Renal Replacement Therapy (Nov 2023)

High-dose atorvastatin reduces oxidative stress of ischemia/reperfusion injury after isogeneic kidney transplantation in rats: in vivo, preclinical, case–control, open-label study

  • Giacomo Cusumano,
  • Edoardo Cola,
  • Gionata Spagnoletti,
  • Anna Severino,
  • Simona Giubilato,
  • Egidio Stigliano,
  • Maria Emiliana Caristo,
  • Gisella Vischini,
  • Giovanna Liuzzo,
  • Maria Paola Salerno,
  • Filippo Crea,
  • Jacopo Romagnoli

DOI
https://doi.org/10.1186/s41100-023-00508-w
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 10

Abstract

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Abstract Background Renal ischemia/reperfusion injury is an unavoidable event in transplantation in which free radical-mediated injury determines release of pro-inflammatory cytokines and activation of innate immunity. In addition to their cholesterol-lowering action, statins have shown dose-dependent pleiotropic effects on inflammatory pathways and oxidative stress. We investigated the effects of high-dose atorvastatin (atorvastatin 40 mg/kg) in preventing ischemia/reperfusion injury in an animal model of kidney transplant. Methods Forty female rats underwent left nephrectomy and orthotopic autotransplantation. Animals were divided in four groups: A = Transplant only; B = high-dose atorvastatin + Transplant; C = right nephrectomy + Transplant; D = high-dose atorvastatin + right nephrectomy + Transplant. Bilateral nephrectomy was performed 24 h post-transplant. Oxidative stress was assessed measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activity on renal tissue; ischemia/reperfusion injury was also evaluated by histology. Donor pre-treatment with high-dose atorvastatin improved oxidative stress. Results MDA levels were lower in group B versus A (p = 0.002) and D (p = 0.004). High-dose atorvastatin pre-treated rats displayed higher GPx activity in group B versus A (p = 0.009) and D (p = 0.005). SOD scavenger activity was also higher in group B versus A (p < 0.001) D (p < 0.001) and C (p = 0.003). MPO activity was lower in group B versus A (p = 0.02), C (p = 0.007) and D (p = 0.03). Histology revealed significantly lower rate of intratubular casts and luminal congestion in Group D versus C (p = 0.02 and p = 0.008, respectively). Conclusions High-dose atorvastatin pre-treatment reduces oxidative stress and inflammation in a model of kidney transplant in the rat.

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