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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Renal Replacement Therapy, Vol 9, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 2059-1381
DOI: 10.1186/s41100-023-00508-w
Popis: 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
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