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Glutathione (GSH) Absolute Synthesis Rates (ASR) of Multiple Organs in a Pseudomonas aeroginosa (PM) induced Hyperdynamic Sepsis Pig Model
Author(s) -
Ten Have Gabriella A,
Engelen Marielle P,
Wolfe Robert R,
Deutz Nicolaas E
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.742.17
Subject(s) - glutathione , sepsis , jejunum , ileum , oxidative stress , glycine , medicine , gastroenterology , endocrinology , biology , chemistry , biochemistry , amino acid , enzyme
Rationale Sepsis is characterized by a severe redox imbalance. GSH plays a major role in the cellular defense against oxidative and nitrosative stress. It remains unclear whether the GSH defense capacity of tissues is affected differently at an early stage of severe sepsis. Therefore we measured the early response in GSH synthesis of the gut, muscle, liver, and lung in an acute live bacteria (PM) induced hyperdynamic severe sepsis catheterized pig model. Method We studied GSH‐ASR in 13 pigs (±25 kg) with intravenous PM induced hyperdynamic sepsis and 9 healthy controls, using primed, constant and continuous infusion of Glycine (1‐ 13 C) stable isotope in a conscious post‐absorptive state. Between 14 and 18 hours after start of the sepsis induction, we collected jejunal mucosa biopsies and erythrocytes, and at eighteen hours we obtained jejunum, jejunal mucosa scraping, ileum, liver, muscle and lung tissue. Enrichments of precursor pools and incorporated glycine in GSH were analyzed by LC‐MS/MS. Data are mean (SE) (in μmol/kg/h); ANOVA and unpaired t‐tests were done by GraphPad Prism. Results We found decreased values for GSH‐ASR 14 to18h after sepsis induction in jejunal mucosa biopsies (p=0.032) but not in erythrocytes. At t=18 h, we found lower ASR in sepsis in jejunum (37.3 (5.5) vs 23.7 (2.6), p=0.021) and jejunal mucosa scrapings (45.0 (6.2) vs. 28.9 (3.9), p=0.033). No changes in GSH‐ASR in ileum, liver and muscle were found but GSH‐ASR tended to be higher in the lung (20.2 (3.0) vs 26.9 (2.2), p=0.086). Conclusion In acute severe sepsis in the pig, the early defense capacity for oxidative stress is compromised in the mucosa of the jejunum, but not in the muscle, liver, lung, ileum and erythrocytes. We hypothesize that restoring the jejunal GSH defense capacity will attenuate the early sepsis induced gut dysfunction. Support or Funding Information This study was supported by NIH R01GM084447 and S10RR027047