However, other studies will be necessary in order to correlate the tissue expression of cytokine CXCL1 wit h the presence of neutrophils in the renal tissue and, consequently, the production of free radicals in this experimental model of nephropathy induced by doxorubicin.