A diet containing glycine improves survival in endotoxin shock in the rat

Am J Physiol. 1996 Jul;271(1 Pt 1):G97-103. doi: 10.1152/ajpgi.1996.271.1.G97.


In this study, we investigated the effects of a glycine-containing diet (5%) on mortality and liver injury due to intravenous injection of endotoxin [Escherichia coli lipopolysaccharide (LPS)] in Sprague-Dawley rats in vivo. Fifty percent of the rats fed control diet died within 24 h after an intravenous injection of LPS (10 mg/kg), whereas feeding the rats glycine totally prevented mortality and markedly reduced an LPS-induced elevation of serum transaminase levels, hepatic necrosis, and lung injury. The elevation in serum tumor necrosis factor-alpha (TNF-alpha) due to LPS was also blunted and delayed significantly by glycine feeding. In a two-hit model (hepatic ischemia-reperfusion and injection of sublethal LPS), all rats fed control diet died, whereas 83% of glycine-fed animals survived with a significant reduction in transaminases and improved liver and lung histology. LPS elevated intracellular Ca2+ concentration ([Ca2+]i) in cultured Kupffer cells, an effect blocked almost completely by glycine. Glycine most likely reduces injury and mortality by preventing the LPS-induced elevation of [Ca2+]i in Kupffer cells, thereby minimizing toxic eicosanoid and cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animal Feed
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Glycine / administration & dosage
  • Glycine / blood
  • Glycine / pharmacology*
  • Ischemia / complications
  • Kupffer Cells / metabolism
  • Lipopolysaccharides / pharmacology
  • Liver / drug effects
  • Liver / pathology
  • Liver Circulation
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Septic / complications
  • Shock, Septic / mortality*
  • Survival Analysis
  • Transaminases / blood
  • Tumor Necrosis Factor-alpha / analysis


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Transaminases
  • Calcium
  • Glycine