Decreased Ischemia Reperfusion Injury in a Syngeneic Rat Model by the Administration of Rabbit anti rat Thymocyte Immunoglobulin to Donors
CICORA FEDERICO; ROBERTI JAVIER; LAUSADA NATALIA; GONZALEZ PEDRO; GUERRIERI DIEGO; STRINGA PABLO; CICORA PAOLA; VAZQUEZ DANIELA; PALTI GUSTAVO; CHULUYAN EDUARDO; RAIMONDI CLEMENTE
WILEY-BLACKWELL PUBLISHING, INC
Ischemia reperfusion injury (IRI), during renal transplantation, is a major cause of early graft dysfunction, predisposing the patient to acute rejection and decreased graft survival in the long term. Polyclonal anti thymocyte immunoglobulins (ATGs) are used to prevent and treat acute rejection after organ transplantation. To determine whether ATG attenuated IRI, we used an experimental renal transplantation model of isogenic rats. We administered rabbit anti-rat thymocyte immunoglobulin (rATG) to donors and evaluated biochemical and anatomopathological parameters: urea and creatinine levels, necrosis and apoptosis and components intervening in the leukocyte extravasation to the inflamed tissue as adhesion molecules (ICAM-1), cytokines (IL-6, IL-21, IL-17, TNF-alpha, TGF-beta1), chemokines (Cxcl1 and Cxcl3) and a molecule related to tubular dysfunction (KIM-1). Urea showed a significant difference between control and treatment kidneys (p<0.001). We observed a significant difference between the two groups in creatinine levels (p<0.001), significantly lower levels of necrosis and apoptosis in treatment group and a reduced in situ expression of TNF-alpha, IL-6, IL-21, TGF-beta1, KIM-1, Caspase 8 (p<0.001). Bcl2 and HO1 were upregulated in situ in treatment group (p<0.001). Our results show that in kidneys from donors treated with rATG there appeared decreased urea and creatinine levels and reduced necrosis and apoptosis.