Effect of oxidative stress and endotoxin on human serum albumin in brain-dead organ donors.
Albumin, among other molecules, binds and detoxifies endotoxin in healthy people. Oxidative stress leads to protein oxidation and thus to the impaired binding properties of albumin. This property, in combination with increased gut permeability, leads to the appearance of endotoxin in the systemic circulation and to impaired organ function. We hypothesize that these processes occur in the serum of brain-dead organ donors. Endotoxin was determined with an adapted Limulus amoebocyte lysate assay. The albumin fractions and binding capacity were determined by high-performance liquid chromatography (HPLC). FlowCytomix (eBioscience, San Diego, Calif) was used to determine the cytokine levels. Carbonylated proteins (CPs) and myeloperoxidase (MPO) were measured by an enzyme-linked immunosorbent assay (ELISA). Eighty-four brain-dead organ donors were enrolled and categorized by the duration of intensive care unit (ICU) stay. The albumin-binding capacity for dansylsarcosine was reduced in brain-dead patients compared with controls. Endotoxin positivity in 16.7% of donors was associated with decreased binding capacity in donors and worse survival of recipients. The CP and MPO levels of organ donors were significantly higher than in healthy controls. The durations of ICU stay increased albumin oxidation. In addition, interleukin-6 (IL-6), IL-8, IL-10, and IL-1β levels were increased in patients, whereas the interferon-γ (IFN-γ) levels were within the normal range. We conclude that oxidative stress and systemic endotoxemia are present in brain-dead organ donors, which might affect recipient survival. High endotoxin levels might be caused by increased gut permeability and decreased binding capacity of albumin influenced not just by higher albumin oxidation.
Division of Transplantation Surgery, Medical University of Graz, Graz, Austria.
Bettina
B
Leber
Vanessa
V
Stadlbauer
Philipp
P
Stiegler
Stefanie
S
Stanzer
Ursula
U
Mayrhauser
Sonja
S
Koestenbauer
Barbara
B
Leopold
Michael
M
Sereinigg
Andreas
A
Puntschart
Tatjana
T
Stojakovic
Karl-Heinz
KH
Tscheliessnigg
Karl
K
Oettl
D000293:Adolescent; D000328:Adult; D000368:Aged; D001926:Brain Death / Q000097:blood*; D003422:Critical Care; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood; D011485:Protein Binding; D050050:Protein Carbonylation; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism*; D013997:Time Factors; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting; D057170:Translational Research, Biomedical; D019737:Transplants; D055815:Young Adult
D016207:Cytokines; D004731:Endotoxins; D007378:Interleukins; D012709:Serum Albumin; D009195:Peroxidase