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


CONCLUSIONS
Exogenous ANXA1 treatment partially protected against FK-induced tubular injury and macrophage infiltration, and may be targeted in renal intervention strategies.
Araujo
Leandro P
LP
Federal University of São Paulo, Brazil.
Truzzi
Renata R
RR
Mendes
Gloria E
GE
Luz
Marcus A M
MA
Burdmann
Emmanuel A
EA
Oliani
Sonia M
SM
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000633:toxicity*
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D016559:Tacrolimus