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Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats

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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.

Conclusion

ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.

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Acknowledgments

Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (Grant 2008/01,048-9 to L.P.A.); Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPq (Grant 306,074/2007-9 to S.M.O. and 307,371/2006-9 to E.A.B.).

Conflict of interest

The authors have no competing financial interests to disclose in relation to this manuscript.

Author information

Authors and Affiliations

  1. Post-Graduation Program in Morphology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

    Leandro Pires Araujo & Sonia Maria Oliani

  2. Department of Biology, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), São Paulo State University (UNESP), Rua Cristovão Colombo 2265, São José do Rio Preto, CEP 15054-000, São Paulo, SP, Brazil

    Renata Ramos Truzzi & Sonia Maria Oliani

  3. Division of Nephrology, São José do Rio Preto Medical School, São Paulo, SP, Brazil

    Gloria Elisa Florido Mendes, Marcus Alexandre Mendes Luz & Emmanuel A. Burdmann

  4. Division of Nephrology, University of São Paulo Medical School, São Paulo, SP, Brazil

    Emmanuel A. Burdmann

Authors
  1. Leandro Pires Araujo
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  2. Renata Ramos Truzzi
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  3. Gloria Elisa Florido Mendes
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  4. Marcus Alexandre Mendes Luz
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  5. Emmanuel A. Burdmann
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  6. Sonia Maria Oliani
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Corresponding author

Correspondence to Sonia Maria Oliani.

Additional information

Responsible Editor: Michael Parnham.

Observation: S.M.O. and E.A.B. share senior authorship of this manuscript.

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Araujo, L.P., Truzzi, R.R., Mendes, G.E.F. et al. Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats. Inflamm. Res. 61, 189–196 (2012). https://doi.org/10.1007/s00011-011-0400-z

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  • DOI: https://doi.org/10.1007/s00011-011-0400-z

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