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.