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Biomedical subjects

I R Rowland

Publications and source records attributed to I R Rowland.

At least 73 records · Page 4Linked to original sources
PubMed1988

Influence of starches of low digestibility on the rat caecal microflora.

1. Male Sprague-Dawley rats were fed on either a purified, fibre-free diet or a diet in which half the maize starch was replaced with uncooked amylomaize or potato starch (equivalent to 100 or 200 g amylase-resistant starch (ARS)/kg diet respectively). Changes in short-chain fatty acids (SCFA), pH, ammonia and a number of bacterial variables in caecal contents were then assessed. 2. Both ARS supplements decreased caecal content pH by approximately 1-2 units, with an associated reduction in ammonia concentration. Potato starch significantly decreased the concentration of SCFA in the hindgut, while amylomaize supplementation increased propionic and butyric acids but decreased the occurrence of minor, branched-chain fatty acids. 3. Caecal bacterial biotransformation activities (beta-glucosidase (EC 3.2.1.21), beta-glucuronidase (EC 3.2.1.31), reduction of p-nitrobenzoic acid, apparent ammonia formation) were consistently decreased by both ARS sources. 4. The results demonstrate that amylase-resistant carbohydrate altered toxicologically important functions in the large-intestinal flora of the rat.

Ammonia↗
PubMed1988

Caffeine inhibits hepatic-microsomal activation of some dietary genotoxins.

Hepatic microsomal fractions (microsomes) were prepared from female BALB/c mice. The potential of caffeine to modify the ability of microsomes to convert the heterocyclic aromatic amines MeIQ, Trp-P-2 and MeIQx, to bacterial mutagens (indicator: Salmonella typhimurium TA98) was investigated. Caffeine inhibited mutagenicity and did so by inhibiting microsomal metabolism of the three compounds, rather than by altering uptake of the active mutagens and/or interacting with the DNA repair processes in the bacterial cell. Notional Ki values determined for the three heterocyclic amines were similar, suggesting that caffeine inhibits at a stage common to the metabolism of all three compounds.

Animals↗
PubMed1988

Interactions of the gut microflora and the host in toxicology.

Food components and ingested chemicals may be metabolized in the gut, not only by digestive and intestinal mucosal enzymes, but also by the resident bacteria, which are found in greatest numbers in the large intestine. The gut microflora is a large (about 10(11) organisms per g colon contents) and diverse (over 400 species) population of organisms and possesses a correspondingly diverse range of metabolic activities, including reductions, hydrolyses and degradations. In many cases, these reactions both complement and antagonize those of the liver, which are mainly oxidative and synthetic. The metabolism, by the gut flora, of chemicals ingested in food or secreted in bile can have numerous toxicological sequelae, including activation to more toxic, mutagenic or carcinogenic derivatives, detoxication and enterohepatic circulation. These toxicological consequences may be modified by changes in the flora due to diet, drugs and interindividual differences. Examples presented of the interaction between the gut flora and its host are the influence of intestinal bacteria on hepatic tumor incidence in mice, the effect of bacterial hydrolysis of rutin on the activity of hepatic enzymes which activate dietary carcinogens, and the role of the gut flora in demethylation and detoxication of methylmercury.

Animals↗
PubMed1988

Factors affecting metabolic activity of the intestinal microflora.

1. The metabolic activity of the gastrointestinal microflora can be modified by numerous factors derived from the host, the host's environment, and the flora itself. 2. Marked differences exist in microbial composition and metabolism of the gut floras of different species of animal, and in the degree of colonization of the various regions of the gut. 3. The microbial flora changes with age, particularly in early infancy, and developmental changes in in vivo metabolism attributable to the gut flora have been noted for methylmercury. 4. Gastrointestinal disease can have a profound effect on microbial colonization and metabolism in the upper regions of the human gut. In particular, hypochlorhydria can lead to elevation in bacterial numbers, and nitrite and nitrosamine concentrations in gastric juice. 5. Environmental factors such as drugs (particularly antibiotics), diet, and xenobiotics can modify microbial metabolism and toxicity of foreign compounds. In some cases exposure to xenobiotics (e.g., cyclamate, rutin) results in metabolic adaptation and increased biotransformation of the foreign compound. 6. By their fermentation of dietary residues and endogenous carbohydrates, the gut bacteria produce acids which can lower lumenal pH and, in turn, modify bacterial enzyme activities. However, the changes in activity appear to be enzyme specific, some increasing with pH and others being inversely related to pH of incubation.

Humans↗
PubMed1987

Counteraction of the genotoxicity of some cooked-food mutagens by biogenic amines.

The biogenic amines tryptamine, 5-hydroxytryptamine, tyramine and histamine were assessed for their abilities to modify the genotoxicity of the cooked-food mutagens IQ, MeIQ, MeIQx, Trp-P-1 and Trp-P-2. These measurements were made using a bacterial mutation assay with hepatic fractions from either SWR mice or DSN Syrian hamsters as the activating system and Salmonella typhimurium TA98 as the indicator organism. Although histamine had very little effect on the genotoxicity of these mutagens, the other amines reduced genotoxicity, with tryptamine and 5-hydroxytryptamine exerting the greatest effect. Generally the amines exhibited greater potency when S-9 fractions from mice rather than from hamsters were used.

Animals↗
PubMed1987

The hepatic conversion of some heterocyclic amines to bacterial mutagens is modified by dietary fat and cholesterol.

Groups of Sprague-Dawley rats were fed on diets containing increasing amounts of beef dripping, but having a constant cholesterol content. One group of rats was fed on a diet containing no dripping and no added cholesterol (control). We have studied the ability of individual hepatic S9 preparations to activate the cooked food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX) to bacterial mutagens using Salmonella typhimurium TA98 as indicator. Hepatic preparations from animals fed on a high cholesterol, low-fat diet were less effective in activating the mutagens than preparations from rats fed on the control diet. It was also observed that the capacity of hepatic preparations to activate these mutagens increased as the amount of dripping in the diet increased. These results suggest that it is the triglyceride rather than the cholesterol content of beef dripping which promotes increased mutagen activation capacity in the liver.

Animals↗
PubMed1987

The use of rats associated with a human faecal flora as a model for studying the effects of diet on the human gut microflora.

The activities of four bacterial biotransformation enzymes (beta-glucosidase, beta-glucuronidase, nitrate reductase and nitroreductase) were measured in the caecal contents of conventional flora rats or germ-free rats contaminated with a mixed, human faecal flora and compared with activities present in a fresh human stool preparation. Both the conventional flora rats and the rats inoculated with a human flora exhibited an enzyme profile generally similar to that of human faeces, although the conventional rat flora exhibited negligible nitrate reductase activity. The enzyme profile remained essentially unaltered in both human flora preparations following supplementation of the diet with pectin, whereas the conventional rat flora responded to this plant cell wall carbohydrate with a significant increase in nitrate reductase activity. The results demonstrate that enzymic activities of the human faecal microflora can be simulated in rats associated with a mixed population of human intestinal bacteria.

Adult↗
PubMed1987

Dietary modification of intestinal bacterial enzyme activities--potential formation of toxic agents in the gut.

The bacterial population colonising the large intestine is able to metabolise a variety of ingested or endogenously produced substances to products, some of which possess toxic, mutagenic or carcinogenic properties. Dietary components, resistant to digestion and absorption in the upper alimentary tract, may influence these reactions by altering the environment of the gut or through the provision of nutrients to the flora. Evidence for the involvement of bacterial enzymes in the formation of toxic products in vivo has come largely from animal studies, particularly where fermentable plant cell-wall components are present in the diet. The role of diet in the modification of toxicologically important bacterial biotransformation processes will be discussed. Preliminary data will also be presented from a study demonstrating changes in the enzymic activity of the human faecal flora induced by pectin and bran. The significance of these changes to the disposition of chemicals in the gut will be discussed.

Ammonia↗
PubMed1987

High levels of dietary fat: alteration of hepatic promutagen activation in the rat.

Male Ola:Sprague-Dawley rats were fed diets containing either low or high levels of fats. After being fed these diets for 4 weeks, the rats were killed and individual hepatic postmitochondrial (S9) fractions were prepared. The ability of these fractions to convert the heterocyclic aromatic amines (HAAs)--2-amino-3-methylimidazo[4,5-f]quinoline; 2-amino-3,4-dimethylimidazo[4,5-f] quinoline; and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (compounds produced during the cooking of proteinaceous food)--to bacterial mutagens was studied, with the use of Salmonella typhimurium TA98 as indicator. Fractions from rats fed high-fat diets exhibited a greater ability to activate the HAAs than did those from rats fed the low-fat diet. The magnitude of the increase was dependent on the type of fat used.

Animals↗
PubMed1986

The effect of various dietary fibres on tissue concentration and chemical form of mercury after methylmercury exposure in mice.

The whole-body retention of mercury after exposure of BALB/c mice to methylmercury was measured in animals fed fibre-free, 5% pectin, 5% cellulose or 5, 15 or 30% wheat bran diets. The rate of elimination of mercury was dependent on the diet fed, with dietary bran increasing the rate of elimination. The incorporation of 15 or 30% bran in the diet of the mice decreased the total mercury concentration in the brain, blood and small intestine, although the effects were significant only in those animals on 30% bran diet. The fibres had little effect on mercury levels in other tissues. The proportion of mercury found in the mercuric form was significantly greater in liver, kidneys and gut of mice fed bran. The results suggest that dietary bran may reduce the levels of mercury in the brain after methylmercury exposure and may therefore reduce the neurotoxic effects of the organomercurial. We suggest that wheat bran exerts its effects on mercury retention and brain level via a modification of the metabolic activity of the gut microflora.

Animals↗
PubMed1986

Effects of plant-derived flavonoids and polyphenolic acids on the activity of mutagens from cooked food.

The ability of 3 plant flavonoids (morin, myricetin and quercetin) and 4 polyphenolic acids (caffeic acid, chlorogenic acid, ellagic acid and ferulic acid) to inhibit the genotoxic effects of a number of cooked-food mutagens (IQ, MeIQ, MeIQx, Trp-P-1 and Trp-P-2), was investigated in a bacterial mutation assay using Salmonella typhimurium TA98 as indicator and hepatic S9 mixes from either SWR mice or Syrian hamsters as metabolic activating systems. Although the polyphenolic acids failed to have an effect, the flavonoids generally inhibited IQ, MeIQ, MeIQx and Trp-P-1 induced mutagenesis in a dose-dependent manner, irrespective of the source of S9. This was not the case with Trp-P-2 where the flavonoids were only observed to inhibit when SWR mouse S9 but not Syrian hamster S9 was used. Of the 3 compounds, myricetin and quercetin were superior to morin in their inhibitory capacity.

Animals↗
PubMed1986

Metabolic conversion of IQ and MeIQ to bacterial mutagens.

The metabolic conversion of 2-amino-3-methyl- and 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (IQ and MeIQ respectively) to bacterial mutagens was studied using a bacterial mutation assay. Studies were performed using S9 fractions derived from either corn oil (uninduced) or Aroclor-1254-treated Sprague-Dawley rats. Aroclor 1254 treatment lowered the S9 protein concentration required for optimum levels of mutagenesis, enhanced the numbers of mutants observed and altered the effects of metabolic inhibitors and cofactors added to the assay. Studies with uninduced preparations revealed that IQ and MeIQ exhibited similar responses to the effects of metabolic inhibitors and cofactors involved in detoxication reactions. Both IQ and MeIQ activation appeared to be inhibited by the biogenic amines tryptamine and tyramine and inactivated by conjugation with either acetyl coenzyme A or glutathione.

Acetyl Coenzyme A↗
PubMed1986

Induction of unscheduled DNA synthesis in rat and hamster hepatocytes by cooked food mutagens.

The genotoxicity of the cooked-food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was studied by monitoring the induction of DNA repair (unscheduled DNA synthesis; UDS) in primary cultures of rodent hepatocytes. The hepatocytes were derived from male Sprague-Dawley rats or Syrian hamsters by collagenase perfusion and the cells were cultured for 4 hr before being exposed to various concentrations of the mutagens. DNA repair was determined by measuring incorporation of [3H]thymidine into extracted DNA over 17 hr using beta-scintillation counting. Dose-related increases in UDS were clearly seen in hamster hepatocytes treated with MeIQ, IQ and the positive control 2-acetylaminofluorene (AAF), and a weak response was induced by MeIQx and Trp-P-1. In the rat hepatocytes only MeIQ and AAF gave clear positive responses. Furthermore it was noted that all the mutagens displayed a more pronounced UDS response in hamster hepatocytes than in rat cells. Studies of the activation of MeIQ by hepatocytes to a bacterial mutagen suggest that this difference is probably a consequence of the greater capacity of hamster cells to activate the mutagens to genotoxic metabolites.

Animals↗
PubMed1986

Effect of mixtures of dietary fibres on the enzyme activity of the rat caecal microflora.

The enzyme activity of the caecal microflora from weanling rats was determined after feeding 1 of 3 basal diets (purified fibre-free; purified plus cellulose; and stock), with or without additional dietary fibre (pectin, i-carrageenan or carboxymethylcellulose 5% w/w). The wet weight of caecal contents and total bacterial numbers were similar for the purified fibre-free and purified plus cellulose diets, yet were significantly higher in animals fed the stock diet. Pectin supplementation of the basal diets had no effect of caecal bacterial numbers, but significantly increased total nitrate reductase activity per caecum except when added to stock diet. Carrageenan decreased caecal bacterial numbers and most enzyme activities with both purified diets, and to a lesser extent with the stock diet. Carboxymethylcellulose increased bacterial numbers and enzyme activities, particularly beta-glucosidase and nitrate reductase when added to the purified diet but not when added to either the purified diet plus cellulose or the stock diet. The results demonstrate that the effects of dietary fibre components on the rat caecal microflora are dependent upon the initial fibre content of the diet base.

Animals↗
PubMed1986

Influence of wheat bran on some reductive and hydrolytic activities of the rat cecal flora.

For 30 days, male weanling rats were fed a semipurified, fiber-free diet or a diet that contained 5, 15, or 30% (wt/wt) wheat bran. The activities of four cecal microbial enzymes were determined. Wheat bran significantly increased the wet weight content of the cecum and total bacterial count per cecum at the intermediate- and high-treatment levels, but it had no effect on bacterial concentration per gram wet weight of cecal contents. Total beta-glucosidase and beta-glucuronidase activities per cecum were generally increased. Wheat bran decreased total nitrate reductase activity, but there was no change in total nitroreductase activity. Wheat bran significantly decreased enzyme activities for nitro-and nitrate reduction per gram of cecal contents but increased beta-glucosidase activity. The activities of the enzymes per 10(11) bacteria followed a similar pattern to that noted per gram of cecal contents. Such fiber-dependent changes in enzyme activity may alter the steady-state concentration of toxic and genotoxic chemicals in the lumen of the hindgut.

Animals↗