alpha-Lipoic Acid Protects the Ischemia Reperfusion Injury in Human Kidney-Pancreas Transplantation

GUERRIERI DIEGO; PETRONI JORGELINA; AMIANO NICOLÁS; ARROSAGARAY VICTORIA; CHULUYAN EDUARDO; CASADEI DOMINGO; INCARDONA CLAUDIO

Congreso; American Transplant Congress; 2013

Ischemia reperfusion injury (IRI) is a coordinated process leading to delayed graft function (DGF) and reduced long-term graft survival of the transplanted organ. *Objective and methods:* The aim of the present study was to determine the effect of a-lipoic acid in patients undergoing pancreatic-kidney transplant evaluating functional recovery of graft and biochemical markers of ischemia reperfusion injury. The study included 11 kidney-pancreas transplant patients (4 males, 5 females). 600 mg of alpha lipoic acid was administered to the deceased donor at the time of ablation and to the organ recipient. From the 11 patients, 4 received the a-lipoic acid treatment. Three blood samples were obtained: at the beginning of the surgery (and after the a-lipoic acid administration); the second blood samples were obtained at the end of surgery and after the unclamping procedure; and the last sample was taken 12 h after surgery. Furthermore, a kidney and pancreas biopsies were taken at the end of the surgery. Real-time PCR analysis was performed on biopsies for TGFb, TNFa, IL-10, C3, HMOX and IL-6 gene expression. Human inflammatory cytokines (TNFa, IL-1b, IL-10, IL-8, IL-6 and IL-12p79) were measured by using a BD Cytometric Bead Array. *Results*: The analysis of the biopsies showed that HMOX, C3 and IL-6 genes expression were increased in kidney biopsies and HMOX, C3 and TGFb were increased in pancreas biopsies. The only gene that was downregulated in both organs biopsies was IL-10. The analysis of serum inflammatory cytokines showed that the serum levels of TNFa, IL-1b, IL-6 and IL-12p70 were almost undetectable for all samples at all the times analyzed. However, a 40 fold increased in the levels of IL-8 was observed immediately after the surgery in control patients, while only a 1.1 fold increased was observed in the serum of a-lipoic acid treated patients. Furthermore, a-lipoic acid treated patients showed a slightly lower serum level of IL-10 compared to control patients. Differences in serum levels of IL-8 and IL-10 were not observed in the blood samples obtained 12 h after surgery. *Conclusions:* The treatment with a-lipoic acid to kidney and pancreas transplant patients decreased certain serum pro-inflammatory cytokines, increased the expression of protective factors, such as HMOX in the graft and therefore protects from the IRI.