Drinking Water Of Mice Research Articles

Short Communication: Influence of Dietary Proteins on Production ofClostridium difficileToxins in Gnotobiotic Mice

Inoculation of a toxigenic Clostridium difficile strain in axenic mice fed a commercial rodent diet led to pseudomembranous caecitis and death of animals within 2 d. Different diets derived from the commercial one were prepared. A ‘Low protein diet’ afforded 74 per cent protection. Several additives were given in the drinking water of mice fed the protective ‘Low protein diet’. It was shown that some proteins and/or some small molecular weight compounds extracted from a brain-heart infusion prevented the protective effect provided by the ‘Low protein diet’. Toxin production was reduced in all protected mice, while it was similar to the control in dead mice. Keywords: Clostridium difficile ; Diet; Toxins.

The metabolism of malondialdehyde.

Interest in malondialdehyde (MDA) metabolism stems from its formation as a product of lipid peroxidation in the diet and in the tissues; its reactivity with functional groups of nucleic acid bases, proteins and phospholipids; its mutagenicity in bacteria, and its reported skin and liver carcinogenicity in animals. Administration of the Na enol salt of MDA in the drinking water of mice over a range of 0.1-10.0 micrograms/g/day for 12 mo produced dose-dependent hyperplastic and neoplastic changes in liver nuclei and increased mortality at the highest level but produced no gross hepatic tumors. Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%. [1,3-14C]MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine. Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis. Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA. N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the long-term depletion of reduced glutathione in mice administered l-buthionine- S,R-sulfoximine

Previous methods to deplete in vivo concentrations of reduced glutathione (GSH) have not been able to lower tissue GSH levels for extended periods, have been toxic, and can alter the metabolism of xenobiotics. A possible alternative to lower in vivo concentrations of GSH may be the use of buthionine- S,R-sulfoximine (BSO) in the drinking water of laboratory animals to inhibit the biosynthesis of GSH. It has been previously reported that 20 m m BSO in the drinking water given to mice was able to lower GSH levels in a variety of tissues after 15 days. In order to more fully characterize the in vivo depletion of GSH in tissues by ingestion of BSO and determine if this method would be suitable in studies requiring depressed levels of GSH for extended periods, we added different amounts of this agent to the drinking water given to mice for various times up to 28 days. We found that ingested BSO at the highest concentrtion used in drinking water (30 m m) was able to maximally lower GSH concentrations in mouse lungs, lung lavage fluid, liver, kidneys, and blood to 59.0 ± 3.6%, 35.0 ± 5.1%, 44.3 ± 1.5%, 69.5 ± 3.9%, and 70.0 ± 6.0% of control mice, respectively, for up to 28 days. These lowered concentrations of tissue GSH returned to control levels after mice were returned to untreated drinking water for 7 days. The potential toxicity of such treatments was also evaluated. Levels of alkaline phosphatase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase in lungs and lung lavage fluid, and total and differential cell counts from lung lavage fluid were not different between control and BSO-treated mice. This showed that BSO treatment did not produce indications of lung injury as measured by these biochemical parameters. Serum aspartyl transferase and γ-glutamyl transpeptidase activities were unaffected by the BSO treatments, indicating normal liver functions. Lung and liver cytochrome P-450 concentrations were also not different between controls and BSO-treated animals. Thus, BSO in the drinking water of mice was able to effectively lower in vivo levels of GSH without eliciting acute toxic responses.

The Administration of certain Chemotherapeutic Agents to Mice by Incorporation of the Chemical in the Drinking Water: An Evaluation of the Method

Summary and Conclusions The incorporation of certain chemicals in the drinking water of mice is a satisfactory and convenient means of administering chemotherapeutic agents. The blood levels resulting from this means of administration are as constant and run parallel with the levels resulting from incorporating the same compounds in the diet. Higher blood values have followed the intake of the water solution than of the diet mixture of the same concentration of drug. The method serves as a supplement to the drug-diet method, being a practical means of administering compounds in concentrations lower than can be adequately mixed with the food or compounds of such physical characteristics as do not lend themselves to incorporation in the diet.