α-Lipoic Acid Protects Against Ischemia-Reperfusion Injury in Simultaneous Kidney-Pancreas Transplantation.
BACKGROUND
Multiple factors have been implicated in the process of ischemia-reperfusion injury (IRI) in organ transplantation. Among these factors, oxidative damage seems to initiate the injury. α-lipoic acid (ALA) is a potent antioxidant that is used in patients with diabetic polyneuropathy. The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI.


METHODS
Twenty-six patients were included in the following groups: (i) untreated control; (ii) donor and recipient (DR) ALA-treated, in which ALA was administered both to the deceased donor and to the recipients; and (iii) recipient ALA-treated group. The expression of inflammatory genes, as observed in biopsies taken at the end of surgery, as well as the serum cytokines, secretory leukocyte protease inhibitor, regenerating islet-derived protein 3β/pancreatitis-associated protein, amylase, lipase, glucose, and creatinine levels were quantified as markers of organ function.


RESULTS
The DR group showed high levels of TGFβ and low levels of C3 and TNFα in the kidneys, whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies. Decreases in serum IL-8, IL-6, secretory leukocyte protease inhibitor, and regenerating islet-derived protein 3 β/pancreatitis-associated protein were observed after surgery in the DR group. Serum lipase and amylase were lower in the DR group than in the control and recipient groups. Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group.


CONCLUSIONS
These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis.
1 CEFYBO-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 2 Instituto de Nefrología de Buenos Aires, Buenos Aires, Argentina. 3 Centre de Recherche en Cancérologie de Marseille (CRCM), Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France. 4 GADOR SA, Buenos Aires, Argentina.
Nella
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Ambrosi
Victoria
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Arrosagaray
Diego
D
Guerrieri
Pablo D
PD
Uva
Jorgelina
J
Petroni
Mónica Buonpensiere
MB
Herrera
Juan L
JL
Iovanna
Luis
L
León
Claudio
C
Incardona
H Eduardo
HE
Chuluyan
Domingo H
DH
Casadei
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001118:Argentina; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D016035:Pancreas Transplantation / Q000009:adverse effects; D010182:Pancreatic Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D000073718:Pancreatitis-Associated Proteins; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D008063:Thioctic Acid / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D008063:Thioctic Acid