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 antiinflammatory 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.

Ruta graveolens Protects Against Isoniazid/Rifampicin-Induced Nephrotoxicity through Modulation of Oxidative Stress and Inflammation

“…Studies presented evidence that nephrotoxicants could provoke an inflammatory response leading to organ injury [12,34]. The significantly elevated TNF-α reflects the degree of inflammation.…”

Aldosterone signaling through transient receptor potential melastatin 7 cation channel (TRPM7) and its α-kinase domain

“…Annexin-1, implicated in cell proliferation and differentiation, is characteristically associated with anti-inflammatory responses (45), mediated in part through inhibition of MAP kinases (46). In WT hTRPM7 cells, activation of annexin-1 as assessed by membrane translocation, was significantly increased by aldsoterone.…”

Activation of annexin A1 signalling in renal fibroblasts exerts antifibrotic effects

“…Previous localization studies for AnxA1 have shown strong expression of the protein in renal epithelia and an increased abundance in response to renal injury (McKanna et al 1992, Araujo et al 2012, Ka et al 2014. These studies also suggested interstitial expres-sion of AnxA1, but its cellular source and function were unknown.…”