Furosemide Reduces TNF Levels and Increases Antioxidant Activity in Animal Models of Nephrotic Syndrome
Bianca Lara Silva Amaral
Programa de Pós-Graduação em Ciências Farmacêuticas – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Tatiele Pereira dos Santos
Programa de Pós-Graduação em Ciências Farmacêuticas – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Rafaela Mendes dos Santos
Programa de Pós-Graduação em Ciências da Saúde – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Pedro Figueiredo Pereira de Andrade
Programa de Pós-Graduação em Odontologia – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Arthur Rocha-Gomes
Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas – SBFisio/ UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Vinícius Jaskolka Lages
Programa de Pós-Graduação em Ciências Farmacêuticas – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Karine Beatriz Costa
Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas – SBFisio/ UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Daniel Almeida Freitas
Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas – SBFisio/ UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Bruno Ferreira Mendes
Programa de Pós-Graduação em Ciências da Saúde – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Gustavo Eustáquio Brito Alvim de Melo
Programa de Pós-Graduação em Ciências Farmacêuticas – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil and Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas – SBFisio/ UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
Wagner de Fátima Pereira
*
Programa de Pós-Graduação em Ciências Farmacêuticas – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil, Programa de Pós-Graduação em Ciências da Saúde – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil and Programa de Pós-Graduação em Odontologia – UFVJM, Laboratory of Immunology (LABIMUNO) and Biological Testing Laboratory (LEB) / Integrated Postgraduate and Research Center (CIPq) - Federal University of Jequitinhonha and Mucury Valleys (UFVJM) - 5000 Alto da Jacuba, MGT 367 highway, Diamantina, Brazil.
*Author to whom correspondence should be addressed.
Abstract
Nephrotic syndrome (NS) is a renal condition characterized by proteinuria, edema formation, hypoalbuminemia and dyslipidemia. Evidence indicates that the immune response plays a fundamental role in disease evolution and maintenance. Although diuretics are used in the NS treatment, it is not known whether they have any effect on immune and redox responses. Therefore, the aim of the present study was to evaluate the furosemide effects in the inflammatory and redox responses in a doxorubicin- induced NS model. Eighteen male adult Wistar rats were divided into 3 groups: Control (n = 6) - received intravenous injection of saline solution; DOXO (n = 6) - received intravenous injection of doxorubicin (7.5 mg/kg); DOXO-F (n = 6) - received intravenous injection of doxorubicin (7.5 mg/kg) and were later treated with furosemide by gavage (5.0 mg/kg). At the end of 36 days of treatment were evaluated: urine protein concentration, blood leukocyte count, kidney histology, cytokine levels (TNF-α, INF-γ and TGF-β), antioxidant levels (FRAP) and enzyme activity (CAT and SOD), besides markers of oxidative stress (TBARS and protein carbonyl) in renal tissue. Data were analyzed with ANOVA and Tukey test when necessary (p < 0.05). Furosemide, at the dosage used in this study, promoted increased in global blood leukocytes and reduced lymphocyte blood count. It was also observed that furosemide reduced TNF-α and increased TGF-β levels in renal tissue. In addition, furosemide increased the levels of oxidative stress markers (TBARS and protein carbonyls) and the activity of antioxidant enzymes (SOD and CAT). Thus, furosemide showed anti-inflammatory effects in rats with nephropathy, by reducing TNFα levels and increasing antioxidant activity in kidney tissue.
Keywords: Nephrotic syndrome, furosemide, animal model, cytokines, redox status