Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats.

BACKGROUND/AIMS: Physical training has beneficial effects on endothelial function and can influence the regeneration of the endothelial cell. We investigated the effect of physical training on cisplatin (CP)-induced acute kidney injury and assessed the impact of training on endothelial structure and function, and on the inflammatory processes in rats. METHODS: We injected male Wistar rats subjected to previous physical training in treadmill running (trained, TR) or not (sedentary, SED) with CP (5 mg/kg) (TR+CP and SED+CP groups, respectively). Five days after the injections, blood and urine samples were collected to evaluate renal function and kidneys were harvested for morphological, immunohistochemical, enzyme-linked immunosorbent assay, and analysis of nitric oxide (NO) levels. RESULTS: Rats treated with CP showed increased levels of plasma creatinine and sodium and potassium fractional excretion. These alterations were associated with increase in tubulointerstitial lesions and macrophage number, reduction of endothelial cells, and increased VEGF, vimentin, and α-smooth muscle actin expression in the outer renal medulla in the SED+CP group. We also found increased levels of renal IL-1ß and increased excretion of monocyte chemoattractant protein-1 and transforming growth factor-ß compared with controls. These changes were milder in trained rats, associated with increased levels of renal tissue NO, and increased expression of p-eNOS and stromal cell-derived factor-1α (a chemokine involved in kidney repair) in the kidneys of CP-injected trained rats. CONCLUSIONS: The protective effect of previous training in CP-treated rats was associated with reduced endothelial cell lesions and increased renal production of NO in trained rats.

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 4weeks and then injected with ADR (2.5mg/kg, i.v.) or saline. Twenty-four-hour urine samples were collected for albuminuria measurement, and blood samples were collected to measure plasma creatinine 60days 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)-1ß 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 (PTC) 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.