Ursodeoxycholic acid promotes intestinal adaptation in a cat model of short bowel syndrome.

The aim of this study was to assess the effect of ursodeoxycholic acid (UDCA) on the morphological and functional adaptive response of the jejunal remnant after massive intestinal resection in a cat model of short bowel syndrome (SBS). UDCA was administered to animals at a daily oral dose of 15 mg/kg for 6 weeks following a 85% jejunoileal resection. Resection alone caused extensive hyperplasia of jejunal mucosa, as evidenced by a significant increase in the weight of jejunal mucosa per unit length as well as by significant increases in DNA and protein concentration but no change in the protein/DNA ratio. Morphometric analysis using microscopy revealed no changes in jejunal mucosa thickness, jejunal crypt depth, villus height and villus surface area, although villus thickness was increased. The specific activities of jejunal sucrase and alkaline phosphatase were unaffected. UDCA treatment of resected animals, using doses that caused no toxicity, as evidenced by the absence of serum biochemistry abnormalities and histopathology, did not induce, compared to resection alone, any changes in mucosal cellularity and did not affect villus morphometry. On the other hand, UDCA administration increased crypt depth and, also, induced a profound increase in the specific activity of sucrase. UDCA improved diarrhoea, a core SBS symptom, reflected in a considerably reduced frequency of defaecation and improved form and texture of faeces. It is concluded that UDCA administration may enhance the natural adaptive response of the intestinal remnant following massive jejunoileal resection and may, thus, be beneficial in SBS treatment. 2011 The Authors Fundamental and Clinical Pharmacology. 2011 Société Française de Pharmacologie et de Thérapeutique.