ABSTRACT
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.
Subject(s)
Amine Oxidase (Copper-Containing)/antagonists & inhibitors , Azo Compounds/toxicity , Azoxymethane/toxicity , Intestines/drug effects , Amine Oxidase (Copper-Containing)/metabolism , Animals , Colon/drug effects , Colon/enzymology , Duodenum/drug effects , Duodenum/enzymology , In Vitro Techniques , Intestines/enzymology , Male , Rats , Rats, Inbred F344ABSTRACT
UNLABELLED: In the intestinal mucosa, diamine oxidase probably is involved in a feedback regulation mechanism for the termination of proliferation. This was proven by a considerable promotion of large bowel tumors induced by diamine oxidase inhibition in a rat model. Carcinogenesis was accompanied by characteristic alterations in mucosal diamine oxidase activity. In large bowel cancer patients similar changes in intestinal diamine oxidase activity had been observed as in the animal model. CONCLUSION: Events entailing a reduction of diamine oxidase activity are suspicious for large bowel cancer promotion under experimental and clinical conditions.
Subject(s)
Amine Oxidase (Copper-Containing)/antagonists & inhibitors , Antineoplastic Agents/therapeutic use , Intestinal Neoplasms/chemically induced , Adult , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/pharmacology , Cell Division/drug effects , Disease Models, Animal , Female , Humans , Intestinal Mucosa/pathology , Intestinal Neoplasms/drug therapy , Intestinal Neoplasms/enzymology , Male , Middle Aged , Rats , Rats, Inbred F344ABSTRACT
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.
Subject(s)
Amine Oxidase (Copper-Containing)/metabolism , Intestine, Small/surgery , Suture Techniques , Animals , Intestinal Mucosa/injuries , Intestine, Small/enzymology , Male , Rats , Rats, Inbred F344 , Time Factors , Wound HealingABSTRACT
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.
