Biomedical subjects

A Favier

Publications and source records attributed to A Favier.

At least 73 records · Page 4Linked to original sources

PubMed1998

Urine 8-oxo-7,8-dihydro-2-deoxyguanosine vs. 5-(hydroxymethyl) uracil as DNA oxidation marker in adriamycin-treated patients.

We measured the base 5-(hydroxymethyl) uracil (HMUra) and the nucleoside 8-oxo-7,8-dehydro-2'-deoxyguanosine (8-oxo-dGuo) in urine of adriamycin-treated cancer patients. Adriamycin has been shown to generate oxygen free radicals by various mechanisms. HMUra and 8-oxo-dGuo are two known lesions of DNA, produced by oxygen free reaction on thymine and 2'-deoxyguanosine, respectively. HMUra was measured by GC-MS/isotopic dilution and 8-oxo-dGuo by HPLC/EC, both after prepurification by semipreparative HPLC. Here we report the results of a study involving 20 cancer patients treated with flash doses of ADR. We found that urine HMUra is significantly increased (HMUra (nmol/24h): 80.8 8.44 vs. 98.7+/-6.87; p < 0.01) 24h after administration of the drug, while 8-oxo-dGuo did not show any significant variation. Urine HMUra seems to be a suitable short-term marker of DNA alterations by oxygen free radicals.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Background and rationale behind the SU.VI.MAX Study, a prevention trial using nutritional doses of a combination of antioxidant vitamins and minerals to reduce cardiovascular diseases and cancers. SUpplementation en VItamines et Minéraux AntioXydants Study.

The "SUpplementation en VItamines et MinérauxAntioXydants" (SU.VI.MAX) study is a randomized double-blind, placebo-controlled, primary prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 micrograms; and zinc, 20 mg), at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of major health problems in industrialized countries, and especially the main causes of premature death (cancers and cardiovascular diseases). The study involves 12,735 eligible subjects (women aged 35 to 60 years; men aged 45 to 60 years) included in 1994 in France. They will be followed up for 8 years. The objectives and the specific design of this intervention study are linked to its public health aim. The targeted population is the general population (not simply high-risk subjects) and the antioxidant agents tested are being administered at a level which is not pharmacologic and which may be attained by dietary intake of natural sources of these micronutrients and/or enriched foods. The amounts we are testing in the SU.VI.MAX study are those which, in observational studies have been associated with the lowest risk of diseases. This report presents the rationale and discusses the justification of the design, doses and combination of antioxidant micronutrients chosen in the SU.VI.MAX study.

Adult↗

PubMed1997

Presence of zinc and calcium permeant channels in the inner membrane of the nuclear envelope.

The nuclear envelope possesses specific ion channels that regulate the ionic traffic between the cytoplasm or the perinuclear space and the nucleoplasm. Using the patch-clamp technique to isolated rat nuclei exhibiting only the inner membrane of the nuclear envelope, we report the existence of calcium and zinc permeant channels. These channels displayed similar characteristics (conductance : 8 and 11 pS respectively, open time constant (3.5 ms and 3.7 ms) and close time constant (5.1 ms and 4.8 ms)) and were insensitive to different types of calcium channels blockers and to calcium concentration in the bathing solution. The exact role of these channels remains to define, but they may contribute to the regulation of intranuclear Ca++ or Zn++ dependent processes as important as cell proliferation or programmed cell death. Moreover, this work demonstrates that our nuclei preparation provides a way to study the inner membrane of the nuclear envelope.

Animals↗

PubMed1997

Selenium and antioxidant vitamin and lipidoperoxidation levels in preaging French population. EVA Study Group. Edude de vieillissement artériel.

Selenium (Se) and antioxidant vitamins might play an important role in the etiology of free radical-related diseases and aging. In the Edude de vieillissement artériel (EVA) study, we have determined the plasma thiobarbituric acid reacting substances (TBARS) as an indicator of free radical-induced lipid peroxidation, plasma selenium and carotenoids, and erythrocyte vitamin E levels in 1389 subjects aged 59-71 years. We also looked for an association between these parameters and cardiovascular risk factors in early elderly. The results show that plasma TBARS were significantly increased in elderly in comparison with values reported in younger adults. However, plasma Se and carotenoids as well as erythrocyte vitamin E in elderly people are close to those reported in adult people. If plasma Se showed no difference between men and women, the three other parameters were significantly higher in women than in men. With regard with cardiovascular risk factors, plasma TBARS were highly positively correlated with total and low-density lipoprotein (LDL) cholesterol in men and women. Plasma carotenoids were also positively correlated with plasma total cholesterol and LDL cholesterol in both sexes. Finally, plasma TBARS were highly correlated with smoking and alcohol consumption. In conclusion, this part of the EVA study shows that some cardiovascular risk factors, like smoking and cholesterol level, are associated with high free radical-induced TBARS levels in the preaging population, although plasma Se and carotenoids as well as erythrocyte vitamin E levels in elderly people were close to those reported in adult younger people.

Aged↗

PubMed1997

Involvement of zinc in intracellular oxidant/antioxidant balance.

The effect of zinc (Zn) on cellular oxidative metabolism is complex and could be explained by multiple complementary interactions. In this study, we evaluated the impact of Zn on the pro-oxidant/antioxidant balance of HaCaT keratinocytes. Cells were submitted to a diffusible metal chelator able to induce intracellular Zn deprivation, TPEN, in combination or not with Zn chloride (ZnCl2), in the culture medium. The intracellular amount of Zn, copper (Cu), and iron (Fe) was determined, as well as CuZnSOD and MnSOD activities and glutathione reserves. The consequence of the modulation of Zn concentration on lipid peroxidation was also evaluated. TPEN induced a significant dose-dependent decrease in intracellular Zn and Cu (from 394-181 and 43-21 microg/g protein, respectively, after 6 h of TPEN 50 microM). No significant change in intracellular Fe concentration was found following TPEN exposure. The SOD activities were unchanged after 6 h of TPEN 50 microM application, either CuZnSOD or MnSOD. Cells exposure to TPEN induced a deep time- and dose-dependent decrease in their glutathione content (from 65-8 microM/g protein after 6 h of TPEN 50 microM), and a concomitant increase in glutathione in the cell-culture supernatants. No significant change in lipid peroxidation products was detected.

Antioxidants↗

PubMed1997

Trace elements and protein-calorie malnutrition in the Fès area (Morocco).

Copper and selenium are essential micronutrients for development and growth as well as being necessary for the immune system and as an antioxidant defense. These trace elements present a variable distribution according to geographic regions. Several studies have shown reduced serum copper and selenium levels, as well as the activity of erythrocyte copper-zinc superoxide dismutase (SOD) and selenium-glutathione peroxidase (GPX) in protein-calorie malnutrition (PCM). The aim of this study was to evaluate the erythrocyte enzymatic activity depending on copper or selenium and the levels of these elements in serum. Fifty-six Moroccan children between the age of 6 to 60 months were selected, then divided into 20 control group children and 36 patients suffering from PCM (15 mildly malnourished and 21 severely malnourished). The malnourished group showed a significant decrease of selenium and copper levels that was related to the severity of malnutrition. Serum selenium decreased more than serum copper. No differences were noted between the groups in erythrocyte GPX activity, whereas SOD activity showed more discrepancy than in the copper levels in malnutrition. Serum copper or ceruloplasmin levels could be used as indicators of the severity of malnutrition, whereas the selenium levels could be used as indicators of the nutritional status.

Ceruloplasmin↗

PubMed1997

Fish oil effects on tissular fatty acids and plasma lipid peroxidation in zinc deficient rats.

Zinc has been reported to play a key role in lipid metabolism as well as in defences against oxidative stress. The aim of this work was to investigate the fatty acid distribution (plasma, heart, kidney, liver) and peroxidation (plasma) in zinc-deficient rats fed with n-6 fatty acids (10% corn oil) or n3 fatty acid fish oil (10% Maxepa). Zinc deficiency led to a decreased tissular and plasma n-6/n-3 ratio both in triglycerides and phospholipids. This effect was more marked in the Maxepa group than in the corn oil group. In plasma, the TBARs/TG + PL ratio was significantly enhanced in zinc-deficient animals, especially in rats receiving Maxepa. With regard to these results, zinc deficiency could appear as an aggravating factor of oxidative risk when associated with a n-3 fatty acid-rich diet. This work draws attention to the harmful oxidative risk associated with patients' intake of fish oil concentrate, without taking into account their antioxidant dietary intakes and status.

Animals↗

PubMed1997

Zinc and DNA fragmentation in keratinocyte apoptosis: its inhibitory effect in UVB irradiated cells.

Zinc has been shown to have antioxidant properties and to exhibit inhibitory effects on apoptosis. In this work we investigated the effect of zinc on DNA integrity and on apoptosis of HaCaT keratinocytes. Cells were submitted to zinc deprivation by a diffusible zinc chelator, (N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine) (TPEN) or supplied with zinc chloride and submitted to UVB radiation. After cell exposure to TPEN for 2 h, strand breaks significantly impaired DNA resistance to alkaline denaturation. DNA strand breaks induced by a 6 h TPEN application were significantly prevented if zinc chloride was supplied together with the chelator. TPEN also generated, after 4-6 h of application, cytoplasmic histone-associated DNA fragments (mononucleosomes and oligonucleosomes), features of cell death by apoptosis. Moreover, UVB irradiation led to early DNA strand breaks and to an increase in cytoplasmic nucleosomes which was maximum 10 h after irradiation. These effects were prevented by the supply of zinc chloride (0.1 mM) in the culture medium. These results suggest that zinc ions interfere with the apoptosis process at an early stage, by decreasing DNA damage able to trigger apoptosis.

Apoptosis↗

PubMed1997

Thiols and selenium: protective effect on human skin fibroblasts exposed to UVA radiation.

The sensitivity of human dermal fibroblasts to UVA radiation has been linked to a decrease in intracellular glutathione (GSH) levels. GSH (gamma-glutamyl-cysteinyl-glycine) is a radical scavenger and a cofactor for protective enzymes such as selenium-dependent GSH peroxidases. In this study, we examine the possibility of a cooperative interaction between three cysteine delivery systems and selenium in protecting human cultured fibroblast exposed to UVA radiation. Cells were irradiated (9, 15 and 20 J cm-2) following incubation with N-acetyl-cysteine (NAC, 5 mM), N-acetyl-homocysteine-thiolactone (citiolone (CIT), 1 mM) or L-2-oxothiazolidine-4-carboxylate (OTC, 1 mM). The modulation of the intracellular GSH levels by the addition of the different compounds was determined by enzymatic and separative methods. Cells were harvested for survival analysis by measuring the ability of the cell to adhere and proliferate. Treatments with NAC and CIT resulted in a significant rise in GSH levels compared with control cells, with protection against UVA radiation. OTC did not induce any rise in GSH level; nevertheless, the protective effect afforded by OTC is similar to that observed with NAC and CIT. Moreover, selenium (0.1 mg 1-1), as sodium selenite, significantly increased the protective efficiency of NAC and CIT, but not of OTC. Although the precise mechanism is not known, thiol molecules can inhibit the deleterious effects of UVA radiation. These results provide evidence that compounds capable of inducing GSH synthesis can act with selenium to protect cells against UVA damage.

Acetylcysteine↗

PubMed1997

Effect of increased fruit and vegetable intake on the susceptibility of lipoprotein to oxidation in smokers.

OBJECTIVE: To evaluate the effect of an increased dietary intake of fruit and vegetables on susceptibility of LDL to oxidation in smokers and nonsmokers. DESIGN: A descriptive and prospective study. SETTING: Joseph Fourier University, Grenoble. SUBJECTS: Volunteers were age and sex matched in the smoking and nonsmoking groups and were recruited by announcement. INTERVENTIONS: Increased intake of fruits and vegetables for two weeks providing 30 mg/day of carotenoids. MAIN OUTCOME MEASURES: Circulating levels of beta-carotene, lutein, lycopene, alpha-tocopherol; susceptibility of LDL to oxidation. Cu-Zn superoxide dismutase (Cu-Zn SOD), and Se glutathione peroxidase (Se-GSH-Px) activities and reduced (GSH) and oxidized (GSSG) glutathione. RESULTS: At entry (week 0: W0) smokers exhibited a lower plasma carotene level but the plasma parameters of oxidative stress and LDL oxidizability were not different from nonsmokers. After two weeks of increased intake of fruits and vegetables the circulating levels of carotenoids increased in smokers 23% and 11% in nonsmokers. At the same time the resistance of LDL to oxidation increased by 14% in smokers (P < or = 0.05) and by 28% in nonsmokers (P < or = 0.025). The mean whole blood GSH level was higher in smokers at entry but returned to a concentration similar to nonsmokers at the end of the study. CONCLUSION: This pilot study indicates that an increased, carotenoid rich food intake through its inhibitory effect on the susceptibility of LDL to oxidation may be an interesting approach to reduce the risk of atherosclerosis both in smokers and nonsmokers.

Adult↗

PubMed1997

The sizes of the exchangeable pools of selenium in elderly women and their relation to institutionalization.

Exchangeable pools of Se after an intravenous injection of 74Se-enriched isotope as sodium selenite were measured in two groups (n 9) of elderly women (free-living aged 64-82 years and institutionalized aged 68-82 years), and a comparison group (n 9) of young women aged 31-40 years to evaluate the effect of age and institutionalization on Se reserves. Dietary Se intake was not different among the three groups. Plasma Se and glutathione peroxidase (EC 1.11.1.9) levels were significantly lower in the institutionalized elderly women (P < 0.05). In each of the three groups, two pools were determined from our model. The size of the first pool and the sum of the two pools were lower in the group of institutionalized elderly women than in the other two groups. The significant correlation between plasma Se level and total Se pool size (r 0.66, P < 0.01) indicated that this last variable could serve as a new marker of Se status. Finally, these data suggest that the Se status of elderly women is more related to lifestyle, in terms of institutionalization or not, than to age per se.

Adult↗

PubMed1997

Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59-71 y: The EVA Study. Etude sur le Vieillisement Artériel.

There are few epidemiologic studies of the effects of lipid peroxidation and antioxidant status on atherosclerosis. The relation of lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBARS) and biological markers of antioxidant status to ultrasonographically assessed carotid atherosclerosis was examined from baseline data of a longitudinal study on cognitive and vascular aging (Etude sur le Vieillisement Artériel, the EVA Study). The study sample was composed of 1187 mean and women aged 59-71 y without any history of coronary artery disease or stroke. Ultrasound examination included measurements of intima-media thickness (IMT) on the common carotid arteries (CCAs) and at the site of plaques. After adjustment for conventional cardiovascular risk factors, erythrocyte vitamin E was significantly and negatively associated with CCA-IMT in both men and women whereas plasma selenium and carotenoids were not. No association was found between TBARS and CCA-IMT in either sex. However, TBARS were significantly higher in men with carotid plaques than in those without. This association was strengthened in men with concentrations of erythrocyte vitamin E, plasma selenium, and carotenoids below the lowest quartile. Our findings give some epidemiologic support to the hypothesis that lipid peroxidation and low antioxidant status are involved in the early phases of atherosclerosis.

Aged↗

PubMed1997

Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets.

The purpose of this study was to investigate the effects of vitamin E in rats fed a high fructose diet which leads to insulin resistance, on some components of the free radical defense system and on insulin sensitivity. The rats (postweaning, 50 g) were divided into three groups: the control group (C, n = 16), which received a purified diet containing 60 g/100 g carbohydrates, the high fructose-fed group (FT, n = 16),fed a diet in which 56.8% of the carbohydrate as fructose, and a high fructose and vitamin E-fed group (FVE, n = 16), fed the FT diet supplemented with 3.4 g vitamin E/kg diet (vs. 0.17 g/kg in C and FT groups). The duration of the treatment was 6 wk. Insulin sensitivity was determined in half of the rats in each group using the euglycemic hyperinsulinic glucose clamp technique. The remaining rats were investigated for plasma glucose, insulin, triglyceride and fructosamine concentrations and for components of the free radical defense system. The FT group had a significantly lower insulin sensitivity than the C group. Basal glycemia was not different among the groups. In comparison with the C group, the FT group had a greater lipid peroxidation, as indicated by the higher concentrations of plasma thiobarbituric acid reactive substances (TBARS) and blood disulfide glutathione (GSSG) and the lower Cu-Zn superoxide dismutase (Cu-Zn SOD) activity. These markers approached the values of the controls after addition of vitamin E. Moreover, the FVE group had a higher insulin sensitivity than the FT group, but it remained lower than in the C group. These results show that a high fructose diet in rats leads to insulin resistance and a defect in the free radical defense system. Vitamin E supplementation improves insulin sensitivity in fructose-fed rats.

Animals↗

PubMed1997

[Evaluation of oxidative stress and antioxidant defences in malnourished Moroccan children].

In Morocco, malnutrition is a public health problem. Indeed, 25% of 6- to 60-month-old children suffer from malnutrition. Imbalance between antioxidant protection and prooxidant stress has been reported to accurately predict the survival of malnourished children. Therefore, we determined blood antioxidant vitamins (retinol, alpha-tocopherol and carotenoids), trace elements (serum zinc, copper and selenium) and enzymes (erythrocyte Se glutathione peroxydase and Cu-Zn superoxide dismutase) as well as blood oxidative stress index [ferritine, thiobarbituric-acid reactants (TBARS)] in 21 children suffering from severe malnutrition, 15 children suffering from mild malnutrition and in 20 healthy control children. Selenium, retionol, alpha-tocopherol and carotenoids were significantly decreased in malnourished children. These decreases were related to the severity of malnutrition. Moreover, the percentage of vitamin and trace element concentrations under deficient cutoff were high in malnourished children. On the contrary, TBARS, ferritin and prognostic inflammatory and nutritional index (PINI) were significantly increased in malnourished children. Except for TBARS, these increases were related to the severity of malnutrition. On the other hand, blood retional, alpha-tocopherol, beta-carotene and selenium were negatively related to alpha 1-acid glycoprotein. Blood beta-cryptoxanthin, lycopene, carotenes and copper were positively related to weight. Finally, blood lutein/zeaxanthin and copper were positively related to height. These results confirm the imbalance between antioxidant protective factors and oxidative stress index in malnourished children. Moreover, the decrease in antioxidant protective factors is related to inflammation or stature. These results suggest that antioxidant micronutrient supplementation of the refeeding diet could be required in the nutritional rehabilitation of malnourished children.

Antioxidants↗

PubMed1997

[Dynamic phototherapy: study of anti-tumour potentialities of bis (tri n-hexylsiloxy) silicon phthalocyanine on malignant achromic M6 melanocytes. EPR study of phototoxic mechanism].

Photodynamic therapy of cancerous cells is a technique relying upon the irradiation of tumorous cells after selective incorporation of a photosensitizer. The bis (tri n-hexylsiloxy) silicon phthalocyanine is a second generation photosensitizer. Anti-cancerous potentialities of this molecule have been evaluated against the melanotic M6 cell line. Results have evidenced a high phototoxicity at low concentration and no dark toxicity under the same conditions. EPR studies on the photochemical pathways involved in phototoxicity processes have been realised in solvent and model membranes (liposomes). Results provide evidences for the production of singlet oxygen (1O2) as well as superoxide (02(o)-) and hydroxyl radicals (0OH).

Antineoplastic Agents↗

PubMed1997

Lipid peroxidation level and antioxidant micronutrient status in a pre-aging population; correlation with chronic disease prevalence in a French epidemiological study (Nantes, France).

OBJECTIVE: The general objective of the Etude du Viellissement Arterial (EVA) program is to follow vascular aging and the decline in cognitive functions at the cerebrovascular level longitudinally over a 4-year period. One of the specific objectives of this EVA study is to examine epidemiologically the relationship between the markers of oxidative stress (lipid peroxidation), the antioxidant micronutrient status (particularly of selenium, vitamin E, and the carotenoids) and the prevalence of chronic disorders occurring during the pre-aging period. METHODS: 1389 subjects aged from 59 to 71 years were studied. RESULTS: The concentration of plasma lipid peroxides was higher than in young adults (2.91 +/- 0.38, men; 2.97 +/- 0.40, women (mumol/l). On the other hand, plasma Se (1.09 +/- 0.21, men; 1.10 +/- 0.19, women (mumol/l)), erythrocyte vitamin E (5.32 +/- 1.29, men; 5.52 +/- 1.28, women (mumol/l)), and total plasma carotenoids (2.19 +/- 0.98, men; 3.07 +/- 1.33, women (mumol/l)) were comparable to values in young adults. In our cohort, 40% of subjects had unremarkable medical histories. The disorders most often encountered were lipemia (29.8% of men, 36.1% of women), and hypertension (28.9% of men, 30.4% of women). CONCLUSION: Se and vitamin E levels were raised in cases of lipemia, especially in those treated with fibrates. The mechanism of the increase is unknown. In hypertensives and diabetics, there was a decrease in total carotenoids associated with increased peroxidative risk.

Aged↗

PubMed1997

Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX.

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.

Aged↗

PubMed1997

Dietary magnesium intake in a French adult population.

Magnesium intake was assessed using six 24-h dietary records during a 1-year period in 5,448 subjects (3,111 women 35-60 yrs old and 2,337 men 45-60 yrs old) in the SU.VI.MAX cohort, selected at a national level in France. The overall mean dietary intake was estimated at 369 +/- 106 mg/day in men and 280 +/- 84 mg/day in women. 77 per cent of women and 72 per cent of men had dietary magnesium intakes lower than recommended dietary allowances; 23 per cent of women and 18 per cent of men consumed less than 2/3 of these RDA. A strong positive correlation existed between energy and magnesium intake (r = 0.79; p < 10(-4)). Slight variations were observed according to socio-professional and educational levels and place of residence. Cereal products represented the main contribution in both men (21 per cent) and women (19.8 per cent). In men, the second source was represented by alcoholic beverages (11.7 per cent), which were a lower source of magnesium in women (5.5 per cent). Dairy products, vegetables, meat and poultry were the other main sources of dietary magnesium intake.

Adult↗