Arginine supplementation improves histone and acute-phase protein synthesis during gram-negative sepsis in the rat

• Published in: JPEN. Journal of parenteral and enteral nutrition Vol. 15; no. 5; p. 503
• Main Authors: León, P, Redmond, H P, Stein, T P, Shou, J, Schluter, M D, Kelly, C, Lanza-Jacoby, S, Daly, J M
• Format: Journal Article
• Language: English
• Published: United States 01.09.1991
• Subjects: Albumins - biosynthesis; Animals; Arginine - administration & dosage; Arginine - therapeutic use; Escherichia coli Infections; Female; Fibrinogen - biosynthesis; Histones - biosynthesis; Liver - metabolism; Parenteral Nutrition, Total; Protein Biosynthesis; Rats; Sepsis - metabolism; Sepsis - microbiology; Sepsis - therapy
• ISSN: 0148-6071
• DOI: 10.1177/0148607191015005503

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.