Comparative study of glycine, alanine or casein as inert nitrogen sources in endotoxemic rats

Pharmacological effects of dietary amino acids (AA) and peptides must be co mpared to an isonitrogenous control that is as inert as possible. To establ ish a rationale for the choice of such a control, potential metabolic and n utritional effects of three currently used nitrogenous controls (glycine, a lanine, and casein) were evaluated in an endotoxemic rat model that has wel l-defined alterations in AA and protein metabolism. Five-week-old male Spra gue-Dawley rats (113 +/- 1 g) were randomly assigned to four groups and rec eived at d 0 an intraperitoneal injection of endotoxin (3 mg/kg). After wit hdrawal of food for 24 h, the rats were enterally refed for 48 h with a liq uid diet (Osmolite(R)) supplemented with 0.19 g N . kg(-1) . d(-1) in the f orm of glycine [lipopolysaccharide (LPS)-GLY group], alanine (LPS-ALA group ) or casein (LPS-CAS group). One group (LPS group) received only Osmolite(R ). Plasma, two skeletal muscles, the liver and the intestine were then remo ved. Body and tissue weights and tissue protein contents did not differ amo ng the four groups. Intestine histomorphometry showed no significant differ ence among groups. Jejunal hydrolase activities were significantly affected by the nitrogenous supplementations, but no effect was observed in the ile um. Only limited significant effects were observed on plasma and tissue-fre e AA concentrations, except for an accumulation of glycine in the plasma an d tissues from the LPS-GLY group, compared to other groups. Overall, wherea s glycine as a nitrogenous control should be used with care, either alanine or casein may be used as the "placebo," with the choice depending on the s tudy to be performed.