AIM: Proteinuria is not only a common marker of renal disease, but also involved in renal tubulointerstitial inflammation and fibrosis. The aim of this study was to investigate the mechanisms underlying the protective effects of enalapril, an ACEI, against nephropathy in rats. METHODS: Wistar rats underwent unilateral right nephrectomy, and then were treated with BSA (5 g·kg(-1)·d(-1), ip), or BSA plus enalapril (0.5 g·kg(-1)·d(-1), po) for 9 weeks. The renal lesions were evaluated using histology and immunohistochemistry. The expression of NLRP3, caspase-1, IL-1β and IL-18 was analyzed using immunohistochemistry, RT-PCR and Western blot. RESULTS: BSA-overload resulted in severe proteinuria, which peaked at week 7, and interstitial inflammation with prominent infiltration of CD68(+) cells (macrophages) and CD3(+) cells (T lymphocytes), particularly of CD20(+) cells (B lymphocytes). BSA-overload markedly increased the expression of NLRP3, caspase-1, IL-1β and IL-18 in the proximal tubular epithelial cells, and in inflammatory cells as well. Furthermore, the expression of IL-1β or IL-18 was significantly correlated with proteinuria (IL-1β: r=0.757; IL-18: r=0.834). These abnormalities in BSA-overload rats were significantly attenuated by concurrent administration of enalapril. CONCLUSION: Enalapril exerts protective effects against BSA-overload nephropathy in rats via suppressing NLRP3 inflammasome expression and tubulointerstitial inflammation.
AIM: Proteinuria is not only a common marker of renal disease, but also involved in renal tubulointerstitial inflammation and fibrosis. The aim of this study was to investigate the mechanisms underlying the protective effects of enalapril, an ACEI, against nephropathy in rats. METHODS:Wistar rats underwent unilateral right nephrectomy, and then were treated with BSA (5 g·kg(-1)·d(-1), ip), or BSA plus enalapril (0.5 g·kg(-1)·d(-1), po) for 9 weeks. The renal lesions were evaluated using histology and immunohistochemistry. The expression of NLRP3, caspase-1, IL-1β and IL-18 was analyzed using immunohistochemistry, RT-PCR and Western blot. RESULTS: BSA-overload resulted in severe proteinuria, which peaked at week 7, and interstitial inflammation with prominent infiltration of CD68(+) cells (macrophages) and CD3(+) cells (T lymphocytes), particularly of CD20(+) cells (B lymphocytes). BSA-overload markedly increased the expression of NLRP3, caspase-1, IL-1β and IL-18 in the proximal tubular epithelial cells, and in inflammatory cells as well. Furthermore, the expression of IL-1β or IL-18 was significantly correlated with proteinuria (IL-1β: r=0.757; IL-18: r=0.834). These abnormalities in BSA-overload rats were significantly attenuated by concurrent administration of enalapril. CONCLUSION:Enalapril exerts protective effects against BSA-overload nephropathy in rats via suppressing NLRP3 inflammasome expression and tubulointerstitial inflammation.
Authors: Alberto Radaelli; Claudia Loardi; Maria Cazzaniga; Giulia Balestri; Caterina DeCarlini; M Grazia Cerrito; Elena Negro Cusa; Luca Guerra; Stefano Garducci; Danilo Santo; Lorenzo Menicanti; Giovanni Paolini; Arianna Azzellino; Maria Luisa Lavitrano; Giuseppe Mancia; Alberto U Ferrari Journal: Arterioscler Thromb Vasc Biol Date: 2007-09-06 Impact factor: 8.311
Authors: Min Xu; Dan Liu; Li-hong Ding; Kun-ling Ma; Min Wu; Lin-li Lv; Yi Wen; Hong Liu; Ri-ning Tang; Bi-cheng Liu Journal: Acta Pharmacol Sin Date: 2014-11-17 Impact factor: 6.150
Authors: Gabriel R Estrela; Frederick Wasinski; Marcos F Gregnani; Leandro C Freitas-Lima; Adriano C Arruda; Rafael Leite Morais; Denise Mac Malheiros; Niels O S Camara; João Bosco Pesquero; Michael Bader; Carlos Castilho Barros; Ronaldo Carvalho Araújo Journal: Front Mol Biosci Date: 2020-05-20