BACKGROUND: Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity. METHODS: Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups. RESULTS: CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration. CONCLUSION: ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.
BACKGROUND:Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsAnephrotoxicity. METHODS:Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups. RESULTS:CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration. CONCLUSION:ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsAnephrotoxicity model.
Authors: Carla P Carlos; Glória E F Mendes; André R Miquelin; Marcus A M Luz; Cleonice G A da Silva; Nico van Rooijen; Terezila M Coimbra; Emmanuel A Burdmann Journal: Transplantation Date: 2010-06-15 Impact factor: 4.939
Authors: Leandro P Araujo; Renata R Truzzi; Gloria E Mendes; Marcus A M Luz; Emmanuel A Burdmann; Sonia M Oliani Journal: Am J Nephrol Date: 2010-05-18 Impact factor: 3.754
Authors: Fernando N Facio; Angela A Sena; Leandro P Araújo; Gloria E Mendes; Isac Castro; Marcus A M Luz; Luis Yu; Sonia Maria Oliani; Emmanuel A Burdmann Journal: J Mol Med (Berl) Date: 2010-10-16 Impact factor: 4.599
Authors: Alvaro Yogi; Glaucia E Callera; Sarah O'Connor; Tayze T Antunes; William Valinsky; Perrine Miquel; Augusto C I Montezano; Anne-Laure Perraud; Carsten Schmitz; Alvin Shrier; Rhian M Touyz Journal: Cell Signal Date: 2013-07-06 Impact factor: 4.315