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Biomedical subjects

I Rowland

Publications and source records attributed to I Rowland.

17 recordsLinked to original sources
PubMed2000

Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells.

Polyphenolic compounds, including isoflavonoids and lignans, have been suggested to be chemopreventive on account of antioxidative properties. In this context it is of importance to have knowledge of their ability to reduce oxidative stress within target cells of tumorigenesis. Therefore, we investigated isoflavonoids and lignans for modulation of oxidative genetic damage in mammalian cells. H(2)O(2)-induced damage as well as endogenous DNA strand breaks and oxidized bases were determined after 30 min incubation of human colon cells with polyphenols using various modifications of the microgel electrophoresis assay (Comet assay). Enterolactone, a mammalian metabolite of plant lignans, was additionally investigated for modulation of intracellular oxidative stress in NIH 3T3 cells using laser scanning microscopy. In vivo effects of rye crispbread (a source of lignans) were investigated in 12 human volunteers by determining genetic damage in lymphocytes and antioxidant activity in plasma (FRAP assay). Genistein induced DNA breaks in the human tumour cell line HT29 clone 19A (12.5-100 microM). The polyphenols (100 microM) did not reduce damage induced by 150 microM H(2)O(2), indicating that they lacked antioxidative potential. At this concentration enterolactone also had no effect on intracellular oxidative stress induced by 31.25 and 125 microM H(2)O(2). In contrast, enterolactone, dihydrogenistein and formononetin reduced endogenous oxidative DNA damage at 100 microM. Daily ingestion of nine slices (76.5 g/day) of rye crispbread per day (containing 41.8 and 33.0 microg/100 g dry weight secoisolariciresinol and matairesinol, respectively) for 2 weeks did not significantly reduce genetic damage in blood lymphocytes, nor was there a modulation of plasma antioxidant capacity. The moderate effects of high concentrations of the tested compounds on endogenous oxidative DNA damage and failure to prevent H(2)O(2)- induced damage are indicative of only marginal protective potential by antioxidant mechanisms. The genotoxic effects of genistein deserve further investigation.

3T3 Cells↗
PubMed1999

The carbohydrate crystalean and colonic microflora modulate expression of glutathione S-transferase subunits in colon of rats.

BACKGROUND: Glutathione S-transferases (GSTs)* are an important class of phase II, predominantly detoxifying, enzymes. The supergene family is composed of several isoenzymes, hetero- and homodimers, with tissue specific distribution and levels of expression. The hypothesis is that a higher expression of individual proteins within a specific tissue may be associated with a decreased burden of exposure to reactive carcinogens and ultimately with a decreased cancer risk in this tissue. AIMS OF THE STUDY: Since nutrition is expected to contribute to the gene expression, it was the aim of this study to investigate the impact of dietary factors, especially resistant starch, and of the gut microflora, which may be influenced by diet, on the GSTs in colon cells of rats. METHODS: For this, a technique using high pressure liquid chromatography was established with which for the first time GST isoenzymes were analysed in colon cells and compared to the levels of the corresponding proteins in the liver of the same rat. RESULTS: It was found that colon cells contain mainly GST pi and low amounts of mu but not GST alpha. In contrast, the predominant form of GSTs in the liver was alpha, then mu and hardly and pi Altogether, liver cells had approximately tenfold more total GSTs than colon cells. The feeding of "Crystalean", a retrograded, high amylose starch which alters the fermentation profile and the composition of the microflora, led to higher levels of GST pi in the colon. Furthermore, the comparison of GSTs in colon cells of germ-free rats revealed they were much lower than those observed in rats with conventional microflora. CONCLUSIONS: These findings clearly demonstrate that the gut bacteria, or their metabolic products, enhance GST expression. The studies support the hypothesis that nutrition--by affecting the gut flora--may induce this potentially protective and important class of phase II enzymes in important tumor target cells.

Amylose↗
PubMed1999

Optimal nutrition: fibre and phytochemicals.

There is currently intense research interest in secondary plant metabolites because of their potential preventative effects on the chronic diseases of Western societies, especially cardiovascular disease and cancer. To date most of the research has focused on the identification of plant-derived substances and their potential protective effects against specific chronic diseases. The important issue of determining the optimal intake of those substances, such that the beneficial effects are maximized without manifestation of adverse effects, has yet to be addressed in most cases. Furthermore, there are no specific functional markers that can be used to assess optimal intake, although it may be possible to use biomarkers such as serum cholesterol if the rest of the diet is strictly controlled. The present review discusses a wide range of substances associated with plants, including dietary fibre, resistant starch, oligosaccharides, phyto-oestrogens, phytosterols, flavonoids, terpenes and isothiocyanates, and attempts where possible to indicate optimal intakes and to suggest functional markers.

Biomarkers↗
PubMed1998

Functional food science and gastrointestinal physiology and function.

The gut is an obvious target for the development of functional foods, acting as it does as the interface between diet and the metabolic events which sustain life. The key processes in digestive physiology which can be regulated by modifying diet are satiety, the rate and extent of macronutrient breakdown and absorption from the small bowel, sterol metabolism, the colonic microflora, fermentation, mucosal function and bowel habit, and the gut immune system. The intestinal microflora is the main focus of many current functional foods. Probiotics are foods which contain live bacteria which are beneficial to health whilst prebiotics, such as certain non-digestible oligosaccharides which selectively stimulate the growth of bifidobacteria in the colon, are already on the market. Their claimed benefits are to alleviate lactose maldigestion, increase resistance to invasion by pathogenic species of bacteria in the gut, stimulate the immune system and possibly protect against cancer. There are very few reports of well-designed human intervention studies with prebiotics as yet. Certain probiotic species have been shown to shorten the duration of rotavirus diarrhoea in children but much more work is needed on the mechanism of immunomodulation and of competitive exclusion and microflora modification. The development of functional foods for the gut is in its infancy and will be successful only if more fundamental research is done on digestive physiology, the gut microflora, immune system and mucosal function.

Bacteria↗
PubMed1996

Lactobacillus- and bifidobacterium-mediated antigenotoxicity in the colon of rats.

Lactic acid bacteria (LAB) are proposed to have several beneficial effects, including the inactivation of carcinogens. We have studied the potential of Lactobacillus acidophilus (from a commercially available yogurt), Lactobacillus gasseri (P79), Lactobacillus confusus (DSM20196), Streptococcus thermophilus (NCIM 50083), Bifidobacterium breve and Bifidobacterium longum (from human infant stool) to prevent the induction of DNA damage by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 7.5 mg/kg body wt) in colon cells of the rat. Using the new technique of single cell microgel electrophoresis, all investigated strains were antigenotoxic toward MNNG after a single dose of 10(10) viable cells/kg body wt p.o. eight hours before the carcinogen. One-half and one-tenth of this initial dose resulted in a loss of protective activity. High doses of heat-treated L. acidophilus strains were also not antigenotoxic. One mechanism of the preventive effect could be that bacterial metabolites or components are responsible. Accordingly, selected examples were investigated in vitro in colon cells of the rat. Metabolically active L. acidophilus cells, as well as an acetone extract of the culture, prevented MNNG-induced DNA damage. Different cell fractions from L. acidophilus (cytoplasm, cell wall skeleton, cell wall) were devoid of antigenotoxic activity, whereas the peptidoglycan fraction and whole freeze-dried cells were antigenotoxic. As a second carcinogen, 1,2-dimethylhydrazine (DMH) was used. A dose- and time-response study was first performed to assess the effects of DMH in several segments of the gastrointestinal (GI) tract. Exposure for 16 hours to 15 or 25 mg DMH/kg body wt p.o. induced DNA damage in cells of the distal colon of rats, whereas no cytotoxicity was seen. Pretreatment orally with LAB on four consecutive mornings before DMH gavage (8 hours after the last LAB application) revealed that L. acidophilus, L. confusus, L. gasseri, B. longum, and B. breve inhibited the genotoxic effect of DMH. One of four S. thermophilus and one of three Lactobacillus delbrueckeii ssp. bulgaricus strains were also protective. Heat-treated L. acidophilus did not inhibit DMH-induced genotoxicity. A few aliquots of the colon cells were processed immunohistochemically for the presence of the "proliferation cell nuclear antigen" (PCNA). DMH treatment did not increase PCNA, nor was there any modulation by LAB. The effect of L. acidophilus on foreign compound-metabolizing enzymes (Phase I and Phase II) in liver and colon cells of rats revealed only one parameter to be modulated, namely, a two- to three-fold increase in the levels of NADPH-cytochrome P-450 reductase. The meaning of this finding, in terms of possible chemoprevention by LAB, remains unclear. In conclusion, our studies show that most, but not all, LAB tested could strongly inhibit genotoxicity in the GI tract of the rat and that viable LAB organisms are required for the protective effect in vivo. The comet assay technique is a powerful tool to elucidate such in vivo antigenotoxic activities in tumor target tissues.

1,2-Dimethylhydrazine↗
PubMed1995

Quality assessment in in vivo NMR spectroscopy: III. Clinical test objects: design, construction, and solutions.

Based on the requirements of test protocols developed to evaluate clinical MRS single slice and volume localisation sequences, two clinical test objects, STO1 and STO2 have been developed. The properties of a range of potential construction materials have been assessed, demonstrating that the water/Perspex interface produced minimum susceptibility effects. The design of the objects has been evaluated in trials on different magnetic resonance instruments, with size and loading being adjusted to allow use on currently available equipment. Appropriate test solutions for 31P and 1H measurements have been developed and their properties evaluated.

Magnetic Resonance Spectroscopy↗
PubMed1981

Simulation of the rat intestinal ecosystem using a two-stage continuous culture system.

To investigate the ecological mechanisms governing the community structure of the gut microbial ecosystem, we have attempted to simulate the rat gut ecosystem in vitro using a two-stage continuous culture. Extensive sampling of the rat hindgut has established a set of criteria with which the in vitro system may be compared. This paper discusses one of the criteria, the community composition and structure in vivo and in vitro. The experiments indicated that a gut microbial ecosystem could be satisfactorily mimicked in vitro. This was achieved using a two-stage continuous culture employing differential selection of species between the two stages on the basis of pH differences combined with cell recycling between stages.

Animals↗
PubMed1975

Specificity of the Escherichia coli proline transport system.

The presence of both the carbonyl portion of the carboxyl group at position 2 of the pyrrolidine ring and a secondary amine was essential for uptake of a compound by the proline permease of Escherichia coli. The permease possessed a high affinity for azetidine-2-carboxylic acid and for compounds with ring structures smaller than the pyrrolidine ring. Pipecolic acid, the higher homologue of proline, and its derivatives were not transported. Cis- and trans-3,4-methano-prolines, also six-membered ring structures, behaved anomolously in that they possessed a high affinity for the permease. The difference between the methano-prolines and other six-membered ring structures probably resides in the fact that the former exist in the "boat" configuration whereas the latter possess the "chair" configuration. In general, substituted prolines in the cis configuration displayed a higher affinity for the permease than did corresponding trans isomers, though the affinity for substituted prolines was influenced by the position, size, and polar or nonpolar nature of the substituent group. At O C many analogues with affinity for proline permease exchanged with intracellular proline, but some analogues, notably trans-3-methyl- and trans-4-methyl-L-prolines, though possessing high affinity for the permease, showed an almost complete inability to exchange with intracellular proline.

Binding Sites↗
PubMedDate not supplied

Biosynthesis of methylmercury compounds by the intestinal flora of the rat.

The contents of the rat cecum and, to a lesser extent, those of the small intestine, synthesized methylmercury from mercuric chloride labeled with Hg 203 in vitro under aerobic or anaerobic conditions. The rate of formation was approximately 18 ng/g cecal contents/20 hr. The synthesis of methylmercury was inhibited by antibiotics and by filtration of the cecal contents through membrane filters, indicating that the bacterial flora of the gut participates in the reaction. Pure cultures of bacteria, isolated from the intestinal tract of the rat, could methylate mercuric chloride. It was estimated that the total amount of methylmercury synthesized from ingested inorganic mercury in man in approximately 400 ng/day.

Anaerobiosis↗