Furosemide Reduces TNF Levels and Increases Antioxidant Activity in Animal Models of Nephrotic Syndrome

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.