PREVENTIVE ADMINISTRATION OF ORNITHINE ALPHA-KETOGLUTARATE IMPROVES INTESTINAL MUCOSAL REPAIR AFTER TRANSIENT ISCHEMIA IN RATS

Objectives: To investigate whether the preventive enteral administrati on of a polyamine precursor, such as ornithine alpha-ketoglutarate (OK G), has a beneficial effect on the repair process of the intestinal mu cosa after transient mesenteric vascular occlusion. Design: A controll ed laboratory study. Setting: A research laboratory facility at the Re search Institute for Digestive Cancer. Subjects: Male Wistar rats, wei ghing 330 to 350 g, housed individually in plastic cages under standar dized conditions (23 degrees 6, 73 degrees F, 60% relative humidity, 1 2-hr light and 12-hr dark cycles). Interventions: Intragastrically, 1. 5 or 17 hrs before surgery, animals received either distilled water (w ater group), or an amino acid solution of either OKG (1 g/kg) or L-lys ine (0.68 g/kg) in distilled water under isonitrogenous conditions. In testinal ischemia was produced in anesthetized rats by occluding the s uperior mesenteric artery for 90 mins with a microbulldog clamp. At th e end of the ischemic period, the clamp was removed, allowing reperfus ion, and the abdomen was closed. Measurements and Main Results: At 0, 4, and 24 hrs after ischemia/reperfusion, the midjejuno-ileum was rese cted. Intestinal morphology, polyamine content, and hydrolase activiti es were determined. In all groups at the end of the ischemic period, t he villi were dismantled with preservation of the crypts. Rats treated with OKG exhibited a restoration of short villi by 4 hrs after ischem ia/reperfusion. In other groups, the villi remained extensively denude d. By 24 hrs, only rats treated with OKG showed a complete recovery of normal mucosal architecture. The amount of the polyamines, putrescine , and spermidine were significantly enhanced by 4 hrs after ischemia/r eperfusion in the mucosa of rats treated with OKG, as compared with th e two other groups, At a functional level, sucrase and aminopeptidase activities remained significantly higher by 4 hrs of ischemia/reperfus ion in rats treated with OKG as compared with rats receiving water or lysine. By 24 hrs, hydrolase activities were normalized in rats treate d with OKG, whereas an important deficit in hydrolase activities remai ned in rats receiving either water or lysine. Conclusions: OKG adminis tration to rats did not prevent ischemic damage of the intestinal muco sa, but it accelerated the repair of the mucosa during reperfusion. OK G favored the restitution of normal villus architecture and the functi onal recovery of the intestinal mucosa. We hypothesized that OKG trigg ered metabolites might mediate the restitution process and contribute to the healing of the intestinal mucosa by minimizing cell injury and by promoting the replacement of injured cells.