title: Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats.
abstract: 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.
  
  
  CONCLUSIONS
  ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.
authors.affiliation: Post-Graduation Program in Morphology, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Leandro Pires
authors.initials: LP
authors.lastname: Araujo
authors.forename: Renata Ramos
authors.initials: RR
authors.lastname: Truzzi
authors.forename: Gloria Elisa Florido
authors.initials: GE
authors.lastname: Mendes
authors.forename: Marcus Alexandre Mendes
authors.initials: MA
authors.lastname: Luz
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Burdmann
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Oliani
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism / Q000627:therapeutic use*; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D010455:Peptides / Q000378:metabolism / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D017305:Annexin A1; D007166:Immunosuppressive Agents; D010455:Peptides; D020011:Protective Agents; D016212:Transforming Growth Factor beta; C096153:annexin A1 peptide (2-26); D016572:Cyclosporine
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