A role for HO-1 in renal function impairment in animals subjected to ischemic and reperfusion injury and treated with immunosuppressive drugs

Introduction. Ischemia/reperfusion injury (IRI) represents the single major antigenin-dependent factor implicated in pathogenesis of chronic graft dysfunction. Tacrolimus is a calcineurin inhibitor, which has been suggested to be helpful in cyclosporine-related chronic toxicity. Rapamycin has antiproliferative properties that may impair renal regeneration after IRI. Therefore, immunosuppressive drugs might impair renal graft outcome in those organs suffering IRI.Material and Methods. C57B1/6 male mice subjected to 45 minutes of renal pedicle ligation were reperfused for 24 hours. Mice were treated with rapamycin, cyclosporine, or tacrolimus. Blood and renal tissue samples were collected at 24 hours after IRL Urea levels were measured. Heme Oxygenase 1 (HO-1) gene transcript was amplified by a real-time polymerase chain reaction technique.Results. Animals treated with cyclosporine and subjected to IRI showed impaired renal function that peaked at 24 hours. Additional pretreatment with rapamycin produced even more impairment of renal function, when compared with controls. However, tacrolimus pretreatment was associated with a better renal outcome. HO-1 expression was upregulated after IRI by 2.6 arbitrary units at 24 hours. Rapamycin showed worse impairment of renal function.Conclusion. Tacrolimus was not associated with worsening renal function when compared with animals just subjected to IRL Upregulation of HO-1 may be an attractive approach to limit graft injury.Universidade Federal de São Paulo, Div Nephrol, Lab Expt & Clin Immunol, BR-04023062 São Paulo, BrazilUniv Triangulo Mineiro, Dept Pathol, Uberaba, MG, BrazilUniv São Paulo, Dept Immunol, Transplantat Immunobiol Lab, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Lab Expt & Clin Immunol, BR-04023062 São Paulo, BrazilWeb of Scienc