Effects of previous physical training on adriamycin nephropathy and its relationship with endothelial lesions and angiogenesis in the renal cortex

Aims: Adriamycin (ADR)-induced nephropathy is one of the most experimental models used in progressive kidney disease. A single dose of this drug induces a progressive and irreversible proteinuria that progresses to focal segmental glomerulosclerosis and tubulointerstitial lesions. Regular physical activity has been considered as a therapeutic intervention in several diseases. This study evaluated the influence of previous physical training in renal damage induced by ADR and the role of endothelial lesions and angiogenesis in this process. Main methods: Male Wistar rats were subjected or not to treadmill running for 4 weeks and then injected with ADR (25 mg/kg, i.v.) or saline. Twenty-four-hour urine samples were collected for albuminuria measurement, and blood samples were collected to measure plasma creatinine 60 days after the injections. The kidneys were removed for histological, immunohistochemical, Western blot and ELISA studies. Key findings: ADR-treated rats presented increases in plasma creatinine levels, albuminuria, podocyte damage, and enlargement of the tubular interstitial relative area, as well as higher macrophage numbers in the renal cortex, interleukin (IL)-1 beta levels in renal tissue and urinary monocyte chemoattractant protein (MCP)-1, which were associated with reduction in vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) expressions and peritubular capillary (FTC) density in renal cortex. These alterations were less intense in the animals subjected to previous exercise training. Significance: Physical training prior to ADR injection reduced the renal damage induced by this drug. This effect was related to angiogenesis and reduction in the endothelial lesions and inflammatory process in the renal cortex of these animals. (C) 2016 Elsevier Inc. All rights reserved. (AU)