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

Abstract:

BACKGROUND:Tacrolimus (FK) is currently widely used in transplant immunosuppression and the treatment of autoimmune diseases. However, FK induces nephrotoxicity which is characterized by functional and structural renal injury. The ubiquitous 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 1 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 7 days. RESULTS:FK induced a significant decrease in glomerular filtration rate and renal blood flow, and a significant increase in renal vascular resistance. In addition, FK caused extensive acute tubule-interstitial damage and an increase in anti-inflammatory ANXA1 expression in renal tissue. Exogenous ANXA1 treatment reduced FK-induced tubular dilatation and macrophage infiltration. For the first time, we observed that FK augmented ANXA1 expression in renal tissue. CONCLUSION:Exogenous ANXA1 treatment partially protected against FK-induced tubular injury and macrophage infiltration, and may be targeted in renal intervention strategies.

journal_name

Am J Nephrol

authors

Araujo LP,Truzzi RR,Mendes GE,Luz MA,Burdmann EA,Oliani SM

doi

10.1159/000309756

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

527-33

issue

6

eissn

0250-8095

issn

1421-9670

pii

000309756

journal_volume

31

pub_type

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