PubMed Health⌕ Search

Biomedical subjects

M B Roberfroid

Publications and source records attributed to M B Roberfroid.

At least 37 records · Page 2Linked to original sources
PubMed1996

Functional effects of food components and the gastrointestinal system: chicory fructooligosaccharides.

Functional food science, as recently proposed by ILSI Europe, opens new perspectives in nutrition and food sciences. The systematic investigation of the interactions between food components or food ingredients and genomic, biochemical, cellular, or physiological functions is a unique way to improve both our knowledge and the role of nutrition in maintaining good health and in preventing disease. However, such basic knowledge is insufficient to justify claims, unless it is confirmed through relevant nutrition studies aimed at demonstrating the same effect and its positive consequences in humans. In the first stage, this demonstration will in most cases justify functional (physiological) claims (e.g., bifidogenic effect for fructooligosaccharides, bulking effect for nondigestible carbohydrates, protection against oxidative stress for antioxidants) with no reference to any health benefit. A true health claim will require, in most cases, additional studies involving large populations and long-term trials. It is anticipated that the better we understand the mechanism of interactions between food components and specific biological functions, the more we will be able to demonstrate functional effects, and the easier it will be to accumulate convincing evidence in favor of health promotion or disease prevention. Because of both its direct contact with eaten foods and the diversity of its functions, the GI system is a potential target for many functional effects. Until now, only a limited number of these effects have been investigated so as to justify functional claims. Improvement of glucose absorption (leading to physiological glycemia and insulinemia), modulation of GI transit time, fecal bulking, acidification of colonic content, and control of cholesterol bioavailability are all recognized effects of dietary fiber. Balanced colonic microflora and immunostimulation are attributed to the consumption of probiotics. Prebiotics selectively modify the colonic microbiota and modulate hepatic lipogenesis. According to the ILSI Europe strategy for the development of functional foods, all these effects are of interest. Their support by sound scientific arguments will be a necessary condition for their implementation in food science and nutrition for the benefit of human health.

Cichorium intybus↗
PubMed1995

Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics.

Because the human gut microbiota can play a major role in host health, there is currently some interest in the manipulation of the composition of the gut flora towards a potentially more remedial community. Attempts have been made to increase bacterial groups such as Bifidobacterium and Lactobacillus that are perceived as exerting health-promoting properties. Probiotics, defined as microbial food supplements that beneficially affect the host by improving its intestinal microbial balance, have been used to change the composition of colonic microbiota. However, such changes may be transient, and the implantation of exogenous bacteria therefore becomes limited. In contrast, prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota. Nondigestible oligosaccharides in general, and fructooligosaccharides in particular, are prebiotics. They have been shown to stimulate the growth of endogenous bifidobacteria, which, after a short feeding period, become predominant in human feces. Moreover, these prebiotics modulate lipid metabolism, most likely via fermentation products. By combining the rationale of pro- and prebiotics, the concept of synbiotics is proposed to characterize some colonic foods with interesting nutritional properties that make these compounds candidates for classification as health-enhancing functional food ingredients.

Bacteria↗
PubMed1995

Colonic microflora: nutrition and health. Summary and conclusions of an International Life Sciences Institute (ILSI) [Europe] workshop held in Barcelona, Spain.

The colonic microflora is an organism that performs a variety of unique activities. It is more important to evaluate these activities than to analyze bacterial composition in terms of genera, species, or strains. Unless the bacteria translocate, it is the activities of the colonic microflora that affect colonic and systemic physiology and not the bacteria themselves.

Colon↗
PubMed1994

Changes in bile acids metabolism during rat hepatocarcinogenesis: causative or unrelated?

In the present paper, we have aimed at studying the variations in the metabolism of bile acids occurring during an hepatocarcinogenic process induced in male Wistar Rats by the biphasic protocol of Solt and Farber. Bile acids concentrations was measured in the liver. The most significant changes have been observed 5 weeks after the beginning of the treatment, it means one week after the selection treatment consisting in 2-acetylaminofluorene administration: the increase in cholic acid, and of its intestinal metabolite, deoxycholic acid, and of alpha- and beta- muricholic acids, are likely to be a consequence of an acute effect of 2-acetylaminofluorene. To test for the putative implication of liver bile acids modifications in the selection effect of 2-acetylaminofluorene, diethyl-nitrosamine-pretreated rats were fed a diet containing 1% lithocholic acid, a treatment that induces essentially the same qualitative changes in liver bile acids, as 2-acetylaminofluorene does: no selection effect of lithocholic acid could be demonstrated. These results suggest that changes in bile acid metabolism occurring early in hepatocarcinogenesis are more likely to be secondary than causative events. The same conclusion comes from the results obtained later on in the process, where there is only a high increase in liver cholic acid and deoxycholic acid concentrations.

2-Acetylaminofluorene↗
PubMed1992

Synergism between aflatoxin B1 and oxytetracycline on fatty acid esterification in isolated rat hepatocytes.

The individual and combined effects of aflatoxin B1 (AFB1) and oxytetracycline (OXT) on the synthesis and secretion of triacylglycerols in isolated rat hepatocytes maintained in suspension during 2.5 h were studied. Secretion of triacylglycerols was inhibited by both drugs when administered separately. This inhibition was accompanied by a concomitant elevation of intracellular triacylglycerols only at the highest AFB1 dose tested. Total synthesis of triacylglycerols was not inhibited by AFB1 or by OXT. When the two drugs were simultaneously added to the incubation medium, the AFB1-induced accumulation of intracellular triacylglycerols was no longer observed; the inhibition of secretion was nevertheless identical to that observed with AFB1 alone. Finally, total esterification of palmitate was inhibited by 20% compared to the AFB1-treated cells. These data suggest that OXT inhibits lipid accumulation induced by AFB1 but that this effect is due to an inhibition of total synthesis of triacylglycerols. The mechanism of AFB1's effect and of the interaction between both molecules is discussed.

Aflatoxin B1↗
PubMed1992

Comparative hepatotoxicity of cholic acid, deoxycholic acid and lithocholic acid in the rat: in vivo and in vitro studies.

Until now, the cytotoxicity of the bile acids was mostly seen as being inversely associated with their degree of lipophilicity. The present study aimed at comparing the hepatotoxicity of cholic acid (CA), deoxycholic acid (DCA) and lithocholic acid (LCA), which are respectively, tri-, di- and monohydroxylated bile acids. For in vivo studies, the bile acids have been given at the dose of 0.5% or 1% in the diet of male Wistar rats for 2 weeks. The histological analysis of the liver, and the measurement of serum parameters of cytotoxicity and cholestasis (aminotransferases activity, bilirubin and total bile acids concentration), indicate that, among the bile acids tested, DCA is the most hepatotoxic, at both doses, while CA is the least hepatotoxic and cholestatic compound. Moreover, DCA is the only bile acid which, when given at the dose of 0.5%, induces lipid peroxidation in the liver, as evidenced by the measurement of thiobarbituric reactive substances in liver homogenates. The analysis of bile acids in liver homogenates by gas liquid chromatography revealed that feeding the animals with DCA results in its hepatic accumulation. Feeding rats with LCA or CA only slightly modifies the proportion of tri-, di- and monohydroxylated bile acids in the liver, as compared to controls. An in vitro experiment aimed at studying the hepatocellular lysis induced in vitro by the three bile acids by measuring the release of lactate dehydrogenase in the incubation medium of surviving hepatocytes in suspension. At a concentration of 1 mM, only DCA induces a significant cellular lysis, while at this concentration the lytic effects of CA and LCA are progressive and time-dependent. From this study, we gather that the hepatotoxicity of bile acids does not necessarily depend on their degree of hydroxylation. Our results are in accordance with some studies in rat hepatocarcinogenesis, showing a predominant initiating and promoting effects of DCA, as compared to LCA.

Administration, Oral↗
PubMed1990

Interaction between aflatoxin B1 and oxytetracycline in isolated rat hepatocytes.

Isolated rat hepatocytes were used as an in vitro model to investigate a possible interaction between oxytetracycline (OXT) and aflatoxin B1 (AFB1). LDH leakage, RNA and protein synthesis and glycogen accumulation were measured in the presence of both drugs, either separately or in combination. The evolution of LDH leakage during the incubation was identical in untreated and treated cells. AFB1 inhibited RNA and protein synthesis at a concentration of 10(-7) M and 10(-6) M, respectively, and higher, whereas OXT did not influence RNA synthesis but inhibited protein synthesis at the highest tested concentration, 10(-3) M. As far as glycogen is concerned, rats were injected with glucagon before sacrifice in order to obtain a constant synthesis rate in isolated hepatocytes. AFB1 inhibited the accumulation of glycogen from 10(-6) M upward. This effect was never observed before 90 min of incubation. OXT had no effect on glycogen synthesis. In the presence of both drugs, no interaction was demonstrated as far as RNA and protein synthesis were concerned, but OXT opposed the inhibition induced by AFB1 on glycogen accumulation. If the "in vivo" protection, provided by OXT against AFB1-induced toxicity, is due to a direct interference in the toxic mechanisms of the mycotoxin, these results show that OXT does not influence the AFB1-inhibition of RNA and protein synthesis. The latter are early and sensitive parameters inhibited by AFB1. On the contrary, taking into consideration the results on glycogen accumulation, it seems more interesting to investigate further this metabolism.

Aflatoxin B1↗
PubMed1990

Predictive value of serum alkaline DNase activity variations in treatment of head and neck cancer.

The aim of this study was to evaluate the variation in serum alkaline DNase activity (SADA) as a means of therapeutic monitoring in patients with head and neck cancer. Blood samples from 40 patients were collected before, during, and some weeks up to months after therapy. A decrease in SADA during treatment was usually associated with a primary clinical response, while no decrease indicated non-response to therapy. In patients with complete tumor regression the initial decrease of SADA was usually followed by an increase exceeding the initial level. A similar increase was not observed in patients with tumor progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Variations in serum alkaline DNase activity in rats during growth and treatment of tumors sensitive or resistant to therapy.

Serum alkaline DNase activity (SADA) was investigated in rats receiving s.c. transplants of tumor cells sensitive or resistant to chemotherapy. Serum samples from each animal were collected before transplantation, during the development of tumors and after therapy. Within a few days after transplantation of both tumor lines (sensitive or resistant), SADA levels decreased progressively to 52% of the normal pre-transplantation level (p less than 0.01). This decrease in SADA preceded by 4 to 5 days the appearance of any palpable tumor mass. In all untreated animals as well as in treated rats bearing resistant tumors, SADA remained at a low level until death. In rats bearing tumors sensitive to therapy a progressive increase in SADA was observed after treatment, paralleling tumor regression. When tumor regression was complete, SADA resumed the levels of activity measured prior to transplantation.

Adenocarcinoma↗
PubMed1988

Characteristic variations of serum alkaline DNase activity in relation to response to therapy and tumor prognosis in human lung cancer.

The objective of the present study was to evaluate serum alkaline DNase activity (SADA) variations as a useful means of lung cancer monitoring therapy. SADA was measured in 40 patients with non-small cell and small cell carcinomas. Blood samples were collected before (Time 0), during the treatment and months after therapy. A decrease in SADA during the first treatment indicates a good clinical response, whereas an absence of decrease indicates a non-response to treatment. In patients who respond to therapy, three types of variations of SADA are observed during the clinical course. A progressive regaining of SADA up to a value largely exceeding the level of the initial SADA value (T0) correlates with a complete remission. An incomplete regaining of enzyme activity corresponds to a partial remission, whereas no regaining of SADA precedes a fatal evolution. Such variations in SADA observed in the 40 patients with lung carcinomas support our previously published clinical results, confirming that the variations of SADA could be a reliable marker for the therapeutic monitoring of different human malignancies.

Aged↗
PubMed1985

Oesophageal cancer studies in the Caspian littoral of Iran: some residual results, including opium use as a risk factor.

A study was conducted in northern Iran in areas of very high, high and moderately low incidence of oesophageal cancer. Morphine metabolites in urine as an indicator of opium use, and a variety of nutritional and biochemical measures, including salivary antipyrine half-life, were determined in households with a case of oesophageal cancer and in control households. Results on 1,590 individuals showed that the prevalence of appreciable levels (greater than or equal to 1 microgram/ml) of urinary morphine metabolites was much higher in areas of high and very high incidence of oesophageal cancer than in low-incidence areas, particularly for those under age 50 years in both sexes, where a 6-fold difference was seen. Members of households with a case of oesophageal cancer had a higher prevalence of positive urinary morphine metabolite findings than members of control households from the same village. Salivary anti-pyrine half-life (AP-T1/2), as a measure of hepatic drug metabolizing capacity, was estimated in 120 subjects. No relationship was seen with use of opium, region of residence, case-control status of household, age or sex. Experimental studies have meanwhile identified mutagenic substances with carcinogenic potential in opium pipe scrapings, used widely in the study region, opium pyrolysates and morphine pyrolysates. Our data give additional support to the hypothesis that opium use, in the form of its pyrolysates, is one of the factors involved in the aetiology of oesophageal cancer in the region.

Adolescent↗
PubMed1983

Interrelationships in mice of antipyrine half-life, hepatic monooxygenase activities and liver S9-mediated mutagenicity of aflatoxin B1, benzo[alpha]pyrene 7,8-dihydrodiol, 2-acetylaminofluorene and N-nitrosomorpholine.

To evaluate the predictive value of serum antipyrine half-life AP(T1/2) as an index of hepatic carcinogen metabolism, groups of C57BL/6 and DBA/2 mice were treated with various inducers and inhibitors of cytochrome P-450-dependent monooxygenases (pregnenolone-16 alpha-carbonitrile (PCN), phenobarbital (PB), 5,6-benzoflavone (5,6-BF), 3-methylcholanthrene (MC), disulfiram (DIS), 7,8-BF). Groups of mice were also given ethanol (3% in drinking water) for 12 days. Within each group, mean serum AP-(T1/2) was compared with (i) the in vitro activity of hepatic microsomal benzo[alpha]pyrene (BP) 3-hydroxylase, 2-acetylaminofluorene (AAF)-N-hydroxylase and aldrin monooxygenase, and (ii) the liver S9-mediated mutagenicity of aflatoxin B1 (AFB), trans-7,8-dihydro-7,8-dihydroxybenzo[alpha]pyrene (BP 7,8-diol), 2-acetylaminofluorene and N-nitrosomorpholine (NMOR) in Salmonella typhimurium strains. Serum AP(T1/2) was only correlated negatively with the activity of BP 3-hydroxylase (P less than 0.001) and aldrin monooxygenase (P less than 0.001). No statistically significant correlation was found between serum AP(T1/2) and liver S9-mediated mutagenicity for any of the four carcinogens. On the basis of these results, we conclude that serum AP(T1/2) may not be a reliable index of the capacity of liver to convert carcinogens into reactive intermediates.

2-Acetylaminofluorene↗
PubMed1983

Phenobarbital as a promoter in the initiation/selection process of experimental rat hepatocarcinogenesis.

Supplementary introduction of a phenobarbital (PB) promotion step after the Solt and Farber procedure dramatically increases the number of phenotypically-altered hepatocytes. These hepatocytes occupy approximately 40% of the liver volume after one week of PB treatment. These areas constitute a relatively uniform cellular population with altered histological phenotype and with distinct histochemical markers used by other authors for the detection of premalignancy. This procedure leads to the appearance of numerous hepatocellular carcinomas at approximately the 36 weeks stage. It was suggested that the early hepatocellular alterations after the initiation/selection procedure followed by PB might correspond to the hyperplasia of phenotypically-altered epidermal cells at the conversion step of mouse skin tumor promotion.

2-Acetylaminofluorene↗
PubMed1982

Species differences in the biochemical properties of liver microsomal arylamine and arylamide n-hydroxylases.

Cytochrome P-448 dependent microsomal N-hydroxylases are key enzymes in the metabolic activation of both arylamides and arylamines. Using 2-acetylaminofluorene (2-AAF) and 2-aminofluorene (2-AF) as substrates, the present report compares the biochemical properties of rat, hamster and mouse liver N-hydroxylases. There are marked species differences both in terms of the affinity for the two substrates and in terms of maximum velocity of the enzymes. The rat and hamster liver arylamide N-hydroxylases are induced by pretreatment with 2-AAF which also significantly increases their affinity for the substrate. In mouse liver neither arylamide nor arylamine N-hydroxylases are modified or induced. With 2-AF as substrate, arylamide treatment never enhances N-hydroxylation but it reduces the Km-value of the rat and hamster liver enzymes. Among the effectors tested in vitro, 3-methylcholanthrene (3-MC), 7,8-benzoflavone (BF), benzo[a]pyrene (B[a]P) and miconazole (MN) inhibit hepatic arylamide N-hydroxylase in the submicromolar range. Harman (H) and paraoxon (PX) act in a dose-dependent manner in the micromolar range and metyrapone (MP) is not an inhibitor even at 50-microM concentration. Among the position isomers, 1- and 3-AAF are inhibitors of the N-hydroxylating enzymes whereas 4-AAF is not.

2-Acetylaminofluorene↗
PubMed1982

Biochemical effects of nitrosopyrrolidine on isolated hepatocytes.

The present communication reports the effects of N-nitroso-pyrrolidine (NPYR) on some essential metabolic pathways in isolated hepatocytes. Isolated cells prepared by the collagenase-perfusion technique are incubated for 4 hours in suspension in a Waymouth medium, either in the absence or in the presence of NPYR (20 to 40 mmol/l). Under these conditions, NPYR, even at 40 mmol/l, has no effect on the vital staining of the cells by erythrosin B and does not increase the leakage of LDH, indicating no lethal effect. However, the glycogen synthesis which occurs in control cells is inhibited in presence of NPYR and the intracellular glycogen is even degraded. This effect is accompanied by reactivation of phosphorylase 'a'. NPYR also affects the protein synthesis capacity of the isolated hepatocytes. Incubation in the presence of non-metabolizable labelled amino acids has demonstrated that such an effect could be explained by a specific action of NPYR on the L-transport system for amino acids through the hepatic plasma membrane.

Animals↗
PubMed1980

Metabolic activation of drugs in mutagenicity tests in vitro.

The metabolic pathways of chemical compounds of pharmaceutical interest are reviewed in relation to the role of activation and detoxification in the process of mutagenicity. The properties and subcellular localization of the enzymes involved are given together with the main reactions they catalyze. The role of metabolism in mutagenicity testing in vitro is discussed with special emphasis on the choice of the enzymatic system. Parameters such as species, strain, sex, diet, and induction are considered. The effect of various enzymatic effectors added in vitro is also discussed. It is concluded that the metabolism of drugs is very complex, involving both activation and detoxification processes catalyzed by a large variety of enzymes. Production of mutations in vitro in prokaryotic or eukaryotic cells is the results of a balance between all those pathways. Metabolic activation thus merits special attention.

Animals↗
PubMed1977

Michaelis--Menten kinetic analysis of the hepatic microsomal benzpyrene hydroxylase from control, phenobarbital- and methyl-3-cholanthrene-treated rats.

The sensitive fluorimetric assay for hydroxy-3-benzpyrene (3-OH-BP) described by Dehnen et al., was used to study the effect of microsomal membrane concentration of the benzpyrene hydroxylase activity. Microsomes from phenobarbital (PB) and methyl-3-cholanthrene (3-MC)-treated rats were used in comparison with the microsomal fraction from control animals. At very low protein concentration, benzpyrene hydroxylase follows as Michaelis--Menten type kinetics. When the concentration of microsomal membrane is higher than a minimal value (+/- 6 mug protein/ml) the Km increases with increasing concentration of protein due to competitive inhibition by reversible and non-specific binding of the substrate. The Ki's for such a binding have been calculated. Pretreatment of rats with 3-MC selectively shortens the time linearity, decreases the Ks value, and has no effect on Vmax, while the administration of PB prolongs the time linearity, decreases Vmax and does not modify the Ks. 3-MC and PB specifically act on cytochrome P-450 and do not modify the physico-chemical properties of the microsomal membrane as measured by the non-specific binding of benzpyrene (BP).

Animals↗