RESUMEN
Acute kidney injury (AKI) is characterized by rapid and potentially reversible decline in renal function; however, the current management for AKI is nonspecific and associated with limited supportive care. Considering the need for more novel therapeutic approaches, we believe that lectins from Dioclea violacea (Dvl), based on their anti-inflammatory properties, could be beneficial for the treatment of AKI induced by renal ischemia/reperfusion (IR). Dvl (1 mg/kg, i.v.) or vehicle (100 µL) was administered to Wistar rats prior to the induction of bilateral renal ischemia (45 min). Following 24 hours of reperfusion, inulin and para-aminohippurate (PAH) clearances were performed to determine glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF) and renal vascular resistance (RVR). Renal inflammation was assessed using myeloperoxidase (MPO) activity. Kidney sections were stained with hematoxylin-eosin to evaluate morphological changes. Intracellular superoxide anions, hydrogen peroxide, peroxynitrite, nitric oxide and apoptosis were analyzed using flow cytometry. IR resulted in diminished GFR, RPF, RBF, and increased RVR; however, these changes were ameliorated in rats receiving Dvl. AKI-induced histomorphological changes, such as tubular dilation, tubular necrosis and proteinaceous casts, were attenuated by Dvl administration. Treatment with Dvl resulted in diminished renal MPO activity, oxidative stress and apoptosis in rats submitted to IR. Our data reveal that Dvl has a protective effect in the kidney, improving renal function after IR injury, probably by reducing neutrophil recruitment and oxidative stress. These results indicate that Dvl can be considered a new therapeutic approach for AKI-induced kidney injury.
RESUMEN
BACKGROUND/AIMS: The rat has been the most used experimental animal for studies of cardiovascular and kidney diseases. However, it is notable that there is increasing importance placed on the use of the mouse model to increase understanding of these pathophysiologies. The aim of the present study was to induce chronic kidney disease in a mouse model and to evaluate the resulting changes in blood pressure (BP) and in renal morphology and function. METHODS: Adult male C57BL/6 mice underwent 5/6 nephrectomy (5/6 Nx) or a sham operation (Sham). Two weeks later, conscious animals were subjected to a 24-hour urine collection and to a direct measurement of BP. RESULTS: Compared to Sham animals, 5/6 Nx mice showed reduced creatinine clearance (3-fold, p<0.01), proteinuria (1.5-fold, p<0.01) and uremia (4-fold, p<0.01), as well as high blood pressure (~20%, p<0.01). 5/6 Nx animals showed increases in the 24 h urine excretion of Na(+) (2-fold, p<005), K(+) (~2-fold, <0.01) and Ca(2+) (~12-fold). Kidney histology of 5/6 Nx mice also demonstrated glomerular hypertrophy (1.5-fold, p<0.05), mesangial expansion (~40%, p<0.01) and increased glomerular collagen deposition (~30%, p<0.05). CONCLUSION: Induction of 5/6 nephrectomy in mice for two weeks leads to systemic arterial hypertension and to functional and morphological damage of the remnant kidney, which are considered the main characteristics of chronic kidney disease.
