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Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice
Author(s) -
Bruck Rafael,
Wardi Joram,
Aeed Hussein,
Avni Yona,
Shirin Haim,
Avinoach Ilana,
Shahmurov Mark,
Hershkoviz Rami
Publication year - 2003
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1034/j.1600-0676.2003.00839.x
Subject(s) - glycine , lipopolysaccharide , cytokine , intraperitoneal injection , tumor necrosis factor alpha , in vivo , medicine , secretion , galactosamine , endocrinology , in vitro , chemistry , pharmacology , amino acid , biology , biochemistry , microbiology and biotechnology , glucosamine
Background and aim: 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 μg/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‐α 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‐α, 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‐α 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‐α and IL‐10 secretion.