Protective effect of glutamine on the main and adjacent organs damaged by ischemia-reperfusion in rats

Abstract

Intestinal ischemia and reperfusion (I/R) causes cellular and tissue damage to the intestine and remote organs such as the liver. Increased production of ROS and nitric oxide and dysregulation of cytoprotective enzymes may be involved in intestinal I/R. The aim was to evaluate the protective effects of glutamine on the intestine and liver of rats with intestinal I/R injury. Twenty male Wistar rats (300 g) were divided into four groups: sham-operated (SO), glutamine + SO (G + SO), I/R, and glutamine + I/R (G + I/R). Occlusion of the SMA for 30 min was followed by 15-min reperfusion. Glutamine (25 mg/kg/day) was administered once daily 24 and 48 h before I/R induction. Blood and tissue of were collected for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, histopathological analysis, immunohistochemistry of IL-1β and TNF-α, thiobarbituric acid reactive substance (TBARS) and nitric oxide, Nrf2/keap1, superoxide dismutase (SOD), NADPH quinone oxidoreductase1 (NQO1), inducible nitric oxide synthase (iNOS), heat shock protein (HSP70), glucose-regulated protein 78 (GRP78), and activating transcription factor 6 (ATF-6) by western blot. Statistic analysis by ANOVA-Student-Newman-Keuls test (mean ± SE) significantly was p < 0.05. Tissue damage, AST, ALT, IL-1β, TNF-α, TBARS, NO, Keap1, iNOS, GRP78, and ATF-6 expression were significantly lower in the G + I/R group as compared to the I/R group. Expression of Nrf2, SOD, NQO1, and HSP70, was significantly higher in the G + I/R group as compared to I/R group. Pre-treatment with glutamine provided protection against oxidative damage in the intestine and liver in an experimental model of intestinal I/R.

Glutamine protects intestine against ischemia-reperfusion injury by alleviating endoplasmic reticulum stress induced apoptosis in rats

“…Lots of clinical practice and experimental research indicate that the position of glutamine as a kind of important intestinal mucosa protectant cannot be replaced, as it plays a significant role in maintaining intestinal mucosa completeness, lowering intestinal mucosa permeability, enhancing intestinal immunity, reducing bacteria translocation and preventing intestinal mucosa cell apoptosis. All these mechanisms have been confirmed by our previous study [6][7][8] . A recent study suggests that glutamine treatment attenuates ER stress and apoptosis in TNBSinduced colitis 9 .…”

Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress

“…Actually, our proteomic investigation did not allow us to find enzymes involved in ammonia production. However, the increased GLUL expression was not rescued at normal levels after MUT reintroduction, thus convincing that this aspect, corroborated by recent findings revealing that the treatment with glutamine protected from ROS and oxidative damage [36], needs further investigation. Thus, GLUL upregulation could be induced for protecting cells from ammonia accumulation via incorporation in glutamine and, at the same time, providing protection against oxidative damage.…”

Protective action of glutamine in rats with severe acute liver failure

“…Under physiological conditions, Nrf2 is stores in the cytoplasm in inactivated form, bound to Kelch-like ECH-associated protein 1 (Keap1). Under stress conditions, Nrf2 dissociates Keap1 and is translocated to the nucleus, where it promotes expression of cytoprotective target genes, such as NADPH quinone oxidoreductase1 (NQO1), antioxidant enzymes, and phase-II detoxification enzymes such as glutathione S-transferase (GST)[5,14-16].…”

“…The inflammatory process leads to parenchymal damage, which progresses to fibrosis, liver cancer, and, occasionally, SALF[17]. Metabolites of hepatotoxic drugs bind to a toll-like receptor 4 (TLR4) complex that activates nuclear factor kappa B (NFκB), triggering the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and modulation of anti-inflammatory cytokines such as IL-10[12,14,17,18]. Furthermore, it can stimulate production of the enzymes cyclooxygenase-2 (COX-2) and iNOS, both of which act as inflammatory mediators[19].…”