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Biomedical subjects

A Favier

Publications and source records attributed to A Favier.

At least 145 records · Page 8Linked to original sources
PubMed1993

Effect of zinc deficiency on lipid peroxidation status and infarct size in rat hearts.

The objective of this study was to investigate the effect of dietary zinc on endogenous production of lipid peroxides, and on myocardial infarct size in rats. Male rats were fed a zinc-deficient diet containing 4 ppm zinc, or a standard diet containing 60 ppm zinc. After 3 weeks of diet, half of the animals underwent occlusion of the left coronary artery. The remaining animals underwent sham operation without occlusion. Forty-eight hours later, the hearts were sampled and lipid peroxide levels and infarct size were evaluated. Coronary occlusion was associated with an increase in cardiac lipid peroxide levels which were more pronounced in the zinc deficient group. However, infarct size appeared to be independent from zinc deficiency, despite the free radical-mediated lipid peroxide augmentation reported here. The pharmacological limitation of infarct size in rats with permanent coronary occlusion is discussed.

Animals↗
PubMed1993

Protective effect of selenium and zinc on UV-A damage in human skin fibroblasts.

Ultraviolet A radiation participates in cytotoxicity and carcinogenesis of the skin by a mechanism involving the generation of reactive oxygen species. Endogenous antiradical defense systems utilize metalloenzymes including Se-dependent glutathione peroxidase and Cu and Zn superoxide dismutase. The aim of the present work was to determine the protective effect of two trace elements, Se and Zn, on cultured human diploid fibroblasts exposed to UV-A radiation (broad-spectrum source with a maximum intensity at 375 nm). Selenium in the culture medium (0.1 mg/L) in the form of sodium selenite increased the synthesis and activity of glutathione peroxidase by 60.5% in the absence of exposure to UV-A radiation and by 35% after irradiation with 5 J/cm2 (P = 0.043). The presence of this element significantly increased the survival of UV-A-irradiated fibroblasts (P < 0.0001). This confirms the essential role of Se in the detoxifying activity of the enzyme. In addition, thiobarbituric acid-reacting substances (TBAR), which are lipid peroxidation markers, decreased in the presence of exogenous Se: -19% and -22% without irradiation and after irradiation with 5 J/cm2 (P = 0.056). When Zn was added at the dose of 6.5 mg/L as ZnCl2, fibroblasts subjected to oxidizing stress induced by UV-A were protected from cytotoxicity (P < 0.0001). The TBAR production decreased significantly: -33% without irradiation and -34% after irradiation with 5 J/cm2 (P = 0.008). Superoxide dismutase activity, however, decreased after supplementing with Zn: -26% without irradiation and -20% after UV-A irradiation (P = 0.017). The antioxidant properties of Zn are thus apparently independent of superoxide dismutase activity.

Cell Division↗
PubMed1993

Effect of iron supplementation during pregnancy on trace element (Cu, Se, Zn) concentrations in serum and breast milk from Nigerian women.

Trace element concentrations in serum and breast milk were studied longitudinally in 197 Nigerian women from 6 months of gestation to 6 months postpartum; 99 of them received a daily iron supplement of 100 mg from 6 months of gestation to delivery. During the last 3 months of pregnancy, serum selenium declined, whereas serum zinc remained unchanged and serum copper increased. After delivery, copper concentration in maternal serum decreased, whereas serum zinc increased from delivery to 3 months postpartum and then reached a plateau. Serum selenium increased from delivery to 6 months postpartum. In breast milk, selenium and zinc decreased from 5 days to 6 months postpartum. Copper in breast milk also declined during the course of lactation but reached a plateau by 3 months postpartum. Iron concentration in breast milk remained unchanged during the study. Iron supplementation had no significant effect upon the concentrations of copper, selenium and zinc in mother serum and breast milk. In umbilical serum, iron status, copper and zinc levels were similar in the two groups, whereas, unexpectedly, selenium concentration was significantly decreased (p < 0.03) in the iron-supplemented group. Taken together, our results suggest that the beneficial effect of iron supplementation on iron deficiency was not associated with an adverse effect on copper and zinc status. On the other hand, our results suggest that Nigerian women had a marginal zinc status but an adequate selenium status.

Adolescent↗
PubMed1993

[Trace elements balance in treated phenylketonuria children. Consequences of selenium deficiency on lipid peroxidation].

We studied Ca and Mg and trace elements (Zn, Cu, Fe, Mn, Se) in 15 P.K.U. children treated with strict Phe-reduced diet and in a control group. P.K.U. children are significantly lower (p < 0.01) plasma and erythrocyte Se as well as significantly lower (p < 0.01) activities of Glutathione-Peroxidase (GSH-Px), a seleno-dependent enzyme in erythrocytes and in plasma. Concomitantly with defective GSH-Px activities we observe significantly (p < 0.01) increased levels of lipid peroxidation products: malonaldialdehyde (MDA) and organic hydroperoxides (O.H.P.). So, Se supplementation appears to be necessary in low phenylalanine products used in P.K.U. treatment.

Child↗
PubMed1993

Selenium determination in human milk in Niger: influence of maternal status.

Selenium (Se) was determined in human milk from women residing in Niamey (Niger) at different periods of lactation. To this purpose, a rapid electrothermal atomic absorption spectrometric (EAAS) method using Zeeman background correction and palladium matrix modifier was developed. Linear range (10 nmol/L-6.25 mumol/L, 0.8-494 micrograms/L), within-run (7.6%), between-run (10.4%), precision and recovery of standard addition (101 +/- 7%) were sufficient to allow routine determination of Se in breast milk. Values of breast milk Se decreased from 5 days to 6 months postpartum. No significant correlation was found between the milk Se and any of the following parameters: mother serum Se, parity, age of the mother, age of the previous child. In mother serum, Se concentration increased from delivery to 3 months postpartum and remained stable afterwards. The Se concentrations found in breast milk and in mother serum suggest that Se status is adequate in Niger.

Adolescent↗
PubMed1993

[Tumor necrosis factor (TNF) and oxygen free radicals: potential effects for immunity].

During various biological processes as inflammation or septic shock, free radical damages are produced by a direct production of oxygen radicals by phagocytes, but also by a TNF-mediated generation in target cells. Antioxidants have been demonstrated as protective against TNF cytotoxicity. We try to measure directly the free radical produced by murine recombinant TNF on L929 cells, by detecting the direct light produced by decomposition of superoxide using an adapted chemiluminometer. We measure also the chemiluminescence after addition of luminol. These techniques demonstrate the effective production of oxygen radicals. Unfortunately they have a rather poor specificity and sensitivity. So we use the protective effect of antioxidants on cytotoxicity to investigate the origin of the productive mechanism. We evaluate cytotoxicity of 1 U/ml TNF on L929 murine fibroblasts after 24 hours incubation with actinomycin D by the MTT and Cr51 release. Using the MTT test we observe that addition of thiourea or catalase has the better protecting effect when Zu-Zn SOD had few effect. Reversely using the Cr51 release we observe a good protective effect of Cu-Zn SOD simultaneously with a good protective effect of catalase. So the difference in the effect of various antioxidant agent do not permit to identify the species generated, but depend more on the ability of the antioxidant to reach the cell compartment tested by the method (membrane, or mitochondria). The oxidative effect of TNF is beneficial in physiological condition to destroy cancerous or virus infested cells infested by virus inside the body. But this effect can be deleterious in situation of deficiency in some antioxidant. TNF-induced free radicals can increase the replication of virus as HIV-1 and destroy immunocompetent cells as T cells. This last action explains the defect in cellular immunity observed in oxidative stress and the immunostimulatory effect of many antioxidants.

Animals↗
PubMed1993

Zinc.

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Erythrocytes↗
PubMed1993

Measurement of oxidative base damage to DNA by using HPLC-32P-postlabelling and GC/MS-selective ion monitoring assays.

A 32P-postlabelling assay has been developed for singling out specific oxidized base lesions. Emphasis was placed on the quantitative aspect and the accuracy of the assay, which require the use of calibration curves and microreactions, respectively. The method was successfully applied to the detection and the measurement of adenine N1-oxide and 5-hydroxymethyluracil in cells exposed to agents inducing oxidative stress including H2O2 and UV-A radiation. The sensitivity of the assay allows the detection of one lesion in 10(6) normal bases in 1 microgram of DNA. The GC/MS method when coupled to the selective ion monitoring (SIM) technique is about twenty times less sensitive, even for suitable substrates such as 5-hydroxymethyluracil and 5-hydroxyuracil, than the 32P-postlabelling assay. However, the former assay is much easier to apply, even though a derivatization step is necessary, and provides unambiguous structural information on the compound to be measured. Accurate quantitative measurements can be obtained when stable, isotopically labelled standards are available.

Chromatography, High Pressure Liquid↗
PubMed1993

Zinc deficiency and dietary folate metabolism in pregnant rats.

Five groups of pregnant Wistar rats (zinc-deficient diet without folate supplementation; folinic acid, folate monoglutamate, folate polyglutamate-supplemented groups receiving zinc-deficient diet; pair-fed groups as controls) were fed from day one of fertilization with a semisynthetic zinc-deficient diet containing 0.2 mg/kg of Zn in the diet for the 4 deficient groups and 100 mg/kg for the pair-fed group. After 20 days, the zinc status (plasma, liver, femoral bone) was significantly decreased in the zinc-deficient groups. The liver and plasma folate levels were lower in the zinc-deficient groups compared to the pair-fed group. Moreover, the folinic acid and the polyglutamate folate supplementations (100 mg/kg diet) did not normalize the folate status of the animals. Only the supplementation with folate monoglutamate led to correct folate levels in the pregnant rats. Nevertheless, no form of folate supplementation prevented fetal growth retardation in any of the zinc-deficient groups. These results indicate that zinc deficiency in pregnant rats decreases folate bioavailability of folinic acid, folate polyglutamates and, to a lesser extent, that of folate monoglutamate. However, no form of folate supplementation (i.e., folate monoglutamate) prevents fetal growth defect and the incidence of malformation in zinc-deficient rats.

Animals↗
PubMed1993

Lipid peroxidation and trace element status in diabetic ketotic patients: influence of insulin therapy.

Lipid peroxidation is known to accelerate aging and microvascular lesions in diabetic patients. We studied the acute influence of improved glycemic control on the concentrations of plasma lipid peroxidation intermediates [malondialdehydes (MDA), organic hydroperoxides (OHP)] in ketotic insulin-dependent diabetic patients, as well as the interplay of enzymes such as glutathione peroxidase (GPX) and CuZn superoxide dismutase (CuZn-SOD), and trace elements (Zn, Se, Cu) postulated to be involved in free radical protection. These plasma components were measured on the first day of hospitalization (T0) and when the patient had attained a stable glycemic state after continuous insulin treatment (T1). Plasma MDA and OHP concentrations were high at the beginning of the study but approached reference values after glycemic equilibration. Plasma zinc concentrations were significantly (P < 0.05) decreased during the ketotic state, but also approached reference values with glycemic equilibration. Plasma selenium concentrations and GPX activity were relatively unchanged between T0 and T1. Erythrocyte GPX activity measured at T1 in six patients was below the reference values, whereas CuZn-SOD activity was not affected. Our results show that enhanced lipid peroxidation is associated with decreased zinc plasma concentrations in ketotic patients and underline the beneficial effects of continuous insulin infusion. The mechanisms involved are still unclear but may indicate the importance of extracellular zinc transfer secondary to glycemic disorders.

Adult↗
PubMed1993

Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.

Adolescent↗
PubMed1992

Gas chromatographic-mass spectrometric method for the determination of selenium in biological samples.

The determination of selenium by capillary gas chromatography-mass spectrometry (GC-MS), using an enriched stable isotope 76Se as internal standard, is described. Reference values for selenium in human biological fluids (serum, red blood cells and urine) are reported. With the advent of new compact capillary GC-MS (benchtop) instruments, this method will be very simple and accurate for routine analysis.

Adolescent↗
PubMed1992

High-performance liquid chromatographic separation of malondialdehyde-thiobarbituric acid adduct in biological materials (plasma and human cells) using a commercially available reagent.

The assay of malondialdehyde (MDA) is widely used in clinical chemistry laboratories to investigate lipid peroxidation in oxidative pathologies. In the present work, the thiobarbituric acid (TBA) reaction was carried out on plasma, human erythrocytes and fibroblasts. The reagents used were those of the fluorimetry MDA kit manufactured by Sobioda. We have defined the application of this kit to high-performance liquid chromatography. This adaptation satisfied the criteria of good analytical practice. The detection limit was 2.5 pmol per injection. The retention time of the MDA-TBA2 peak (4.96 +/- 0.07 min) led to excellent resolution of the complex. The within-assay (6-12%) and between-assay (11-12%) precisions were satisfactory. The analytical recovery of MDA after spiking samples of human plasma with tetraethoxypropane standards varied from 70 to 100%. The mean lipoperoxide concentration determined in 32 healthy adults (20-40 years) was 1.04 +/- 0.23 mumol l-1 in plasma. Applied to the erythrocytes of fifteen laboratory workers, the method furnished physiological values of 0.59 +/- 0.21 mumol l-1. Concentrations were significantly higher in chronic renal dialysis patients (4.15 +/- 2.35 mumol l-1. The MDA content of fibroblasts cultured in standard medium was 0.38 +/- 0.04 mumol per g of protein and increased (5.78 +/- 1.38 mumol per g of protein) if the cells were grown in an iron-enriched medium. This accurate high-performance liquid chromatographic method for detection of MDA is the first one which can be applied to plasma, red blood cells and cultured cells. This technique will prevent false positives and should make inter-laboratory comparisons possible.

Adult↗
PubMed1992

Evidence of cytosolic iron release during post-ischaemic reperfusion of isolated rat hearts. Influence on spin-trapping experiments with DMPO.

Previous studies of oxygen-derived free radical generation based on spin-trapping methods have shown a signal formed of six bands (sextet) using electron spin resonance spectrometry (ESR) of coronary effluents collected during post-ischaemic reperfusion of isolated hearts perfused with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The origin of this signal has recently become controversial. In the present study we show that, in the rat, this sextet and cytosolic iron release occur simultaneously, and that this signal can be inhibited by the iron chelator desferrioxamine. It also appears that the iron release is not protein bound, and could therefore have a marked catalytic activity. This may be responsible for the production of an artefactural signal observed as the sextet.

Animals↗
PubMed1992

Selenium, glutathione peroxidase (GSH-Px) and lipid peroxidation products before and after selenium supplementation.

Treated phenylketonuric (PKU) children are at risk of selenium deficiency. We have studied 15 treated PKU children and 30 control children. We observed significantly lower (P less than 0.0005) plasma and erythrocyte selenium, as well as significantly lower (P less than 0.0005) plasma and erythrocyte glutathione peroxidase activities (GSH-Px) in PKU children than in controls. The lipid peroxidation products, evaluated as plasma malondialdehyde (MDA), was higher (P less than 0.0005) in PKU children than in controls. Specific oral sodium selenite supplementation (Selenium: 0.13 mumol/kg/day) resulted in a rapid increase of plasma selenium and GSH-Px activity, and after 10 days and 1 month respectively significant difference is no longer observed between PKU children and controls values. Statistically significant differences in erythrocyte selenium, erythrocyte GSH-Px activity and plasma MDA between PKU and control children disappear after respectively 2 months, 4 months and 6 months of selenium supplementation.

Child↗
PubMed1992

Chemical and biochemical postlabeling methods for singling out specific oxidative DNA lesions.

A survey of the main available chemical and biochemical postlabeling assays for measuring oxidative DNA damage is reported. Two main approaches, radio and fluorescent postlabeling, have been used in order to reach a high level of sensitivity of detection. This is required for the measurement of DNA damage within cells and tissues upon exposure to agents of oxidative stress. Most of the methods are based on liquid chromatographic separation of defined DNA modifications following either acidic hydrolysis or enzymic digestion of DNA. In a subsequent step, the isolated base or sugar damages are either radiolabeled or made fluorescent by chemical or enzymatic reactions. Emphasis is placed on the recently developed high performance liquid chromatographic 32P-postlabeling assay, which allows the specific and sensitive measurement of various base damages including adenine N-1 oxide and 5-hydroxymethyluracil at the level of one modification per 10(7) normal bases in a sample size of 1 microgram of DNA. Examples of application of radioactive postlabeling to the measurement of DNA base damage following exposure of human cells to oxidizing agents including hydrogen peroxide and UVA radiation are provided.

Adenosine Triphosphate↗
PubMed1992

Determination of ultrafiltrable zinc in human milk by electrothermal atomic absorption spectrometry.

Percentages of non-protein-bound zinc in human milk have been reported by different workers, but ultrafiltration and zinc determination in human milk have not been comprehensively examined. However, zinc contamination and zinc membrane binding have been described for the determination of non-protein-bound zinc in serum. In this work, ultrafiltration was studied in terms of zinc contamination and zinc membrane binding. An MPS-1 micropartition system fitted with a YMT membrane was used. Zinc contamination was found to be less than 276 nmol dm-3 and the zinc recovery was 85 +/- 4%. The conditions for electrothermal atomic absorption spectrometry were also studied. The detection limit was found to be 26.4 nmol dm-3 and the upper linear range was 4 mumol dm-3. The precision varied from 3% (within-run) to 17% (between-run). The recovery of standard additions was 95 +/- 7% (n = 30, different human milk ultrafiltrate samples). Physiological values varied from 0.46 to 84 mumol dm-3 (4-56% of zinc in whole human milk). Expressed in mumol dm-3, zinc in human milk ultrafiltrate decreased slightly through the lactation period, whereas expressed as a percentage of the total zinc in milk, zinc in human milk ultrafiltrate remained constant from day 2 to day 69 post partum.

Adult↗