A diet containing glycine improves survival in endotoxin shock in
the rat.
Ikejima, Kenichi, Yuji Iimuro, Donald T. Forman, and Ronald G.
Thurman.
Laboratory of Hepatobiology and Toxicology, Department of
Pharmacology, and Department of Pathology, University of North
Carolina at Chapel Hill, Chapel Hill, NC 27599-7365
APStracts 3:0011G, 1996.
In this study, we investigated the effects of a glycine-containing
diet (5 %) on mortality and liver injury due to intravenous injection
of endotoxin (E. coli LPS) in Sprague-Dawley rats in vivo. Fifty
percent of the rats fed control diet died within 24 hr after an
intravenous injection of LPS (10 mg/kg), whereas glycine feeding
totally prevented mortality and markedly reduced an LPS-induced
elevation of serum transaminase levels, hepatic necrosis and lung
injury. The elevation in serum TNF-[alpha] due to LPS was also
blunted and delayed significantly by glycine feeding. In a 2-hit
model (hepatic ischemia/reperfusion and injection of sublethal LPS),
all rats fed control diet died, while 83% of glycine-fed animals
survived with a significant reduction in transaminases and improved
liver and lung histology. LPS elevated intracellular Ca2+ ([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.
Received 18 September 1995; accepted in final form 19 December
1995.
APS Manuscript Number G415-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96