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Biomedical subjects

M Roberfroid

Publications and source records attributed to M Roberfroid.

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

Dietary oligofructose modifies the impact of fructose on hepatic triacylglycerol metabolism.

The aim was to investigate if chronic feeding with oligofructose (OFS), a nondigestible fructan that decreases triacylglycerol-very-low-density lipoproteins (TAG-VLDLs) in the serum of rats by reducing hepatic de novo lipogenesis, could counteract the impact of fructose on TAG metabolism. Male Wistar rats fed a standard diet supplemented or not with 10% OFS for 30 days received either tap water or a 10% fructose drinking solution for 48 hours. TAG, phospholipids (PLs), cholesterol, and free fatty acids were assayed both in serum and in liver. Fatty acid de novo synthesis, esterification, and beta-oxidation were assessed in the liver by measuring the activity of key enzymes: fatty acid synthase (FAS), phosphatidate phosphohydrolase (PAP), glycerol-3-phosphate acyltransferase (GPAT), and carnitine palmitoyltransferase-I (CPT-I), respectively. The acute load of fructose increased (1) both liver and serum TAG without affecting other lipids, and (2) de novo fatty acid synthesis and esterification, through induction of FAS and PAP without affecting CPT-I. Long-term feeding with OFS protected rats against liver TAG accumulation induced by fructose. The lower lipogenic capacity of the liver could be the key event in this protection, since even after the fructose load FAS activity remained significantly lower in OFS-fed rats. However, despite its protective effect on the liver, OFS was not able to prevent fructose-induced hypertriglyceridemia, suggesting that OFS feeding could not counteract the fructose-induced defect in TAG-VLDL clearance.

Animals↗
PubMed1996

Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats.

Dietary supplementation with oligofructose (OFS; 100 g/kg), a non-digestible oligomer of beta-D-fructose, decreases serum triacylglycerols in serum and VLDL of rats. In order to investigate the role of hepatic metabolism in the hypolipidaemic effect of OFS, male Wistar rats were fed on a standard diet with or without 100 g Raftilose P95/kg as OFS source for 30 d. OFS feeding (1) significantly decreased triacylglycerol and phospholipid concentrations in both blood and liver, (2) increased the glycerol-3-phosphate liver content but decreased the hepatic activity of glycerol-3-phosphate acyltransferase (EC 2.3.1.15), suggesting a decrease in acylglycerol synthesis, (3) did not affect the blood non-esterified fatty acid concentrations, but (4) reduced by 54% the capacity of isolated hepatocytes to synthesize and secrete triacylglycerols from labelled acetate; the activity of fatty acid synthase, a key lipogenic enzyme was also significantly decreased. These findings suggest that OFS decreases serum triacylglycerols by reducing de novo fatty acid synthesis in the liver; the lower insulin level in the serum of OFS-fed rats could explain, at least partly, the metabolic effect induced by such non-digestible carbohydrates.

Animals↗
PubMed1995

Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats.

The present study was aimed at answering the question why feeding rats an oligofructose (OFS) supplemented diet could cause a significant reduction in plasma lipid levels. Daily administration of a 10% (w/w) OFS-containing diet to normolipidemic male rats resulted in a decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect was observed after one week and lasted for at least 16 wk and was associated with a reduction in plasma very low density lipoproteins, indicating that the hypolipidemic effect of OFS may be due to changes in liver lipid metabolism. We therefore tested whether OFS feeding modified the capacity of the liver to synthesize triglycerides from free fatty acids. Hepatocytes isolated from livers of control and OFS-fed rats were incubated in the presence of [1-14C]palmitate, and both intracellular and extracellular [14C]triglyceride formation were quantified. We found that chronic feeding of an OFS-supplemented diet to rats significantly reduced the capacity of isolated hepatocytes to synthesize triglycerides from palmitate. The results suggest that, like other soluble dietary fibers, OFS significantly alters liver lipid metabolism, resulting over time in a significant reduction in plasma triglyceride, phospholipid and cholesterol levels.

Analysis of Variance↗
PubMed1995

Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy digestive balance in the rat.

In the present study, we have assessed the apparent retention of gross energy, nitrogen and Ca, Mg, Fe, Zn and Cu in rats receiving a diet supplemented with fermentable fructo-oligosaccharides with high and low degree of polymerization. Feeding 10% Raftilose (degree of polymerization: 4.8) or 10% Raftiline (degree of polymerization: 10) decreased to the same extent (a) the fecal excretion of all the minerals, despite an increase in total fecal mass excretion leading to an improvement of the absorption of Ca, Mg, Fe and Zn; (b) total gross energy absorption; and (c) led to an increase in the faecal excretion and to a decreased urinary excretion of nitrogen, suggesting a displacement of part of nitrogen excretion towards the large intestine. Feeding fermentable fructo-oligosaccharides may thus constitute a good way to counteract syndromes resulting from hyperammonemia or disturbed Fe, Ca, Mg and Zn homeostasis.

Animals↗
PubMed1995

Protective effect of dietary fructo-oligosaccharide in young rats against exocrine pancreas atrophy induced by high fructose and partial copper deficiency.

The objective of this investigation was to protect rats against exocrine pancreatic atrophy by adding 22% fructo-oligosaccharide (FOS), a natural fructan obtained from inulin, to the 50% copper-deficient diets containing qualitatively and quantitatively different carbohydrates. Young male Wistar rats were maintained on these diets for 10 wk, being weighed weekly then killed and autopsied. Major organs were weighed and histologically examined. Copper content in the diets was measured by flame atomic absorption spectroscopy. Incomplete (50%) copper deficiency avoided precocious mortality due to cardiovascular lesions and enabled another pathological condition to develop, consisting of the induction of exocrine pancreas atrophy. Introduction of gradually increasing percentages of fructose in diets at the level of 22, 42 and 62% induced a gradual increase in the copper-deficiency-mediated pathology in rats, expressed by an increase in exocrine pancreatic atrophy. 22% FOS introduced to the diet prevented the pathology induced by both fructose and partial copper deficiency better than starch added to diet at the level of 20 or 40%.

Animals↗
PubMed1995

Determination of digestible energy values and fermentabilities of dietary fibre supplements: a European interlaboratory study in vivo.

The performance of methods to determine energy conversion factors for dietary fibre (DF) supplements and fermentability (D) values of their non-starch polysaccharides (NSP) was investigated. Heats of combustion, digestible energy (DE) and D values were determined on five DF supplements in five European laboratories on five separate occasions. In each instance the DF supplements were fed to juvenile male Wistar rats at two doses, 50 and 100 g/kg basal diet, for 3 weeks with food and faeces collected in the 3rd week. Among-laboratory variations in heats of combustion (delta Hc) were < 2%. DE values (kJ/g dry weight) at the upper and lower doses respectively were: 10.4 and 9.9 for a high-methoxyl apple pectin, 9.5 and 9.4 for a sugar-beet DF supplement, 12.2 and 12.7 for soyabean DF supplement, 3.8 and 4.0 for maize bran, and 0.3 and 0.3 for Solka-floc cellulose. Variations among laboratories, among occasions and among animals were < 1, < 2 and < 2.5 kJ/g respectively. The among-occasion: among-laboratory variance ratio for DE was 0.5, suggesting the method performed equally well in all laboratories. There was no evidence of learning of fatigue or fatigue in the performance of the method. D values were also independent of dose and at the high and lower doses were: pectin 0.92 and 0.95, sugar-beet NSP 0.68 and 0.68, soyabean NSP 0.86 and 0.88, maize bran 0.17 and 0.18, cellulose 0.07 and 0.06. Among-laboratory variance tended to increase with decreasing fermentability and ranged from 0.03 to 0.18. The DE and D data were not significantly different from a previously proposed relationship DE = 0.7 x delta Hc x D, where delta Hc is the heat of combustion of the supplement. We conclude that while the among-laboratory variation in the D of difficult-to-ferment NSP is too large for the reliable prediction of energy value the method for the direction determination of DE is both reproducible and repeatable, that DE is independent of dosage of DF supplement up to 100 g/kg diet, and that it is safe to discriminate between energy values with a precision of 3 kJ/g. The conversion of both DE and D to net metabolizable energy for the purpose of food labelling, tables and databases is described.

Animals↗
PubMed1994

Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by phenobarbital and nafenopin.

As previously demonstrated, chronic administration of phenobarbital (0.05% in the drinking water) and of nafenopin (0.1% in the diet) increases the incidence and the kinetics of appearance of liver cancers. If bile acids play a key role in liver carcinogenesis, it might thus be expected that treatments like phenobarbital or nafenopin, which positively modulate that process, also modify their hepatic pool. The aim of the present study was to analyze the modifications of the liver bile acid pool during the modulation of liver carcinogenesis by phenobarbital and nafenopin. The animals were submitted to the hepatocarcinogenic initiation-selection (IS) procedure adapted from Solt and Farber. As compared to basal diet, the chronic feeding of phenobarbital significantly increased the total concentrations of liver bile acids both at weeks 9 and 17. That increase was mainly due to a change in the concentration of beta-muricholic acid and hyodeoxycholic acid and, to a lesser extent, of chenodeoxycholic acid and alpha-muricholic acid. In contrast, feeding a diet containing nafenopin led to a significant decrease in the concentration of liver bile acids, due to a complete disappearance of chenodeoxycholic acid and muricholic acid, and a decrease in the concentration of hyodeoxycholic acid. Carcinomas appearing in IS phenobarbital-treated rats contain fewer bile acids than the surrounding parenchyma (because of the decrease in deoxycholic acid and ursodeoxycholic acid) whereas the malignant tumors appearing in IS nafenopin-treated rats have essentially the same pattern of bile acids as the surrounding parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Adenine nucleotides and inhibition of protein synthesis in isolated hepatocytes incubated under different pO2 levels.

Hepatocytes incubated at a pO2 of 0 mm Hg (N2/CO2, 95%/5%) loose their intracellular ATP content and their ability to synthesize RNA and proteins. Protein synthesis is virtually inhibited from the beginning of the incubation, while ATP content is gradually lost, thus suggesting a primary response of the cell to the absence of O2 rather than to ATP depletion. Such an early decrease of protein synthesis (as estimated as the incorporation of [14C]Leu into cell proteins) is unlikely the result of inhibition of amino acids uptake, enhanced protein degradation, or decreased RNA synthesis. Reoxygenation of such previously hypoxic cells with O2/CO2 at 95%/5% (pO2 of 700 mm Hg), leads to the recovery of both ATP and protein synthesis, even better the hypoxic period is not longer than 30 min. In hepatocytes incubated for 30 min under a pO2 of 700, 80, or 50 mm Hg, cell survival and ADP content are almost identical. Incorporation of radiolabelled leucine is linear in cells incubated under 700 mm Hg O2, but it rather stops at a pO2 of 80 or 50 mm Hg. The time course of both ATP and GTP content behaves in a similar way: it is fairly constant at a pO2 of 700 mm Hg, but a depletion is initiated after 20 min of incubation at a pO2 of 50 or 80 mm Hg. Finally, incubation of hepatocytes either at 700 or 0 mm Hg O2, in the presence of fructose (10 mM), shows that ATP content is maintained at the same level whatever the pO2 level. AMP content is increased only in cells incubated at 0 mm Hg O2 in the absence of fructose. Incorporation of radiolabelled leucine is stopped in such hypoxic cells incubated or not in the presence of fructose. From these results it appears that the presence or the absence of O2 might represent a turn on/off signal to which hepatocytes respond immediately by important metabolic changes like the inhibition of protein synthesis.

Adenine Nucleotides↗
PubMed1993

Identification of the free radical formed by addition of hydroxyl radical to dehydroalanine compounds.

N-substituted dehydroalanines, a class of compounds with both acceptor and donor substituents (ADs), react with and scavenge oxygen radicals. Interest in these compounds is based on their potential to lessen the cardiotoxicity of drugs with antineoplastic activity such as Adriamycin. The reactivity of these compounds with hydroxyl radical is evident from their inhibition of hydroxyl radical adduct formation. ESR spin trapping studies of the species formed by reaction of the AD series of compounds with the hydroxyl radical are reported here for the first time. ESR results show that hydroxyl radical attack on the capto-dative site of the AD compounds produces the predicted carbon-centered free radical.

Alanine↗
PubMed1993

Dietary fiber, inulin, and oligofructose: a review comparing their physiological effects.

Dietary fiber is a general term. It covers a wide variety of substances that belong to the family of carbohydrates that resist hydrolysis by human alimentary enzymes but are fermented by colonic microflora. The main physiological effects of dietary fiber are primarily on gastric emptying and small intestinal transit time, resulting in an improved glucose tolerance and a decreased digestion of starch: second, on colonic transit time and large bowel functions due to fermentation by ceco-colonic microbial flora or bulking action. The so-called soluble dietary fibers are fermented to a large extent by a wide variety of anaerobic bacteria that result in an increase in bacterial biomass, an increase in fecal mass, a change in intracolonic pH, and production of short chain fatty acids and various gases as metabolic end products. The insoluble fibers are only marginally fermented: they serve almost exclusively as bulking agents that result in shorter transit time and increased fecal mass. The short chain fatty acids resulting from the colonic fermentation of dietary fiber are largely absorbed via the portal blood and reach both the liver and the peripheral tissues. They induce changes in glucose and fat metabolism leading to post-prandial hypoglycemia and long-term hypolipidemia. Inulin and oligofructose are fructans with a degree of polymerization of 2 to 60 and 2 to 20, respectively. Due to the structural conformation of their osidic bridge (beta 2-1), they both resist the hydrolysis by human alimentary enzymes. Moreover, when reaching the colon, both inulin and oligofructose are almost quantitatively fermented almost exclusively by colonic bifidobacteria and bacteroides. Such an extensive fermentation causes an increase in fecal bacterial biomass, a decrease in ceco-colonic pH, and produces a large amount of fermentation products among which the short chain fatty acids that exert systemic effects on lipid metabolism. Thus, both inulin and oligofructose have most of the characteristics of a dietary fiber and the proposal is made to classify them as such. Moreover, they are bifidogenic factors, because, due to still unknown reasons, they are primarily fermented by bifidobacteria. It is concluded from this review that "nondigestible fructo-oligosaccharides," even though they are not included in the carbohydrate fraction that is quantified as dietary fiber by classic analytical methods, have most of the physiological effects of a dietary fiber.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

The biochemistry of oligofructose, a nondigestible fiber: an approach to calculate its caloric value.

Oligofructose, a natural food ingredient, is the product of partial enzymatic hydrolysis of inulin. This nondigestible oligosaccharide is fermented by colonic bacteria to produce mainly short-chain fatty acids, L-lactate, and CO2 and the energy necessary for bacterial growth. It also increases fecal mass. Based on biochemical balance charts for carbon atoms, metabolic pathways, and energy yield to the host, the caloric value of a fructosyl unit of oligofructose is calculated to be 25-35% that of a digested molecule of hexose. The caloric value of oligofructose is thus likely to be close to 1 kcal/g.

Animals↗
PubMed1993

Serum alkaline deoxyribonuclease activity, a sensitive marker for the therapeutic monitoring of cancer patients: methodological aspects.

Alkaline deoxyribonuclease (DNase) is present in human circulating serum but its physiological role and signification of its variations are still largely unknown. The present report demonstrates that between 37 degrees C and 50 degrees C, as measured in the presence of 0.25 mmol/l Ca2+ and 5 mmol/l Mg2+, serum alkaline DNase activity increases, in most sera, reaching a level far higher than expected from thermal activation. This observation is thought to be due to the thermal inactivation of a serum inhibitor of the enzyme, which limits its usefulness as a therapeutic marker. By measuring serum alkaline DNase activity at 50 degrees C, the authors have developed a clinical test which has been successfully applied to the therapeutic monitoring of patients with various types of cancers.

Biomarkers, Tumor↗
PubMed1991

Biochemical changes in isolated hepatocytes exposed to tert-butyl hydroperoxide. Implications for its cytotoxicity.

When isolated hepatocytes were exposed to tert-butyl hydroperoxide (tBOOH) they lost their cellular membrane integrity. Decreased levels of GSH, increased phosphorylase a activity (an indirect index of the amount of free cytosolic Ca2+), and increase in the formation of malondialdehyde (MDA)-like products (an index of lipid peroxidation) preceded the release into the culture medium of the cytosolic enzyme lactate dehydrogenase (LDH), indicating that this later process was the consequence of the former intracellular events. While ATP levels were not modified during the incubation of cells with increasing concentrations of tBOOH, protein synthesis was decreased in a concentration-dependent manner. The glycogen content decreased at the same time as the increase in LDH leakage. The addition of promethazine (PMZ) an antioxidant molecule, prevented the lipid peroxidation, but did not protect cells against the oxidative effects of tBOOH, including loss of membrane integrity. Nevertheless, the addition of GSH to cell suspensions incubated with tBOOH, decreased the formation of MDA-like products, restored the protein synthesis rate, prevented partially the activation of phosphorylase a and preserved cell viability. On the basis of these results, we postulate that both GSH depletion and modification in phosphorylase a activity (Ca2+ levels) were the most relevant intracellular events to explain the cytotoxicity of tBOOH.

Adenosine Triphosphate↗
PubMed1991

The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator.

Perfluorooctanoic acid (PFOA) is a peroxisome proliferator. The aim of this study was to test for its ability to act as a positive modulator of hepatocarcinogenesis, in the so-called biphasic (initiation by diethylnitrosamine 200 mg/kg ip followed by treatment with the suspected modulators) and triphasic (initiation by the same dose of diethylnitrosamine followed by a selection procedure for 2 weeks consisting of giving 2-acetylaminofluorene and in the middle of this treatment a single dose of CCl4 followed by treatment with the suspected modulators) protocols of liver carcinogenesis. In both protocols treatment with PFOA increased the incidence of malignant hepatocellular carcinoma (HCC). As compared to phenobarbital, the modulating effect of PFOA is more pronounced in a biphasic than in the triphasic protocol. In parallel with positive modulation of HCC, PFOA also selectively induced the peroxisomal acyl-CoA oxidase activity and, to a lesser extent, catalase activity.

Acyl-CoA Oxidase↗
PubMed1990

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers.

N-acyl dehydroalanines react with and scavenge mainly superoxide radical (O-2.) and hydroxyl radical (HO.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD50 at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.

Alanine↗
PubMed1990

N-acyl dehydroalanines scavenge oxygen radicals and inhibit in vitro free radical mediated processes.

N-substituted dehydroalanines react with and scavenge oxygen radicals. One of those compounds, the para-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-5, inhibits the reduction of ferricytochrome c by superoxide anion (O2-.). It can also inhibit the oxidation of linolenic acid, another chemical process, which is mediated by hydroxyl radical (HO.). Furthermore, microsomal lipid peroxidation induced by iron salts was also inhibited by AD 5, but with a different degree of efficacy. In fact, lipid peroxidation initiated by a ferrous-oxygen complex (as in iron/NADPH-dependent peroxidation) was inhibited by AD 5 in a range of concentration of 2-4 mM. On the contrary, iron/NADPH-independent lipid peroxidation, where alkoxy radicals (RO.) have principally been involved, was inhibited in a range of concentration of 6-10 mM. The ESR studies by using the spin trapping agent DMPO, show that AD-5 reacts with HO. with a second order constant of 2.8 X 10(9)-4.5 X 10(9) M-1 s-1.

Alanine↗
PubMed1990

AD 5, a dehydroalanine derivative, decreases the amount of reactive oxygen species formed during nitrofurantion microsomal metabolism.

N-acyl dehydroalanines have been shown to react with and scavenge oxygen derived free radicals. One of those compounds, the AD-5 (N-(paramethoxyphenylacetyl) dehydroalanine) has been examined for its ability to decrease the amount of reactive oxygen species which appeared when liver microsomes (isolated from rats pretreated with phenobarbital) are incubated in the presence of Nitrofurantoin (NF). This molecule was used as a model compound in order to stimulate the production of superoxide anion and hydrogen peroxide, as well as to enhance the oxidation of NADPH and the oxygen uptake. These two later parameters were not modified when adding AD-5 to microsomes incubated in the presence of NF. However, in such conditions the amount of both and hydrogen peroxide was decreased. These effects were dose-dependent. These data suggest that AD 5 inhibits the building up of superoxide and consequently the production of hydrogen peroxide. We postulate that AD-5 acting as an oxygen derived free radical scavenger, can be used to inhibit the oxidative injury induced by nitrofurantoin and other redox cycling drugs.

Alanine↗