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.

Soybean oil, blackcurrant seed oil, medium-chain triglycerides, and plasma phospholipid fatty acids of stressed patients.

Thirty-six adult severe head injury and cerebral stroke patients in four intensive-care units were randomized to receive one of three enteral diets for 21 days. These diets, which supplied 45% of calories from fat, differed only in lipid composition. Diet A was comprised of 100% soybean oil, diet B contained a 50:50 (wt/wt) mixture of soybean oil and medium-chain triglycerides (MCTs), and diet C contained 42.5% MCT, 50% soybean oil, and 7.5% blackcurrant seed oils. Plasma phosphatidylcholine and fatty acid composition of plasma total phospholipids were determined before initiating treatment (day 0) and weekly throughout the study. Results indicated that at the start of the study, all patients had low linoleic acid (18:2 omega 6) levels compared with healthy subjects. Emulsion A disturbed the balance between several fatty acids of the omega 6 series, as exemplified by the significant increase in 18:2 omega 6 proportions. In contrast, both emulsions B and C introduced a less-pronounced rise in 18:2 omega 6 associated for emulsion C with a significant increase in dihomo-gamma-linolenic acid (20:3 omega 6) and docosapentaenoic acid (22:5 omega 3) in plasma phospholipids. Furthermore, 18:3 omega 6 change was significantly different between groups A and C and that of 20:3 omega 6 between group A and both groups B and C. Throughout the study, arachidonic acid (20:4 omega 6) exhibited remarkable steady-state levels regardless of the diet. This study shows that providing the injured body with high amounts of 18:2 omega 6 does not lead to high levels of its upper derivatives in plasma phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Composition of phospholipid fatty acids in red blood cell membranes of patients in intensive care units: effects of different intakes of soybean oil, medium-chain triglycerides, and black-currant seed oil.

Fatty acid composition of phospholipids in red blood cell membranes was studied in 32 severely head-injured or cerebral stroke patients receiving enteral nutrition for 3 weeks. During this study the effects of three diets differing only by their lipid composition were investigated. The daily energy intake of each patient amounted to 2950 kilocalories, of which the lipid fraction represented 45.7%. Diet A contained only soybean oil, diet B consisted of a 50% soybean oil and 50% medium-chain triglycerides mixture, and diet C was an emulsion of 50% soybean oil, 42.5% medium-chain triglycerides, and 7.5% black-currant seed oil. Our results showed no biochemical signs of fatty acid deficiency in red blood cell membranes for the patients at the beginning of the study, after a comparison with a control group of 20 healthy adults. Inhibition of delta 6-desaturase activity on linoleic acid (C18:2 omega 6) after diet A was suggested by an increase of linoleic acid without a corresponding increase of dihomo-gamma-linolenic acid (C20:3 omega 6). Replacing 50% of soybean oil by with medium-chain triglycerides (diet B) prevented this enzyme inhibition. Supply of black-currant seed oil rich in gamma-linolenic (C18:3 omega 6) and stearidonic (C18:4 omega 3) acids (diet C) induced significant increases of dihomo-gamma-linolenic and eicosapentaenoic (C20:5 omega 3) acids, without influencing arachidonic acid (C20:4 omega 6) levels. This balance was evaluated through the ratio (C20:3 omega 6 + C20:5 omega 3)/C20:4 omega 6.