After various kinds of intestinal mucosal injuries, whether by disease or by experiment, the diamine oxidase activity is reduced. Therefore, we studied the effect of surgical manipulations on the intestinal mucosa and diamine oxidase activity. The reaction of the gut on the insertion of sutures was a transient increase of the enzymic activity followed by reduction as soon as the mucosa started to gain weight. After a standardized pressure injury only a reduction of the diamine oxidase activity together with an enhancement of the mass of the intestinal wall was found. A hypothesis of a feed-back regulation of the diamine oxidase activity connected with mucosal proliferation is proposed.
In inflammatory diseases of the large bowel a reduced diamine oxidase activity was found which may be related to a reduced oxidative degradation of histamine. An experimental inhibition of diamine oxidase could therefore influence the large bowel histamine concentration. The diamine oxidase inhibitor aminoguanidine was administered to rats in a single dose of 100 mg/kg orally, i.v., or i.p. A rapid increase of the concentration of the drug in the large bowel was measured (half-life = 2-5 h). During chronic amino-guanidine administration (3 times/week, 100 mg/kg orally) the large bowel histamine increased by 30% on average. This may be sufficient for a proliferative stimulus of the intestinal mucosa. Previous reports of an increase of body weight of animals and of patients under aminoguanidine treatment could not be confirmed by our study.
Some mutagenic hydrazino compounds are also diamine oxidase inhibitors. Therefore, this interrelationship was studied for the intestinal carcinogen azoxymethane. In vitro, azoxymethane was a very weak inhibitor of rat intestinal diamine oxidase activity. In vivo, after subcutaneous injection of a single dose of azoxymethane, diamine oxidase activity was increased in the duodenum but was mainly inhibited in the colon. Intestinal diamine oxidase activity may then be influenced by regulatory processes induced by azoxymethane rather than by a direct effect.
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