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O‐GlcNAc agonist treatment improves survival, reduces inflammation and organ damage 24 hours after trauma‐hemorrhage in rats
Author(s) -
Nöt Laszlo G,
Brocks Charlye A,
Marchase Richard B,
Chatham John C
Publication year - 2008
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.22.1_supplement.1227.5
Subject(s) - medicine , endocrinology , gastroenterology
We have shown that O‐GlcNAc (N‐acetyl‐glucosamine) agonists improve survival and reduce inflammatory response 2 hours after trauma‐hemorrhage (T‐H). The aim of the study was to evaluate the effects of O‐GlcNAc levels on survival, inflammation and organ damage 24 hours after T‐H. Fasted male rats were subjected to either sham surgery (SH) or (T‐H) and during the resuscitation phase received glucosamine (0.64g/kg, GN) or O‐(2‐Acetamido‐2‐deoxy‐D‐glucopyranosylidene)amino N‐phenyl Carbamate, (7mg/kg , PUGNAc) to increase O‐GlcNAc levels, or mannitol as control (CON). Survival was followed up for 24 hours. Both GN and PUGNAc increased 24 hours survival compared to controls (CON: 53%, GN: 85%, PUGNAc: 86%, logrank test, p<0.05). PUGNAc attenuated the T‐H induced increase in serum IL‐6 (SH: 8±6, CON: 181±36, PUGNAc: 42±22 pg/mL, p<0.05), ALT (SH: 89±19, CON: 297±56, PUGNAc: 125±21 IU, p<0.05), AST (SH: 503±218, CON: 1661±215, PUGNAc: 897±155 IU, p<0.05) and LDH (SH: 129±26, CON: 1499±311, PUGNAc: 357±99 IU, p<0.05); however, GN had no effect on serum parameters. PUGNAc but not GN maintained O‐GlcNAc levels in liver and lung and also attenuated the enhanced NF‐κB DNA binding and iNOS expression in the liver. These results demonstrate that increasing O‐GlcNAc levels with GN and PUGNAc improves 24 hr survival after T‐H; the different effects of GN and PUGNAc on tissue injury require further studies. NIH grant HL076165.