Enteral supplementation with ornithine alpha ketoglutarate improves the early adaptive response to resection.

Abstract

Background-Polyamine synthesis or uptake, or both, might be an important event that initiates the adaptive hyperplasia seen in the intestinal remnant after partial small bowel resection. Aim-The ability ofan enteral diet supplemented with the ornithine salt: ornithine a ketoglutarate (OKG), a precursor for polyamine synthesis, to modulate the adaptive response of the remnant ileum after jejunectomy was evaluated. Methods-Adult Wistar rats underwent a resection of the proximal 50% of the small intestine. Controls underwent a single transection. The rats were fed intragastrically with a nutritive mixture supplemented either with casein hydrolysate or with OKG (1 g/kg). The isoenergetic and isonitrogeneous diets was given continuously for seven days. Results-Villus and crypt hyperplasia was observed in the remnant ileum compared with transected controls. OKG supplementation started after resection a further increase in villus height. After resection, OKG supplementation increased significantly the putrescine content and the amount of ornithine decarboxylase mRNA. A twofold to threefold increase of sucrase activity was measured in the resected animals compared with the transected rats. In contrast, the amount of sucrase mRNA was significantly lower in the ileum of the resected rats and OKG supplementation initiated a further drop in the amount of sucrase mRNA without pronounced changes in enzyme activity. Conclusions-The adaptive hypertrophy seen after resection can be accelerated by supplementing the diet with ornithine (OKG) a precursor of polyamine synthesis. In the remnant ileum, the reduced amount of sucrase mRNA, despite the increased level of sucrase activity, suggests a post-translational control of sucrase expression. (Gut 1997; 40: 67-72)

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model

“…4) compared with sham animals (group A). The reported changes are consistent with results of our previous studies [23][24][25] and with data presented by other investigators [9][10][11]. Following parenteral arginine administration (group C), SBS rats demonstrated a significant decrease in ileal overall bowel (43±4 vs. 51±2, p<0.05) and mucosal weight (14±2 vs. 18±1, p<0.05), mucosal DNA content in jejunum (55±7 vs. 92±12 lg/cm/100 g, p<0.05) and protein content in ileum (30±6 vs. 51±6 lg/cm/100 g, p<0.05), villus height in jejunum (712±128 vs. 1009±64 lm, p<0.05) and ileum (493±58 vs. 622±65 lm, p<0.05), and crypt depth in jejunum (167±2 vs. 235±25 lm, p<0.05) and ileum (159±13 vs. 201±14 lm, p<0.05) compared with SBS-untreated animals (group B).…”

“…Hebiguchi and colleagues reported that arginine supplementation in the diet resulted in a significant increase in ileal villus height compared with control animals; they concluded that arginine stimulates mucosal growth after massive bowel resection, probably through stimulation of growth hormone secretion [13]. Arginine may also influence intestinal adaptation through production of polyamine [9] or NO. There is growing evidence suggesting the central importance of apoptosis in controlling the enterocyte mass following massive small bowel resection.…”

Effects of Parenteral Arginine Supplementation on the Intestinal Adaptive Response after Massive Small Bowel Resection in the Rat

“…Moreover, blocking of polyamine synthesis results in inhibition of the adaptive response [3,4]. Finally, both intraluminal infusion of putrescine and enteral supplementation with the arginine-related compound ornithine-␣-ketoglutarate results in increased intestinal adaptation [5,6]. This may be mediated by conversion of ornithine into putrescine, catalyzed by ornithine decarboxylase (ODC; EC 4.1.1.17) [7,8].…”

Métabolisme et fonctions des polyamines

“…Le rôle des polyamines dans la trophicité intestinale est éga-lement illustré par les études sur l'adaptation intestinale suite à une résection ou une transplantation intestinale [8,10]. Après résection, il est observé une augmentation significative du contenu en polyamines de l'intestin résiduel.…”

“…Le blocage de l'ODC par la DFMO supprime cette augmentation et entraîne une suppression ou un ralentissement de la réponse adaptative évaluée par la mesure des hauteurs villositaires ou l'augmentation des activités hydrolasiques de la bordure en brosse des entérocytes. Inversement, le blocage de la DAO renforce la réponse adaptative intestinale [8].…”