Methionine dietary supplementation potentiates ionizing radiation-induced gastrointestinal syndrome.

Methionine is an essential amino acid needed for a variety of processes in living organisms. Ionizing radiation depletes tissue methionine concentrations and leads to the loss of DNA methylation and decreased synthesis of glutathione. In this study, we aimed to investigate the effects of methionine dietary supplementation in CBA/CaJ mice after exposure to doses ranging from 3 to 8.5 Gy of 137Cs of total body irradiation. We report that mice fed a methionine-supplemented diet (MSD; 19.5 vs. 6.5 mg/kg in a methionine-adequate diet, MAD) developed acute radiation toxicity at doses as low as 3 Gy. Partial body irradiation performed with hindlimb shielding resulted in a 50% mortality rate in MSD-fed mice exposed to 8.5 Gy, suggesting prevalence of radiation-induced gastrointestinal syndrome in the development of acute radiation toxicity. Analysis of the intestinal microbiome demonstrated shifts in the gut ecology, observed along with the development of leaky gut syndrome and bacterial translocation into the liver. Normal gut physiology impairment was facilitated by alterations in the one-carbon metabolism pathway and was exhibited as decreases in circulating citrulline levels mirrored by decreased intestinal mucosal surface area and the number of surviving crypts. In conclusion, we demonstrate that a relevant excess of methionine dietary intake exacerbates the detrimental effects of exposure to ionizing radiation in the small intestine.NEW & NOTEWORTHY Methionine supplementation, instead of an anticipated health-promoting effect, sensitizes mice to gastrointestinal radiation syndrome. Mechanistically, excess of methionine negatively affects intestinal ecology, leading to a cascade of physiological, biochemical, and molecular alterations that impair normal gut response to a clinically relevant genotoxic stressor. These findings speak toward increasing the role of registered dietitians during cancer therapy and the necessity of a solid scientific background behind the sales of dietary supplements and claims regarding their benefits.

Supplemental dietary arginine accelerates intestinal mucosal regeneration and enhances bacterial clearance following radiation enteritis in rats.

BACKGROUND: Arginine is a dibasic amino acid with significant metabolic and immunologic, effects especially in trauma and stress situations. Arginine supplementation has been shown to promote wound healing and improve immune system. We designed a study to evaluate the effects of supplemental dietary arginine on intestinal mucosal recovery and bacterial translocation and bacterial clearance after induction of radiation injury in rats. METHODS: Twenty-one male Sprague-Dawley rats were subjected to a single dose of 1100 rads of abdominal X radiation. Rats were divided into three groups; the first group received diet enriched with 2% arginine, the second group with 4% arginine, and the third group with isonitrogenous 4% glycine. Rats were sacrificed 7 days after the radiation. Blood was drawn for arginine levels and mesenteric lymph nodes were harvested for quantitative aerobic and anaerobic cultures. Segments of ileum and jejunum were evaluated for villous height, number of villi per centimeter of intestine, and the number of mucous cells per villous. RESULTS AND CONCLUSIONS: Arginine is absorbed reliably from the gut following oral administration. Dietary 4% arginine supplementation enhanced bacterial clearance from mesenteric lymph nodes compared to 2% arginine and 4% glycine supplemented diet following radiation enteritis in rats. Four percent arginine resulted in clear improvement in intestinal mucosal recovery when compared to 2% arginine and 4% glycine after abdominal irradiation in rats.

[Selective decontamination of the intestine and total gnotobiologic isolation in treatment of mice with acute radiation sickness]. / Primenenie selektivnoi dekontaminatsii kishechnika i obshchei gnotobiologicheskoi izoliatsii pri lechenii myshei s ostroi luchevoi bolezn'iu.

Comparative study of ciprofloxacin, pefloxacin and amikacin showed that ciprofloxacin and pefloxacin had a selective action on the intestinal microflora of conventional mice. Amikacin induced inhibition not only of the opportunistic bacteria but also of the representatives of the indigenous microflora. The use of the drugs in combination with total gnotobiological isolation in treatment of experimental radiation sickness provided an increase in survival of the irradiated animals, the more so as ciprofloxacin was used.

[The effect of new antimicrobial preparations used in combination with complete gnotobiotic isolation on the survivability and intestinal microflora of total-body irradiated mice]. / Izuchenie vliianiia novykh antimikrobnykh preparatov, primeniaemykh v komplekse s obshchei gnotobiologicheskoi izoliatsiei, na vyzhivaemost' i mikrofloru kishechnika total'no obluchennykh myshei.

The aim of these investigations was the study of the effect of different antimicrobial preparations on the survival rate and intestinal microflora of mice with experimental acute radiation sickness. These investigations revealed that the survival rate of the animals increased 3.1 times with the use of Supramycin, 2.4 times with the use of Tacef and 1.6 times with the use of Spizef and Pen-bristol. The study of the influence of these preparations on the intestinal microflora revealed that Spizef not only decreased the number of opportunistic microorganisms, but also led to a sharp drop in the level of lactobacteria. The use of Pen-bristol and Tacef led to practically complete elimination of enterobacteria enterococci, staphylococci, as well as lactobacteria. Supramycin essentially suppressed the number of opportunistic microorganisms and did not affect the level of lactobacteria. This was probably the cause of the highest effectiveness of Supramycin in comparison with Tacef, Spizef and Pen-bristol.

[The effect of a preparation made from Solco lactobacteria on the survival rate and intestinal microflora of irradiated animals]. / Izuchenie vliianiia preparata iz laktobakterii "Solko" na vyzhivaemost' i mikrofloru kishechnika u obluchennykh zhivotnykh.

Lactobacillus acidophilus strain Lat 11/83 Solco has been used for the normalization of intestinal microflora in experimental post-irradiation intestinal dysbacteriosis in mice. The results of these experiments indicate that live Solco lactobacteria, introduced intragastrically, facilitate the enhancement of the survival rate of irradiated animals and the normalization of microflora in their gastrointestinal tract. The strain can be used as bacterial preparation for the regulation of intestinal microbiocenosis.

[Effect of the combined use of antibiotic-resistant bifidobacteria and the corresponding antibiotics on the survivability of irradiated mice]. / Vliianie sochetannogo primeneniia antibiotikoustoichivykh bifidobakterii i sootvetstvuiushchikh antibiotikov na vyzhivaemost obluchennykh myshei.

The combined administration of antibiotic-resistant bifidobacterial strains and the corresponding antibiotics (ampicillin, gentamycin or kanamycin) leads to a greater increase in the survival rate of irradiated mice than the administration of antibiotics only and is a promising method for the treatment of post-irradiation intestinal dysbacteriosis.