L-glutamine-induced heme oxygenase-1 protects small intestine from warm ischemia and reperfusion injury in the rat
Yasuhara, M.
Hokkaido Journal of Medical Science 76(1): 21-34
2001
ISSN/ISBN: 0367-6102 PMID: 11235209 Document Number: 540279
Although it is considered that L-Glutamine (L-Gln) supplementation improves gut morphology and survival in animal models such as radiation and drug-induced enterocolitis, the mechanisms underlying are far from being established. Recently, Gln has been reported to give protection against stress in in vitro intestinal epithelial cell lines through the induction of heat shock proteins (HSPs). This study is designed to examine whether L-Gln may induce cytoprotective molecules such as heme oxygenase-1/HSP32 (HO-1) and reduced glutathione (GSH) in in vivo intestinal tissues, and to clarify whether these molecules may play a role in warm ischemia and reperfusion (I/R) injury. We measured the releases of serotonin and tumor necrosis factor-alpha (TNF-alpha), and graft survival as viability assays following reperfusion of warm ischemically injured intestinal grafts. The substantial expression of HO-1 after L-Gln administration was observed in villous epithelial cells, crypts and muscular layers, and peaked at 6 h, while that of the control group pretreated with lactated Ringer (LR) solution was observed throughout tissues to be slightly similar to those of fresh untreated tissues. Tissue GSH contents slightly increased 24 h after administration and were less reduced through the periods of I/R than those of the LR group. Releases of serotonin and TNF-alpha in L-Gln group were attenuated during the brief periods of warm ischemia, compared with those in the LR group. A significant graft survival rate was also observed between both groups (6/6 of L-Gln group vs. 1/6 of LR group; p < 0.05). In conclusion, the protective effects of L-Gln in small intestines against warm I/R injury were considered to be in part mediated by up-regulation of molecules such as HO-1 and GSH via cellular antioxidant activity. Thus, L-Gln pretreatment may represent an innovative approach to the prevention of complex I/R injury.