Interaction of the anti-inflammatory annexin A1 protein and tacrolimus immunosuppressant in the renal function of rats

• Grant number: 10/06372-9
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: June 01, 2010
• End date: November 30, 2010
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Sonia Maria Oliani
• Grantee: Sonia Maria Oliani
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Background: Tacrolimus (FK) is currently widely used in transplant immunosuppression and autoimmune diseases treatment. However, FK induces nephrotoxicity, which is characterized by renal functional and structural injury. The ubiquous protein annexin A1 (ANXA1) has potent anti-inflammatory effects and protects against ischemia/reperfusion injury. We investigated the effects of exogenous ANXA1 treatment in an experimental model of acute FK nephrotoxicity. Methods: Munich-Wistar rats received a low-salt diet for one week and were randomized to treatment with ANXA1 (Ac2-26 peptide 0.5 mg/Kg/day s.c.), FK (6 mg/Kg/day p.o.), association (FK+ANXA1) and vehicles (1 mL/Kg/day) for seven days. Results: FK induced a significant decrease in the glomerular filtration rate, renal blood flow and a significant increase in the renal vascular resistance. In addition, FK caused extensive acute tubule-interstitial damage and increase of anti-inflammatory ANXA1 expression in renal tissue. Exogenous ANXA1 treatment reduced FK-induced tubular dilatation and macrophage infiltration. We observed, for the first time, that FK augmented ANXA1 expression in renal tissue. Conclusion: Exogeneous ANXA1 treatment protected partially against FK-induced tubular injury, macrophage infiltration and may be targeted in renal intervention strategies. (AU)