Katharina Effenberger-Neidnicht1, Johannes Jägers2, Rabea Verhaegh2, Herbert de Groot2. 1. Institute of Physiological Chemistry, University Hospital Essen, Germany. Electronic address: katharina.effenberger-neidnicht@uni-due.de. 2. Institute of Physiological Chemistry, University Hospital Essen, Germany.
Abstract
BACKGROUND: Glycine is well known to protect the intestine against ischemia-reperfusion injury and during mechanical manipulation. Here, we studied whether glycine protects the small intestine during endotoxemia, even without being the site of the infection. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was infused at a rate of 1 mg/kg × h over a period of 7 h (subacute endotoxemia) in male Wistar rats. Glycine (single dose: 50 mg/kg × 15 min) was applied intravenously at 180 and 270 min after the beginning of the LPS infusion. Systemic parameters were periodically determined. The small intestine was analyzed for macroscopic (hemorrhages) and histopathologic changes (hematoxylin and eosin staining), and markers of inflammation (myeloperoxidase activity). RESULTS: Glycine neither decreased mortality nor beneficially affected vital parameters (e.g., mean arterial blood pressure and breathing rate), electrolytes, blood gases including pH and base excess, and plasma parameters of tissue injury such as lactate concentration, hemolysis, and aminotransferases activities during experimental endotoxemia. It, however, specifically diminished the LPS-induced small intestinal injury, as indicated by less intestinal accumulation of blood, less intestinal hemorrhages, and reduced intestinal hemoglobin content. CONCLUSIONS: The present results demonstrate that glycine selectively protects the small intestine during subacute endotoxemia, even after manifestation of a severe systemic impairment. Because glycine is non-toxic at low doses, an administration of a moderate glycine dose (50-100 mg/kg) may be suitable to protect from intestinal damage during sepsis. Its true clinical potential, however, needs to be verified in further experimental studies and clinical trials.
BACKGROUND:Glycine is well known to protect the intestine against ischemia-reperfusion injury and during mechanical manipulation. Here, we studied whether glycine protects the small intestine during endotoxemia, even without being the site of the infection. MATERIALS AND METHODS:Lipopolysaccharide (LPS) was infused at a rate of 1 mg/kg × h over a period of 7 h (subacute endotoxemia) in male Wistar rats. Glycine (single dose: 50 mg/kg × 15 min) was applied intravenously at 180 and 270 min after the beginning of the LPS infusion. Systemic parameters were periodically determined. The small intestine was analyzed for macroscopic (hemorrhages) and histopathologic changes (hematoxylin and eosin staining), and markers of inflammation (myeloperoxidase activity). RESULTS:Glycine neither decreased mortality nor beneficially affected vital parameters (e.g., mean arterial blood pressure and breathing rate), electrolytes, blood gases including pH and base excess, and plasma parameters of tissue injury such as lactate concentration, hemolysis, and aminotransferases activities during experimental endotoxemia. It, however, specifically diminished the LPS-induced small intestinal injury, as indicated by less intestinal accumulation of blood, less intestinal hemorrhages, and reduced intestinal hemoglobin content. CONCLUSIONS: The present results demonstrate that glycine selectively protects the small intestine during subacute endotoxemia, even after manifestation of a severe systemic impairment. Because glycine is non-toxic at low doses, an administration of a moderate glycine dose (50-100 mg/kg) may be suitable to protect from intestinal damage during sepsis. Its true clinical potential, however, needs to be verified in further experimental studies and clinical trials.