title: Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice.
abstract: OBJECTIVE
  There is substantial experimental evidence that the amino acid glycine may have a role in protecting tissues against insults such as ischemia, hypoxia and reperfusion. Our aim was to investigate the ability of the amino acid glycine to prevent hepatic damage induced by injection of lipopolysaccharide and d-galactosamine (d-Gal), to modulate pro- and anti-inflammatory cytokine levels, and to improve survival.
  
  
  METHODS
  Mice were challenged with an intraperitoneal injection of d-Gal (16 mg/mouse) and lipopolysaccharide (LPS, 1 microg/mouse). The intervention group also received an intraperitoneal injection of glycine (150 mg/kg) in two doses: 24 h before and just after LPS challenge. Serum cytokine levels were measured 2 h after challenge, and liver enzymes and histology were determined 16 h after LPS. Separate groups of mice received the same treatment and the survival rate was determined 24 h and ten days after endotoxin administration. In in vitro experiments, cultured mononuclear cells were stimulated by LPS, and TNF-alpha and IL-10 secretion were measured, in the presence or absence of glycine.
  
  
  RESULTS
  In the glycine-treated mice, the serum levels of liver enzymes and TNF-alpha, the histologic necroinflammation score and the mortality rate were significantly reduced compared to control mice (P<0.001). Serum IL-10 levels in the glycine-treated mice were increased (P<0.01). In vitro studies in cultured lymphocytes isolated from either normal or glycine pretreated mice, demonstrated a significant and dose-dependent inhibition of LPS-induced TNF-alpha secretion and increase in IL-10 response after treatment with glycine (P<0.01). In conclusion, glycine reduces hepatic damage and improves survival rate in this mouse model of endotoxemia. The protective effect of glycine is associated with modulation of TNF-alpha and IL-10 secretion.
authors.affiliation: Department of Gastroenterology, The E Wolfson Medical Center, Holon, Israel. rbruck@wolfson.gov.il
authors.forename: Rafael
authors.initials: R
authors.lastname: Bruck
authors.forename: Joram
authors.initials: J
authors.lastname: Wardi
authors.forename: Hussein
authors.initials: H
authors.lastname: Aeed
authors.forename: Yona
authors.initials: Y
authors.lastname: Avni
authors.forename: Haim
authors.initials: H
authors.lastname: Shirin
authors.forename: Ilana
authors.initials: I
authors.lastname: Avinoach
authors.forename: Mark
authors.initials: M
authors.lastname: Shahmurov
authors.forename: Rami
authors.initials: R
authors.lastname: Hershkoviz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D004926:Escherichia coli / Q000276:immunology; D005688:Galactosamine / Q000633:toxicity; D005998:Glycine / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D008070:Lipopolysaccharides; D005688:Galactosamine; D005998:Glycine