Abstracts
1997 Digestive Disease Week

Somatostatin analogue predisposes enterocytes to apoptosis.

JS Thompson. Surgical Service, Omaha VA Medical Center; and Department of Surgery, University of Nebraska Medical Center, Omaha, NE.

Introduction. The somatostatin analogue octreotide impairs intestinal regeneration and the adaptive response to intestinal resection and other stimuli. These effects are mediated, in part, by inhibition of enterocyte migration and proliferation. The aim of this study was to determine if octreotide promotes enterocyte apoptosis.

Methods. Twelve New Zealand rabbits underwent patch enteroplasty in the distal ileum to stimulate the mucosa. Six animals received 100 mg subcutaneous octreotide daily and six served as controls. Normal ileal mucosa adjacent to the patch was evaluated at 7 days for villus height, crypt cell production rate (CCPR), and in situ end labeling of DNA fragmentation using biotinylated nucleotides. Fragmentation was graded on a scale of 1 to 3: 1 - indicating minimal staining and <= 2 condensed cells/villus; 2 - diffuse light staining and <= 5 condensed cells/villus; and 3 - diffuse staining with >5 intensely stained enterocytes on the villus with chromatin condensation.

Results. Octreotide treated animals had similar villus height (338±49 vs. 382±43 µm) and CCPR (8.7±1.4 vs. 7.3±2.1 cells/hour) compared to controls. Mean DNA fragmentation was significantly greater in octreotide treated animals (p<0.5 Mann Whitney rank test). Staining was greater and cells with chromatin condensation more prevalent near the tip of the villus. Fragmentation scores ranged from 1.0-1.5 in controls and 1.1-2.65 in treated animals. Staining of enterocytes was quite heterogenous, however, among the villi of individual treated animals. One (16%) control animal had at least one grade 3 villus compared to five (84%) treated animals (p<0.05). There was no correlation between either CCPR or DNA fragmentation and mean villus height.

Conclusions. (1) Octreotide treatment is associated with increased DNA fragmentation in enterocytes, suggesting endonuclease activation. (2) Predisposition to apoptosis may play a role in octreotide effects on intestinal regeneration and adaptation. (3) Overall, there is not a direct correlation between villus height and either enterocyte production or apoptosis.