Functional and Metabolic Changes in Intestinal Mucosa of Rats After Enteral Administration of Ornithine α-Ketoglutarate Salt

Abstract

Background: Ornithine α-ketoglutarate salt efficiently improves the nutritional status of protein-depleted patients. Our aim was to explore the effects of ornithine α-ketoglutarate supplementation on intestinal physiology in healthy animals. Methods: Rats were given a nutritive mixture supplemented with ornithine α-ketoglutarate (1 g·kg^-1 per day) by enteral route for 7 days. Controls received the diet supplemented with casein acid hydrolysate under isoenergetic and isonitrogenous conditions. Results: An adaptive hyperplasia of the villi and an increase in the brush-border hydrolase activities were observed in rats receiving ornithine α-ketoglutarate. Because of the high ornithine aminotransferase activity, ornithine α-ketoglutarate-derived ornithine was extensively transaminated with a concomitant enhancement of ornithine decarboxylation. Surprisingly, with glutamate and putrescine, the products of ornithine transamination and decarboxylation, γ-aminobutyric acid accumulated (10-fold to 16-fold) dramatically in the intestinal mucosa of rats treated with ornithine α-ketoglutarate. Because γ-aminobutyric acid formation was completely prevented by the diamine oxidase inhibitor aminoguanidine but was not modified after inactivation of ornithine aminotransferase by 5-fluoromethylornithine, it is evident that γ-aminobutyric acid is formed in the mucosa from ornithine via putrescine as an intermediate. Conclusions: It is assumed that enhanced γ-aminobutyric acid formation in the intestinal mucosa by ornithine α-ketoglutarate treatment might be of physiologic importance in the regulatory processes of cell growth and differentiation. (Journal of Parenteral and Enteral Nutrition 19:145-150, 1995)