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Biomedical subjects

I R Rowland

Publications and source records attributed to I R Rowland.

At least 91 records · Page 5Linked to original sources
PubMed1986

Enzyme activities of the hindgut microflora of laboratory animals and man.

A comparison was made in six species of animal (rat, mouse, hamster, guinea-pig, marmoset and man) of five enzyme activities associated with the hindgut microflora. Marked differences were found in the caecal activities of azoreductase, beta-glucosidase, beta-glucuronidase, nitrate reductase and nitroreductase in the four rodents, with no one species exhibiting consistently higher or lower enzyme activity. None of the laboratory animals, including the marmoset, provided an approximation of the enzyme profile associated with human faecal flora. The results indicate that it may be invalid to extrapolate the results of bacterial metabolic studies between closely related species, or from animals to man.

Animals↗
PubMed1985

Influence of dietary carrageenans on microbial biotransformation activities in the cecum of rodents and on gastrointestinal immune status in the rat.

Rats, mice, and hamsters were fed iota-carrageenan incorporated in a fiber-free, purified diet for 30 days, and the activities of a number of cecal microbial enzymes were determined in vitro. Carrageenan treatment produced cecal enlargement in all species, yet significantly decreased the concentration of bacteria per gram of cecal content. Azoreductase, beta-glucosidase, beta-glucuronidase, nitrate reductase, and nitroreductase activities per gram of cecal content were significantly decreased in the rat, although less consistent effects were found in these enzymes in the mouse and hamster. beta-Glucuronidase and nitrate reductase functions were increased per gram of cecal contents in the hamster. The total activity per cecum of certain of these enzymes was modified by the concomitant cecal enlargement, yet total nitroreductase activity was significantly decreased in all three rodent species. iota-Carrageenan significantly decreased the concentration of enterobacteria, staphylococci, streptococci, lactobacilli, facultative anaerobes, and the total microscopic count in the rat cecum, but did not exert any effect on bacterial viability in vitro. Although having no effect on biliary IgA antibody concentration, iota- and kappa- carrageenan when present at 50 g/kg diet increased the agglutination response of the IgA specific for the hindgut microflora.

Administration, Oral↗
PubMed1985

Activation of the food mutagens IQ and MeIQ by hepatic S9 fractions derived from various species.

The ability of hepatic S9 mixes derived from different rodent species (rat, mouse, Syrian and Chinese hamster) to activate the mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) was investigated using Salmonella typhimurium strain TA98. In general, the mutagenicity of IQ and MeIQ was greatest in the presence of S9 fractions from Swiss albino mice and least from fractions derived from Chinese hamsters. However, treatment of rats or hamsters with Aroclor 1254 had little or no effect on the activation of IQ or MeIQ to mutagens.

Animals↗
PubMed1985

Metabolic adaptation of rat faecal microflora to cyclamate in vitro.

Previous studies have demonstrated that the rat faecal microflora maintained in vitro under conditions of continuous flow possesses bacteriological and metabolic characteristics similar to those of the native bacterial population of the caecum. Addition of sodium cyclamate (75 mM) to the culture concurrent with the progressive dilution of the growth medium promoted metabolism of cyclamate to cyclohexylamine (sulphamatase activity) within 4 wk. The maximum formation of cyclohexylamine was attained in about 8 wk and was equivalent to a 2-3% molar conversion of cyclamate to cyclohexylamine. The recovery of viable cells from the culture and the total microscopic count decreased during the adaptation period, although the relative proportions of the major bacterial types remained unchanged. Concurrent with the increase in sulphamatase activity, other enzyme functions (as assessed by the API-zym system) decreased markedly. The ability to hydrolyse cyclamate to cyclohexylamine developed independently of other bacterial biotransformation enzymes in vitro, and was not associated with any gross taxonomic changes. These studies demonstrate the suitability of continuous culture systems for investigating the metabolic activity of the rat gut flora.

Adaptation, Biological↗
PubMed1985

Modification of rat caecal microbial biotransformation activities by dietary saccharin.

Male Sprague-Dawley rats were fed a purified fibre-free diet containing 5% (w/w) sodium saccharin for 4 weeks or 20 weeks and changes in caecal bacterial numbers and enzyme activities (endogenous ammonia production, beta-glucosidase, beta-glucuronidase, nitrate reductase, nitroreductase, aryl sulphatase) determined in vitro. Saccharin treatment gave marked caecal enlargement but had no effect on bacterial concentration at either treatment period, and significantly decreased beta-glucuronidase, nitrate reductase and sulphatase activities/g caecal contents. The incubation of a suspension of caecal contents from control rats with saccharin (75 mM) in vitro inhibited beta-glucuronidase and nitrate reductase activities, and ammonia production from endogenous substrates. Such changes may decrease the rate of formation of toxic bacterial products in the hindgut.

Ammonia↗
PubMed1985

The role of DNA-repair processes in N-nitrosopyrrolidine-induced mutagenesis.

The cytotoxic and mutagenic effects of increasing concentrations of N-nitrosopyrrolidine (NPYR) were studied using various DNA repair mutants of Escherichia coli together with rat-liver S9 activation system. Irrespective of which strain was used, the cytotoxic effects of NPYR were similar to those observed in the parent strain. Mutagenicity studies revealed that the uvrA- derivative was more mutable than its repair proficient parent. These observations suggest that NPYR reacts with DNA to generate bulky lesions, which although potentially mutagenic, do not contribute significantly to cell-killing. Subsequent experiments with the metabolic inhibitor SKF 525A revealed that this compound only partially inhibited the mutagenic activity of NPYR, suggesting that although hepatic mixed function oxidase enzymes may participate in NPYR activation other pathways of metabolism are also involved.

Animals↗
PubMed1985

The role of oral nitrate in the nitrosation of [14C]proline by conventional microflora and germ-free rats.

The urinary excretion of N-nitroso-L-[U-14C]proline by conventional microflora and germ free rats was used to assess the role of the gut bacteria and oral nitrate in the endogenous formation of N-nitroso compounds. The formation of nitrosoproline was qualitatively similar in conventional and germfree rats (equivalent to nitrosation of approximately 0.01-0.05% of the initial dose of [U-14C]proline) suggesting no involvement of the intestinal flora in this reaction. Furthermore, nitrosamino acid production was similar following the administration of nitrate and [U-14C]proline or [U-14C]proline alone, demonstrating no involvement of exogenous nitrate under the conditions of the experiment. Dietary contamination with nitrate/nitrite was negligible. The results are consistent with the suggestion that nitrate/nitrite reserves in the body are important in the formation of nitrosoproline in vivo.

Administration, Oral↗
PubMed1985

The influence of the host on expression of intestinal microbial enzyme activities involved in metabolism of foreign compounds.

The activities of four enzymes (beta-glucuronidase, nitrate reductase and nitroreductase) in selected intestinal bacteria (Escherichia coli, Clostridium sp., Streptococcus sp., Bacteroides sp. and Lactobacillus salivarius) were measured after growth in vitro and in vivo. The five strains differed in their activities with Clostridium sp. being the most active for beta-glucosidase, beta-glucuronidase and nitroreductase, and E. coli the most active producer of nitrate reductase. Enzyme activity in vivo tended to be higher than in vitro but there were instances where the comparative activities were reversed.

Animals↗
PubMed1985

The effect of diet on the mammalian gut flora and its metabolic activities.

The review will encompass the following points: A brief introduction to the role of the gut flora in the toxicology of ingested food components, contaminants, and additives, including known pathways of activation and detoxication of foreign compounds and the implication of the flora in enterohepatic circulation of xenobiotics. The advantages and disadvantages of the various methods of studying the gut flora (classical bacteriological techniques, metabolic and enzymological methods) will be critically discussed with special reference to their relevance to dietary, toxicological, and biochemical studies. Sources of nutrients available to the gut flora will be described including host products (mucus, sloughed mucosal cells, hormones, proteins) and exogenous nutrients derived from diet. An account of the problems involved in studies of dietary modification with special reference to the use of stock laboratory animal diets, purified diets, and human dietary studies. The influence of dietary modification on the flora will be assessed on the basis of changes in numbers and types of bacteria and their metabolic activity, drawing on data from human and animal studies. The effects of manipulation of the quantity and quality of protein, fat, and indigestible residues (fiber) of the diet will be described together with their possible implications for toxicity of ingested compounds.

Amino Acids↗
PubMed1984

Exposure to low concentrations of mutagens alters the mutagenic and lethal effects of 4-nitroquinoline-N-oxide and mitomycin C in Escherichia coli.

Mitomycin C and 4-nitroquinoline-N-oxide are two mutagens which can induce the SOS DNA repair system in Escherichia coli. Growth of E. coli B/r strain WP2, or its uvrA- derivative, in very low concentrations of either mutagen led to the increased sensitization to the lethal and/or mutagenic effects of a subsequent challenge with the same mutagen. These phenomena were not observed in either the recA- or lexA- derivatives of the parent strain. Induction of the adaptive response repair pathway by prior cultivation in low concentrations of N-methyl-N'-nitro-N-nitrosoguanidine reduced both the mutagenic and lethal effects of a subsequent challenge with mitomycin C but not 4-nitroquinoline-N-oxide.

4-Nitroquinoline-1-oxide↗
PubMed1984

Exposure of E. coli to nitrosocimetidine induces the adaptive response to alkylating agents.

The cytotoxic and mutagenic properties of nitrosocimetidine (NC), together with its ability to induce the adaptive response DNA-repair pathway were compared with those of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) using Escherichia coli as test organism. MNNG was found to be 250-fold more cytotoxic and 500-fold more mutagenic than NC. Prior cultivation of E. coli in low concentrations of NC protected it against the cytotoxic and/or mutagenic effects of challenge with either NC or MNNG or methyl methanesulphonate (MMS). Induction of the adaptive response by prior cultivation in low concentrations of MNNG reduced the mutagenic and cytotoxic effects of subsequent NC challenge. These results lead us to conclude that although NC is a less potent mutagen than MNNG, the DNA lesions it produces are capable of not only inducing, but also of being repaired by, the adaptive response.

Adaptation, Physiological↗
PubMed1984

Dietary lactose and the metabolic activity of the caecal microfloras of weanling and adult rats.

Weanling or adult (9 wk old) rats were fed diets containing 0, 250 or 500 g lactose/kg for 10 days, after which the activities of six caecal microbial enzymes (azoreductase, beta-glucosidase, beta-glucuronidase, nitrate reductase, nitroreductase and urease) were determined. Adult controls had larger caeca than weanlings, but the numbers of bacteria were not significantly different. Expressed in relation to body weight, caecal microbial enzyme activities were significantly lower in adult controls, with the exceptions of beta-glucuronidase and urease. Lactose caused caecal enlargement; this was greatest in weanling animals, which also showed a decreased concentration of bacteria. Lactose increased total nitrate reductase and urease activities in both age groups, but decreased total azoreductase and nitroreductase activities in weanlings. Enzyme activities per 10(9) bacteria were decreased for azoreductase, beta-glucosidase, beta-glucuronidase and nitroreductase in both age groups, while urease activity increased. Azoreductase and nitroreductase activities were highly correlated but nitrate reductase and urease did not correlate significantly with any other enzyme activity.

Aging↗
PubMed1984

Hydrocolloid food additives and rat caecal microbial enzyme activities.

Agar, carboxymethylcellulose, carrageenan, guar gum, gum acacia, locust-beam gum or pectin (50 g/kg diet), given to weanling rats for 4 wk, increased the weight of the caecal wall and the caecal contents. Feeding carboxymethylcellulose, guar gum or pectin significantly increased, and feeding carrageenan decreased, the total bacterial population of the caecum. Feeding carboxymethylcellulose significantly increased in vitro activity of bacterial azoreductase, beta-glucosidase, beta-glucuronidase, nitrate reductase, nitroreductase and urease. Guar gum, gum acacia and locust-bean gum each increased at least three of these activities. In contrast, feeding carrageenan greatly decreased all microbial enzyme activities, while agar decreased beta-glucosidase, beta-glucuronidase and nitroreductase activities.

Agar↗
PubMed1984

Nitrosoproline formation in control and antibiotic-treated rats given nitrate and proline.

The role of the gastrointestinal microflora in the nitrate-dependent formation of nitrosoproline was assessed in control and antibiotic-treated rats. Urinary nitrosoproline excretion as an index of in vivo nitrosamine formation was shown to be unaffected by bacterial decontamination of the alimentary tract, and proceeded in the absence of detectable nitrate reductase activity in the intestinal contents. These observations suggest that the gut microflora are not required for the formation of nitrosamino acid from nitrate and proline.

Animals↗
PubMed1984

Dietary fat and cecal microbial activity in the rat.

Weanling rats were fed low-fat (1% w/w safflower oil) or high-fat (1% w/w safflower oil plus 35% w/w beef fat or cocoa butter) diets for 30 days, and the activities of five cecal microbial enzymes were determined. When compared with the low-fat diet, beef fat significantly increased total cecal beta-glucuronidase activity, but cocoa butter, with a similar fatty acid composition, did not. Both high-fat diets significantly decreased total cecal azoreductase, beta-glucosidase, and nitrate reductase activities, but neither significantly affected urease activity. When expressed as specific activities (per 10(11) bacteria), cocoa butter decreased azoreductase, and beef fat caused increases of beta-glucuronidase and urease. Beef fat, but not cocoa butter, significantly reduced cecal bacterial numbers when compared to the low-fat diet. Both high-fat diets led to equivalent reductions in the proportion of aerobic bacteria.

Anaerobiosis↗
PubMed1983

A comparison of the activity of five microbial enzymes in cecal content from rats, mice, and hamsters, and response to dietary pectin.

Rats, mice, and hamsters were fed a fiber-free purified diet for 30 days and the activity of a number of cecal microbial enzymes was determined. Expressed per gram cecal content, azoreductase activity was greatest in preparations from the hamster and least from the mouse, and beta-glucosidase and beta-glucuronidase activities were least active from the rat. Nitroreductase was less active and nitrate reductase more active from the hamster in comparison to the other species. When expressed per kilogram body weight, bacterial activities were always greatest from the hamster. When the basal diet was supplemented with pectin (50 g/kg diet), nitrate reductase activity was increased six- to sevenfold per gram cecal content for rats and mice (tenfold when expressed per kilogram body weight), but there was no effect on the nitrate reductase activity of hamster microflora. Pectin also significantly increased beta-glucuronidase activity in rats, but significantly reduced the activities of the other enzymes in at least one of the three species.

Animals↗
PubMed1983

Effect of dietary cellulose on the metabolic activity of the rat caecal microflora.

Alpha-cellulose, added to a purified diet at six levels [0%, 2.5%, 5%, 10%, 20%, and 40% (w/w)] and fed to weanling rats for 3 weeks, had no effect on body weight, but it increased the weight of caecal contents and decreased the numbers of bacteria per total caecal contents. Caecal microbial azoreductase, nitroreductase, beta-glucosidase and nitrate reductase activities per total caecal contents were also significantly decreased by 10% dietary cellulose and above, yet beta-glucuronidase activity was only affected significantly by 40% dietary cellulose. Azoreductase and nitroreductase activities were highly correlated with one another and showed a similar response to cellulose.

Animals↗