Arginine supplementation improves histone and acute-phase protein synthesis during gram-negative sepsis in the rat.
Mechanisms of nutrient alteration of hepatic protein synthesis during sepsis are unclear.  In vitro, arginine downregulates endotoxin-stimulated hepatocyte protein synthesis but in vivo effects are unknown.  This study evaluated the effects of supplemental arginine or glycine on fibrinogen (acute-phase protein), histone, albumin, and liver protein synthesis after Gram-negative sepsis in the rat.  Adult rats (225 g, n=36) were randomized to receive isonitrogenous isocaloric total parenteral nutrition supplemented with 264 mg of N per kilogram per day as either arginine or glycine.  On day 5, each group was further randomized to control or sepsis.  Sepsis was induced by injection of 8 x 10(7) Escherichia coli per 100 g body weight, and then a continuous infusion of [1-14C] leucine was started.  The rats were sacrificed 4 hours later.  The fractional protein synthesis rates (percent per day) of histone, fibrinogen, albumin, and liver were determined.  Supplemental arginine led to significantly increased histone (p < 0.05, analysis of variance) and fibrinogen (p < 0.01, analysis of variance) synthesis in the septic rats compared with all other groups.  Histone and albumin synthesis were also significantly increased (p < 0.05) in the arginine-supplemented control group compared with the glycine-supplemented control group.  Arginine supplementation during sepsis significantly increased (p < 0.05) albumin and liver protein synthesis compared with controls.  Histones which are involved in DNA synthesis and are rich in arginine may play a role in the host response to stress and sepsis.  These in vivo results appear to contradict hepatocyte-Kupffer cell coculture studies perhaps because of the hormonal and cytokine responses to nutrient substrate and acute septicemia.
León
P
P
Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia.
Redmond
H P
HP
Stein
T P
TP
Shou
J
J
Schluter
M D
MD
Kelly
C
C
Lanza-Jacoby
S
S
Daly
J M
JM
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D004927:Escherichia coli Infections; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis; D006657:Histones / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D010289:Parenteral Nutrition, Total; D014176:Protein Biosynthesis; D051381:Rats; D018805:Sepsis / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*
D000418:Albumins; D006657:Histones; D005340:Fibrinogen; D001120:Arginine