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Arginine Supplementation Improves Histone and Acute-Phase Protein Synthesis During Gram-Negative Sepsis in the Rat

Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, Pennsylvania

H. Paul Redmond, F.R.C.S.I.

Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, Pennsylvania

T. Peter Stein, PH.D.

Department of Surgery, University of Medicine and Dentistry of New Jersey, Camden, New Jersey

Jian Shou, M.D.

Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, Pennsylvania

Margaret D. Schluter, B.S.

Department of Surgery, University of Medicine and Dentistry of New Jersey, Camden, New Jersey

Cathal Kelly, F.R.C.S.I.

Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, Pennsylvania

Susan Lanza-Jacoby, PH.D.

Department of Surgery, Thomas Jefferson Uniuersity, Philadelphia, Pennsylvania

John M. Daly, M.D., F.A.C.S.

Department of Surgery and the Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, Pennsylvania

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 10⁷ 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. (Journal of Parenteral and Enteral Nutrition 15:503-508, 1991)

Journal of Parenteral and Enteral Nutrition, Vol. 15, No. 5, 503-508 (1991)
DOI: 10.1177/0148607191015005503


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