FUNCTIONAL AND METABOLIC CHANGES IN INTESTINAL-MUCOSA OF RATS AFTER ENTERAL ADMINISTRATION OF ORNITHINE ALPHA-KETOGLUTARATE SALT

Background: Ornithine alpha-ketoglutarate salt efficiently improves th e nutritional status of protein-depleted patients. Our aim was to expl ore the effects of ornithine cu-ketoglutarate supplementation on intes tinal physiology in healthy animals. Methods: Rats were given a nutrit ive mixture supplemented with ornithine alpha-ketoglutarate (1 g . kg( -1) per day) by enteral route for 7 days. Controls received the diet s upplemented with casein acid hydrolysate under isoenergetic and isonit rogenous conditions. Results: An adaptive hyperplasia of the villi and an increase in the brush-border hydrolase activities were observed in rats receiving ornithine alpha-ketoglutarate. Because of the high orn ithine aminotransferase activity, ornithine alpha-ketoglutarate-derive d ornithine was extensively transaminated with a concomitant enhanceme nt of ornithine decarboxylation. Surprisingly, with glutamate and putr escine, the products of ornithine transamination and decarboxylation, gamma-aminobutyric acid accumulated (10-fold to 16-fold) dramatically in the intestinal mucosa of rats treated with ornithine alpha-ketoglut arate. Because gamma-aminobutyric acid formation was completely preven ted by the diamine oxidase inhibitor aminoguanidine but was not modifi ed after inactivation of ornithine aminotransferase by 5-fluoromethylo rnithine, it is evident that gamma-aminobutyric acid is formed in the mucosa from ornithine via putrescine as an intermediate. Conclusions: It is assumed that enhanced gamma-aminobutyric acid formation in the i ntestinal mucosa by ornithine alpha-ketoglutarate treatment might be o f physiologic importance in the regulatory processes of cell growth an d differentiation.