Ornithine alpha-ketoglutarate modulates tissue protein metabolism in burn-injured rats.

Abstract

Enterally administered ornithine alpha-ketoglutarate (OKG) displays whole body anabolic and anticatabolic properties in trauma situations, especially after burn injury. The aim of this study was to get information about the anabolic effect of OKG at tissue level. Thirty-six male Wistar rats (95 +/- 7 g) were allocated to four groups. Eighteen rats were burned by water (20% body surface area). After a 24-h fast (day 0-day 1), rats were enterally refed for 48 h (day 1-day 3) by use of Osmolite as a low-calorie, low-nitrogen regimen supplemented with either 5 g OKG.kg-1.day-1 (B-OKG) or an equivalent amount of nitrogen in the form of glycine (B-Gly). Nonburned pair-fed controls treated with glycine (C-Gly) and healthy rats fed ad libitum were also studied. On day 3, protein synthesis rates (large dose method), free glutamine concentrations, and total protein content were assessed in tissues. Myofibrillar degradation was assessed by measuring urinary 3-methylhistidine excretion daily from day 0 to day 3. With regard to tissue protein synthesis rates, we demonstrate for the first time that OKG displays anabolic properties in the jejunum [fractional synthesis rate (FSR) in %/day, ad libitum = 101.9 +/- 4.0; C-Gly = 84.7 +/- 3.1, P < 0.01 vs. ad libitum; B-Gly = 84.5 +/- 1.6, P < 0.01 vs. ad libitum; B-OKG = 97.5 +/- 3.2, P < 0.05 vs. C-Gly and B-Gly] as well as in the liver (FSR in %/day, ad libitum = 75.9 +/- 3.7; C-Gly = 53.2 +/- 3.8, P < 0.01 vs. ad libitum; B-Gly = 70.2 +/- 2.0, P < 0.01 vs. C-Gly; B-OKG = 98.7 +/- 4.6, P < 0.01 vs. ad libitum, C-Gly and B-Gly), the latter having previously been observed in vitro. Furthermore, we confirm that OKG inhibits myofibrillar degradation, counteracts the trauma-induced fall of muscle glutamine pool, and induces an increase in glutamine concentration in the jejunum.