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-Lipoic Acid Protects the Ischemia Reperfusion Injury in Human Kidney-Pancreas Transplantation
GUERRIERI DIEGO; PETRONI JORGELINA; AMIANO NICOLAS; ARROSAGARAY VICTORIA; UVA PABLO; CHULUYAN EDUARDO; CASADEI DOMINGO; INCARDONA CLAUDIO
Congreso; American transplat congress 2013; 2013
ASTS, TTS, AST
INTRODUCTION: Ischemia reperfusion injury (IRI) is a coordinated process leading to delayed graft function (DGF) and reduced long-term graft survival of the transplanted organ. Therefore, there is special interest in testing agents that reduced the IRI. a-lipoic acid (ALA) is a fat and water-soluble potent antioxidant. It has the ability to regenerate other factors such as vitamins C and E in addition to raising glutathione intracellularly. Furthermore, ALA functions as free radical scavengers. ALA is proposed to mitigate the development of diabetic sensorimotor polyneuropathy by addressing reactive oxygen and nitrogen species that are overproduced in the setting of diabetes mellitus. Intravenous and oral forms of ALA are approved for treatment of diabetic sensorimotor polyneuropathy in some countries. Patients that received kidney-pancreas transplantation in order to ameliorate insulin-dependent type 1 diabetes may be treated with ALA. Therefore, we decided to evaluate the effect of ALA on IRI in pancreatic-kidney transplant patients. OBJECTIVE AND METHODS:The aim of the present study was to determine the effect of a-lipoic acid (ALA) in patients undergoing pancreatic-kidney transplant evaluating functional recovery of graft and biochemical markers of ischemia reperfusion injury. The study included 18 kidney-pancreas transplant patients (9 males and 9 females). Alpha lipoic acid (600 mg) was administered to the deceased donor at the time of ablation and to the recipients during the surgical procedure. From the 18 patients, 8 received the a-lipoic acid treatment. Several blood samples were obtained at different time points: i) at the beginning of the surgery (and after the a-lipoic acid administration to the recepient); ii) at the end of surgery and after the unclamping procedure; iii) 12 h after surgery; and iv) every one or two day after the transplant for at least 18 days. Furthermore, a kidney and pancreas biopsies were taken at the end of the surgery. Real-time PCR analysis was performed on biopsies for TGF-b, TNF-a, IL-10, C3, HMOX and IL-6 gene expression.Human inflammatory cytokines (TNF-a, IL-1b, IL-10, IL-8, IL-6 and IL-12p79) were measured by using a BD Cytometric Bead Array. The measurements of serum amylase, lipase, glycemia and creatinine levels were performed as markers of organ rejection for at least 18 days post-surgery. RESULTS:The analysis of the biopsies showed that HMOX, C3 and IL-6 genes expression were increased in kidney biopsies and HMOX, C3 and IRAK2 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 TNF-a, 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. The analysis of measurement of serum lipase showed that the mean lipase values of a-lipoic treated patients were lower than controls patients (P < 0.001). Statistically significant differences were also observed in amylase values when the analysis was performed on the first six days after the transplant. AUC analyses of lipase levels showed a total peak area of 8747 and 4373 for control and a-lipoic acid treated patients. AUC analyses of lipase levels in blood and drainage fluid were 8747 and 4373, for control and a-lipoic acid treated patients, respectively while AUC of amylase levels were 1205 and 713, respectively. The difference between the groups was not statistically significant for glycemia. On the contrary, the analysis of measurement of creatinine serum showed that the mean creatinine values of a-lipoic treated patients were higher than controls patients (P < 0.01). CONCLUSIONS:The treatment with a-lipoic acid to donors and kidney and pancreas transplant patients decreased serum IL-8 and IL-10, increased the expression of protective factors, such as HMOX in the graft and decreased the postoperative amylase and lipase values in blood therefore protects from the IRI, at least in pancreas.