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Biomedical subjects

A Favier

Publications and source records attributed to A Favier.

At least 19 recordsLinked to original sources
PubMed1996

5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients.

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Adult↗
PubMed1996

Increase in glutathione peroxidase activity in malaria parasite after selenium supplementation.

Glutathione peroxidase (GPx), a key enzyme involved in the detoxification of many peroxides, has been investigated in two malaria parasite species: P. yoelii in vivo (murine malaria) and P. falciparum in vitro (human malaria). We demonstrate the presence of an endogenous GPx activity in these two Plasmodia species. Enzymatic assays and the use of specific substrates and inhibitors allowed us to determine that the activity is selenium dependent. As this activity was shown to be lower in P. falciparum than in P. yoelii, and selenium levels were found to be low in culture medium and culture red blood cells, we hypothesized that a severe selenium deficiency could be responsible for this difference. After selenium supplementation, with either sodium selenite or selenocystine, we observed an increase in growth of P. falciparum only in with sodium selenite, whereas higher GPx activities were noted in parasites grown in media supplemented with both. An increase in GPx activities was also observed in parasites that had undergone an experimental oxidative stress with TBOOH. As the erythrocyte is unable to synthesize new proteins, these results provide further evidence for the existence of an endogenous parasitic selenium-dependent glutathione peroxidase.

Animals↗
PubMed1996

Effect of selenium supplementation on biological constants and antioxidant status in rats.

Oxygen-derived free radicals are currently suspected to be widely involved in the aetiology of several clinical disorders. In animals as well as in man, antioxidant trials are often undertaken to prevent oxidative stress. Among antioxidant molecules selenium has been largely studied. This study shows that plasma Se level is not a good index of Se status in the organism, at least at high levels of selenium. Red blood cell Se seems to be a more reliable index of Se status and could replace plasma Se level in the supplementation trials both in animals and humans. Se supplementation did not result in a significant decrease in oxidative stress markers as evaluated by blood and tissue malondialdehyde contents in healthy animals. Furthermore, heart function was altered and plasma Alanine aminotransferase activity was significantly increased in the selenium-supplemented group, which could reflect a slight subtoxic effect of selenium supplementation at the level used here. In view of the results presented, the maximum selenium content in animal diet in selenium supplementation experiments should not be higher than 2 mg/kg.

Animals↗
PubMed1996

Analyzed dietary intakes, plasma concentrations of zinc, copper, and selenium, and related antioxidant enzyme activities in hospitalized elderly women.

OBJECTIVE: The purpose of the study was to assess the actual dietary intakes of zinc (Zn), copper (Cu) and selenium (Se) intakes in relation with some indicators of trace element status in a selected group of hospitalized elderly patients. SUBJECTS: 24 elderly women aged 76-99 years were recruited in the Geriatric Department of the Grenoble University Hospital. MEASURES OF OUTCOME: Zn, Cu, and Se dietary intakes were estimated by duplicate portion analysis. Plasma trace element concentrations, Cu-Zn superoxide dismutase (Cu-Zn SOD) and Se glutathione peroxidase (Se GSH-Px) activities were determined in parallel. RESULTS: Mean daily intakes of Zn (5.6 mg), Cu (0.67 mg), and Se (23 micrograms) were low, in relation with poor energy intake and nutrient densities. Zn and Se levels in plasma were lower and plasma Cu increased compared to reference values obtained from healthy younger subjects. Thirty-eight percent of the elderly patients had plasma Zn concentrations < 10.7 mumol/l, but Cu status appeared adequate as suggested by the lack of decline in Cu-Zn SOD activity. A high proportion of plasma Se concentrations < 0.76 mumol/l and the parallel decrease in erythrocyte and plasma GSH-Px activities suggest a Se deficiency in this population. CONCLUSION: Our findings indicate that French hospitalized elderly patients may be at risk of Zn and Se marginal status and present altered antioxidant defenses in relation with low dietary intakes. It underlines the interest of supplementation studies in this population.

Aged↗
PubMed1996

Rapid high-performance liquid chromatographic assay for salicylic acid in plasma without solvent extraction.

The in vivo measurement of highly reactive free radicals, such as the hydroxyl radical (oOH), in humans is very difficult, if not impossible. Specific markers, based on the ability of oOH to attack aromatic molecules and produce hydroxylated compounds, are under investigation. In vivo radical metabolism of salicylic acid produces two main hydroxylated derivatives: 2,3- and 2,5-dihydroxybenzoic acid (DHBA). The measurement of 2,3-DHBA, following oral administration of salicylic acid or its acetylated form (aspirin), is proposed for the assessment of in vivo oxidative stress. The intensity of oxidative stress is a function of the ratio of dihydroxylated derivatives to salicylic acid rather than the absolute dihydroxylated derivatives levels. Consequently, a simple, accurate, and sensitive assay of the salicylic acid level in plasma is needed to investigate the in vivo free radical production. In this work, a rapid and sensitive method is presented that is useful for the quantitation of salicylic acid in biological fluids. The methodology uses high-performance liquid chromatography with spectrophotometric detection for the identification and quantitation of salicylic acid without organic extraction. A detection limit of less than 5 mumol is achieved with spectrophotometric detector responses that are linear over at least 6 orders of magnitude. Plasma concentrations of salicylic acid determined by the present technique are reported following the administration of 1000 mg aspirin in 20 healthy subjects.

Chromatography, High Pressure Liquid↗
PubMed1996

Photodynamic effects of hypericin on lipid peroxidation and antioxidant status in melanoma cells.

Photodynamic-induced cytotoxicity by hypericin (HYP) was studied on three human melanoma cell lines: one pigmented cell line (G361) and two amelanotic cell lines (M18 and M6). No significant variation in the rate of uptake and in the maximum level of HYP incorporation for the different cells was observed. In the dark, no cytotoxicity was observed in the range 0-10-6 M HYP for the three cell lines. Amelanotic cells were found to be more sensitive than pigmented cells to irradiation of HYP with visible light (lambda > 590 nm). In addition, for the three cell lines HYP-induced photocytotoxicity was found to be drug-dose and light-dose dependent. Under the conditions used, thiobarbituric acid-reacting substances (TBARs) were significantly increased in amelanotic cells after irradiation (P < 0.0001). By contrast, the amount of TBARS remained unchanged in pigmented cells. Antioxidant defenses including enzymes and glutathione (GSH) were assayed before and after HYP photosensitization. Significantly increased total SOD activity was observed after photosensitizaton for amelanotic cells (P < 0.05), while glutathione peroxidase (GSHPx) and catalase (Cat) activities but also GSH levels were significantly decreased (P < 0.01). In pigmented cells a significantly increased Cat activity was found (P < 0.05), whereas GSHPx was unaffected after irradiation. It can be inferred that (a) HYP may be an effective PDT agent for melanoma and (b) there is a relationship between melanin content and sensitivity to HYP phototoxicity in human melanoma cells.

Anthracenes↗
PubMed1996

Micronutrient status in elderly people. Geriatrie/Min. Vit. Aux Network.

A biochemical assessment of the vitamin and trace element status of 756 institutionalized elderly men and women, 66-103 years old (average 83.5 +/- 7.6 y), was conducted in 26 nursing homes in different areas of France. Serum concentrations of beta- and alpha-carotene, beta-cryptoxanthin, lycopene, retinol, alpha- and gamma-tocopherol, vitamin C, zinc and selenium were measured. A difference in biochemical markers according to sex was observed for vitamins E and C: elderly women had higher levels of alpha-tocopherol and vitamin C than elderly men. When expressed as a ratio of cholesterol, the difference between sexes for alpha-tocopherol disappeared. Simple regression analysis showed that most vitamins and trace elements were significantly negatively correlated with age. A high prevalence of low concentrations of vitamin C, zinc and selenium was revealed.

Aged↗
PubMed1996

Effect of 6 month supplementation with different combinations of an association of antioxidant nutrients on biochemical parameters and markers of the antioxidant defence system in the elderly. The Geriatrie/Min.Vit.Aox Network.

OBJECTIVES: To study the effect of supplementation with an association of small physiological amounts of antioxidant nutrients upon biochemical parameters and indicators of oxidative stress and antioxidant enzymes. DESIGN: The study included a double-blind placebo-controlled design. SETTING: Nursing homes in different areas in France. SUBJECTS: 575 elderly long term hospitalized subjects aged 65-103 years. INTERVENTION: Four groups were compared. They received daily: (V) vitamins (vitamin E, 15 mg and vitamin C, 120 mg) and beta-carotene, 6 mg; (T) trace elements (zinc, 20 mg, selenium, 100 micrograms); (VT) vitamins associated with trace elements; or (P) a placebo. Biological markers of vitamin and trace element status, and free radical parameters were measured initially and after 6 months of supplementation. RESULTS: An analysis of variance indicated a significant effect of vitamin supplementation on serum alpha-tocopherol, beta-carotene and vitamin C, a significant effect of trace element supplementation on serum zinc and both a significant trace element and a vitamin-trace element interaction on serum selenium. We observed significant effects of both trace element and vitamin supplementation on GPx activity (P < 0.01), an effect of vitamin supplementation on SOD activity (P < 0.05). CONCLUSION: Our results indicate that short-term supplementation with moderate doses of antioxidant vitamins and trace elements in elderly subjects clearly improves both non-enzymatic (alpha-tocopherol, beta-carotene, vitamin C) levels and enzymatic antioxidant (GPx and SOD) activity.

Aged↗
PubMed1995

High-performance liquid chromatography-electrochemical determination of salicylate hydroxylation products as an in vivo marker of oxidative stress.

The in vivo measurement of highly reactive free radicals, such as hydroxyl radical (.OH), in humans is very difficult if not impossible. Specific markers are currently under investigation (amino acid hydroxylatin, protein, DNA adducts, and aromatic probes). They are based on the ability of .OH to attack aromatic molecules to produce hydroxylated compounds that can be measured directly. In vivo, radical metabolism of salicylic acid produces two main hydroxylated derivatives, i.e., 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-DHBA). The measurement of 2,3-DHBA, following oral administration of salicylate or its acetylated form (aspirin), has been proposed for assessment of in vivo oxidative stress. In this work, a sensitive method for the detection of in vivo .OH generation is presented. The methodology employs a high-pressure liquid chromatography with electrochemical detection for the identification and quantification of the hydroxylation products from the reaction of .OH with salicylate. A detection limit of less than 0.1 pmol for the hydroxylation products has been achieved with electrochemical detector responses which were linear over at least five orders of magnitude. Using this technique, we measured plasma levels of 2,3- and 2,5-DHBA and dihydroxylated derivatives/salicylic acid ratios following the administration of 1000 mg aspirin in 20 healthy subjects. In the same individuals, plasma levels of thiobarbituric acid reactants (TBARs), a major index of lipid peroxidation, were also measured and correlation with hydroxylated products was sought. The plasma level of TBARs was positively correlated with the 2,5-DHBA/salicylic acid ratio, but not with the absolute plasma level of 2,3-DHBA.

Adult↗
PubMed1995

Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients.

Lipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 micrograms of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease.

Adolescent↗
PubMed1995

Copper, iron, manganese and zinc contents in human colostrum and transitory milk of French women.

Copper, iron, manganese and zinc were measured in breast milk samples collected from 82 healthy lactating mothers. Samples were collected from day of delivery to 7 days postpartum. Zn was analysed by flame atomic absorption spectrometry and the other elements by electrothermal atomic absorption spectrometry. Copper concentrations remained constant. Iron declined from 14.2 +/- 7.3 mumol/l at day 1 to 5.6 +/- 3.1 mumol/l at day 5 postpartum. Zinc and manganese declined from a maximum at 2 days postpartum (Zn: 183 +/- 70 mumol/l; Mn: 218 +/- 102 nmol/l) to 77 +/- 22 mumol/l (Zn) and 62 +/- 29 nmol/l (Mn) at 6 days postpartum. Copper concentrations are related to parity (r = 0.317, P < 0.001) and mother body mass index (r = 0.324, P < 0.001).

Adult↗
PubMed1995

Influence of a long-term zinc-deficient diet on rat platelet function and fatty acid composition.

A reduced zinc intake is associated with numerous abnormalities and, in particular, with hemostasis dysfunction. In this report, we studied the effects of a long-term dietary zinc restriction on platelet function. Three groups of rats were analyzed: a zinc-deficient group (ZD) and two zinc-adequate fed groups, one pair-fed (PF) and one ad libitum fed (AL). We found that ZD diet (0.2 p.p.m.) impaired ADP-induced aggregation of washed platelet after 4 and 8 weeks of diet. Thrombin-induced aggregation was impaired in ZD rats and PF rats after 8 weeks. The thrombin-induced mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids was followed as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products. Stimulated platelets of ZD rats exhibited a decreased production of cyclooxygenase and lipoxygenase products, particularly after 8 weeks of diet. Moreover, platelet thromboxane generation was decreased in the ZD group as studied using a radioimmunoassay after thrombin stimulation. In addition, we measured the total fatty acid compositions of platelet and plasma. As a whole, 20:5 (n - 3) and 22:5 (n - 3) fatty acids content were significantly increased in platelet lipids after 8 weeks. On the other hand, it is known that enrichment of these fatty acids through dietary studies, both in animal and human as well as in vitro incorporation in platelets, resulted in an inhibition of platelet function. Consequently, these changes in platelet membrane fatty acid composition may contribute to the impaired platelet aggregation observed in ZD rats.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1995

Interactions related to trace elements in parenteral nutrition.

Trace elements (TE) are now commonly added into the nutritive admixtures used in total parenteral nutrition (TPN) to prevent deficiencies which can be observed in patients undergoing long-term intravenous feeding. Although the needs in TE are not exactly known during a TPN, some of them must be considered as essential according to the results of studies dealing with general nutritional deficiencies. Among essential TE copper, iron and zinc are found at relatively high levels in organism. Chromium, manganese and selenium are also very important even though they are present at lower levels. In the case of a parenteral nutrition, the composition of the mixture is precisely defined and both digestion and absorption steps are shunted. Nevertheless, beneficial and/or negative physicochemical and metabolic interactions can occur between TE and the other nutrients. These interactions must be studied and taken into account because they can modify the bioavailability of the trace elements. In this article, our aim is to review the main recent bodies of knowledge which could be helpful to understand and prevent nutritional problems linked to these interactions during parenteral nutrition.

Animals↗
PubMed1995

Assessment of radical activity during the acute phase of myocardial infarction following fibrinolysis: utility of assaying plasma malondialdehyde.

Numerous experimental and clinical studies have reported a role of radical forms of oxygen in the etiology of the manifestations of reperfusion of the ischemic myocardium. However, clinical results remain controversial. The aim of this study was to ascertain the existence of reperfusion-related radical stress after thrombolysis with a marker that is easy to use and reliable. Thirty patients hospitalized for acute myocardial infarction were involved in the study. Of these, 18 had been subjected to intravenous thrombolysis (Group I) and 12 had not (Group II). They were compared to two control groups who had no history of myocardial infarction. Of these, 16 were patients with coronary heart disease hospitalized for stable angina (Group III) and 17 were patients free of any known cardiovascular disease (Group IV). Radical activity was assessed in plasma samples taken from a peripheral vein over a 10-day period of hospitalization by measuring (1) malondialdehydes (MDA) concentrations using fluorometry techniques or HPLC, (2) the antioxidant activity of glutathione peroxidase (GPx) and (3) the concentration of various antiradical compounds (beta-carotene, vitamins A and E, uric acid). All patients in Group I had a patent artery on coronary angiography and showed a significant increase in plasma MDA when compared to those who had not been subjected to thrombolysis (3.15 +/- 0.62 and 2.70 +/- 0.40 mole/l of plasma, respectively). Furthermore, GPx plasma activity was also significantly increased following thrombolysis. By contrast, there was no significant alteration in the antiradical compounds measured. These data suggest that MDA measurements (an early measurement 1-2 days and a late measurement 5-7 days after reperfusion) by fluorometry is a good marker of radical stress during reperfusion in man. The assessment of this marker in patients might represent a simple and reliable test of reperfusion efficacy following thrombolysis, and it might enable one to test the effect of various antioxidant therapies associated with thrombolytic treatment.

Aged↗
PubMed1995

Photodynamically induced cytotoxicity of hypericin dye on human fibroblast cell line MRC5.

The possible application of hypericin (hyp) in the photodynamic therapy (PDT) of cancer was investigated using the human fibroblast cell line MRC5. In aerobic conditions, at pH 7.4, irradiation of MRC5 cells was carried out with different doses of visible light and different doses of hyp. A low concentration of hyp (5 x 10(-9) M) was highly toxic to MRC5 cells, producing 15% survival for an irradiation period of 40 min. In the dark, no cytotoxicity was observed in the range 10(-9)-10(-7) M hyp. The mechanism of cell killing by hyp was also examined. Significant inhibition of MRC5 killing was observed on addition of 1,4-diazabicyclo[2,2,2]octane (DABCO) or histidine, known quenchers of type II mechanisms. In addition, the photodynamic effect of hyp was enhanced by deuterium oxide. The addition of desferrioxamine, catalase or superoxide dismutase (SOD), known scavenging agents of the type I mechanism, had a significant inhibitory effect on the rate of photodynamic action of hyp. The experimental results suggest that hyp has considerable potential for use as a sensitizer in the PDT of cancer.

Anthracenes↗
PubMed1995

Relationship between severity of ischemia and oxidant scavenger enzyme activities in the isolated rat heart.

It is currently believed that reperfusion injury of the ischemic or hypoxic myocardium can be attributed, at least in part, to an overproduction of reactive oxygen species (ROS). The aim of the present study was to determine whether ischemia (of different severity or duration) followed by reperfusion can affect the activity of endogenous scavenger enzymes in isolated perfused rat hearts. Isolated Langendorff perfused rat hearts were subjected to either total (10, 20 or 30 min; zero-flow) or partial (30, 60 or 90 min; low-flow of 0.10 or 0.35 ml/min) ischemia, followed by 10 min of reperfusion. Enzymatic activities of total superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were determined in cardiac tissues at the end of the perfusion protocol. Basal scavenger enzyme activities measured in control hearts (perfused under normoxic conditions) were 33.90 +/- 4.88, 31.20 +/- 5.32 and 1.61 +/- 0.29 IU/mg protein (mean +/- SD, n = 6 per group) for SOD, catalase and GPx respectively. Our results indicate that neither total SOD, GPx, nor catalase myocardial activities were changed whatever the perfusion protocol followed. The present study shows that the endogenous pool of catalytic ROS scavengers is not dramatically altered during ischemia or upon reperfusion. This suggests that ROS scavengers are not directly involved in the development of ischemia/reperfusion injuries. These results also support the premise that excessive radical generation does not occur in this model, where the isolated heart is subjected to ischemia.

Analysis of Variance↗
PubMed1995

Effect of dietary antioxidant trace element supply on cardiac tolerance to ischemia-reperfusion in the rat.

Over a 10-week period, female Wistar rats received a diet containing various levels of four trace elements (Zn, Cu, Mn, Se), co-factors of antioxidant enzymes (superoxide dismutase SOD, glutathione peroxidase GPx), in order to examine the influence of supplementation or deficiency of these elements (i) on tissue antioxidant enzyme defence systems, and (ii) on the susceptibility of the myocardium to ischemia-reperfusion injury. At the end of the dietary treatment, hearts were perfused at constant flow (11 ml/min) before being subjected to 15 min of total global normothermic ischemia, followed by reperfusion. The effects of the various diets (deficient, standard or supplemented) were estimated by studying functional recovery of various cardiac parameters (left ventricular developed pressure LVDP, dP/dtmax, heart rate x LVDP) as well as ultrastructural tissue characteristics. Furthermore, SOD and GPx activities were measured before ischemia and at the end of the reperfusion period. Results suggest that: (a) the activity of antioxidant enzymes increased or decreased significantly when diet was respectively supplemented with, or deficient in, trace elements, but was not further modified by an ischemia-reperfusion episode: (b) the recovery of cardiac function during reperfusion, and ventricular myocardial ultrastructure were significantly improved under the influence of trace element supplementation when compared to both standard and deficient groups. These results illustrate the protective effect of trace elements which are co-factors of antioxidant enzymes in limiting ischemia-reperfusion induced injury, and suggest a possible use in the field of anti-ischemic therapy.

Administration, Oral↗