Promotion of intestinal carcinogenesis by dietary methionine.

The metabolism of the polyamines spermidine and spermine is known to be enhanced in rapidly proliferating cells. Methionine is a precursor of the aminopropyl moieties of these amines. Therefore, it was of interest to study the effects of a methionine supplemented diet on polyamine metabolism and preneoplastic changes occurring in the intestinal tract of rats treated with the chemical carcinogen azoxymethane (AOM). Adult Wistar rats received 15 mg AOM/kg body wt (i.p.) once each week for 2 weeks. Thereafter, the rats were randomly divided into two groups and received controlled isoenergetic diets containing the same amount of folate, choline and vitamin B12 during 12 weeks: one group was kept on a standard diet; the other was fed the same diet, except that 1% L-methionine was added at the expense of carbohydrates. After 12 weeks, the administration of the methionine-supplemented diet stimulated the turnover rate of ileal epithelial cells, indicating enhanced crypt cell proliferation. Furthermore, in this group, a 2-fold increase in the number of aberrant hyperproliferative crypts and the appearance of tumors was observed in the colon. These effects were accompanied by the increased formation of spermidine and spermine due to the enhancement of S-adenosylmethionine decarboxylase activity and by the upregulation of Cdx-1, a homeobox gene with oncogenic potentials. The experimental data do not support the view of a chemopreventive effect of dietary methionine supplementation on intestinal carcinogenesis in rats, even at an early phase of preneoplastic development, but rather suggest that methionine promotes intestinal carcinogenesis.

Functional and metabolic changes in intestinal mucosa of rats after enteral administration of ornithine alpha-ketoglutarate salt.

BACKGROUND: Ornithine alpha-ketoglutarate salt efficiently improves the nutritional status of protein-depleted patients. Our aim was to explore the effects of ornithine alpha-ketoglutarate supplementation on intestinal physiology in healthy animals. METHODS: Rats were given a nutritive mixture supplemented with ornithine alpha-ketoglutarate (1 g.kg-1 per day) by enteral route for 7 days. Controls received the diet supplemented with casein acid hydrolysate under isoenergetic and isonitrogenous conditions. RESULTS: An adaptive hyperplasia of the villi and an increase in the brush-border hydrolase activities were observed in rats receiving ornithine alpha-ketoglutarate. Because of the high ornithine aminotransferase activity, ornithine alpha-ketoglutarate-derived ornithine was extensively transaminated with a concomitant enhancement of ornithine decarboxylation. Surprisingly, with glutamate and putrescine, the products of ornithine transamination and decarboxylation, gamma-aminobutyric acid accumulated (10-fold to 16-fold) dramatically in the intestinal mucosa of rats treated with ornithine alpha-ketoglutarate. Because gamma-aminobutyric acid formation was completely prevented by the diamine oxidase inhibitor aminoguanidine but was not modified after inactivation of ornithine aminotransferase by 5-fluoromethylornithine, it is evident that gamma-aminobutyric acid is formed in the mucosa from ornithine via putrescine as an intermediate. CONCLUSIONS: It is assumed that enhanced gamma-aminobutyric acid formation in the intestinal mucosa by ornithine alpha-ketoglutarate treatment might be of physiologic importance in the regulatory processes of cell growth and differentiation.

Dietary calcium supplementation, blood pressure, and intestinal calcium absorption.

This study investigated the potential intestinal mechanism in the blood pressure-lowering effect of dietary calcium supplement. Adult Wistar rats received, through a gastrotomy cannula, either 5 or 30 mg elemental calcium.d-1 x 100 g BW-1 for 10 days. At day 11, mean arterial pressure was measured directly in anesthetized animals and calcium absorption determined using an in situ measurement technique of calcium absorption. An intestinal loop (duodenum and proximal jejunum) was perfused both by the intraluminal and the vascular routes. A solution containing 45Ca was perfused intraluminally and the 45Ca appearing in the venous effluent was determined to estimate calcium absorption. Oral calcium supplementation caused intestinal calcium uptake by the isolated loop to increase almost twofold. It also resulted in an 18% increase in mesenteric blood flow. The mean arterial pressure was decreased in calcium supplemented rats compared with control rats (87 +/- 5 vs. 78 +/- 5 mmHg; p < 0.05). These findings could indicate that the passive part of intestinal calcium transport increases in response to dietary calcium supplement. This improvement may participate in the blood pressure-lowering effect of a high calcium diet.

Development of a technique for in situ studies of calcium absorption in the intestine of rats.

The aim of the present study was to develop (feasibility, reliability, reproducibility) a technique for the in situ measurement of intestinal calcium absorption in the rat. An intestinal loop (duodenum+proximal jejunum) was perfused both by the intraluminal and vascular routes. A solution of NaCl 155 mM and CaCl2 1.25 mM containing 45Ca was perfused intraluminally at a flow rate of 0.2 ml/min and the 45Ca appearing in the venous effluent was determined to estimate calcium absorption. This technique was used to study the effect of a 10-day period of calcium supplementation on calcium absorption. The animals received enterally either 5 or 30 mg/day per kg BW. The results showed that intestinal calcium transport was enhanced when rats were given the calcium supplement for 10 days prior to the experiment (99.3 +/- 2.5 (n = 5) versus 36.6 +/- 3.6 (n = 5) nmol/min per kg BW, P < 0.001). This study indicates that dietary calcium supplement enhances calcium absorption probably by increasing the passive transport of calcium in the small intestine.