Aminoguanidine blocks intestinal diamine oxidase (DAO) activity and enhances the intestinal adaptive response to resection in the rat.
The aim of this study was to assess the effect inhibiting diamine oxidase (DAO) activity on intestinal adaptation after 80% proximal small bowel resection in the rat. Aminoguanidine (AG), a DAO inhibitor, was administered subcutaneously (25 mg kg-1 day-1) to rats for 11 days after small bowel transection (n = 6) or resection (n = 6). Two additional groups of animals (n = 6) served as transection or resection controls and received normal saline subcutaneously for the same period. On day 12 after operation, the animals were sacrificed, mucosal homogenates prepared from the ileal remnants (or from the control ileum), analysed for DAO and ornithine decarboxylase (ODC) activities, and the concentrations of the polyamines putrescine, spermidine, spermine, and the indices of mucosal mass (wet weight, protein and DNA) measured. The results were expressed both per unit length intestine and per milligram mucosal DNA. AG treatment completely inhibited DAO activity in both the transection control and resected rats. In the AG-treated resection group, inhibition of DAO activity was accompanied by increases (p less than 0.005) in all three indices of mucosal mass (wet weight, protein and DNA per centimetre intestine), putrescine concentrations (p less than 0.05) and ODC activity per centimetre intestine (p less than 0.001) when compared with the saline-treated resection controls. The results of this study suggest that inhibition of the putrescine-degrading enzyme, DAO, enhances the adaptive response to intestinal resection. Therefore, DAO may play a major role in regulating adaptive intestinal mucosal growth. Furthermore, inhibition of DAO activity could be important therapeutically in patients with the short bowel syndrome.
Rokkas
T
T
Division of Medicine, UMDS of Guy's Hospital, London, UK.
Vaja
S
S
Murphy
G M
GM
Dowling
R H
RH
D000222:Adaptation, Physiological / Q000502:physiology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007082:Ileum / Q000201:enzymology* / Q000502:physiology / Q000601:surgery; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015317:Biogenic Polyamines; D006146:Guanidines; D006631:Amine Oxidase (Copper-Containing); D009955:Ornithine Decarboxylase; C004479:pimagedine