Biomedical subjects

A Favier

Publications and source records attributed to A Favier.

224 records · Page 13Linked to original sources

PubMedDate not supplied

Modulation by selenium supplementation of lipid peroxidation induced by chronic administration of adriamycin in rats.

Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is accompanied by cardiotoxicity. Previous results suggested that free radical formation may contribute to Adriamycin toxicity. Adriamycin-induced cardiotoxicity was examined in rats maintained on either standard or selenium-supplemented diets. Adriamycin was administered intraperitoneally; the cumulative dose was 15 mg/kg body weight. Selenium status, glutathione peroxidase activities, vitamin E, and MDA contents were determined on red blood cell (RBC) and cardiac homogenates. RBC selenium levels and selenium glutathione peroxidase activity were significantly increased in selenium-supplemented animals compared with control or placebo groups. However, Adriamycin-treated rats showed a significant decrease in RBC selenium and selenium glutathione peroxidase compared with the placebo group. Moreover, treatment with Adriamycin increased RBC MDA content, which was attenuated by the selenium supplementation. In parallel, RBC vitamin E decreased markedly in the Adriamycin-treated group and was totally restored by selenium supplementation. Cardiac biochemical analyses confirmed the blood results. Thus, a free radical mechanism does contribute to Adriamycin cardiotoxicity, and shows the importance of balancing selenium levels in Adriamycin-treated subjects to limit Adriamycin's action. A decrease in Adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would considerably improve the therapeutic benefit of the drug.

Animals↗

PubMedDate not supplied

Oral selenium supplementation in rats reduces cardiac toxicity of adriamycin during ischemia and reperfusion.

The aim of the present study was to assess whether an 8-wk oral selenium supplementation (standard food enriched with 2500 micrograms Se/kg) in rats might prevent the cardiotoxicity of adriamycin (ADR) treatment. ADR was administered at a dose of 2.5 mg/kg body wt intraperitoneally twice weekly for 3 wk. One week after the end of ADR treatment, rats (n = 10 per group) were killed and their hearts were perfused on a Langendorff mode and subjected to a 30-min period of low-flow ischemia (residual flow = 0.1 ml/min) followed by reperfusion (15 min). The results were as follows: 1) selenium supplementation significantly increased the activity of cardiac mitochondrial glutathione peroxidase (GPx) in ADR-treated rats (control: 206 +/- 17.4 IU/g protein; Se: 277 +/- 24.5 IU/g protein, p < 0.05); 2) selenium supplementation reduced myocardial malondialdehyde content in ADR-treated rats (control: 1220 +/- 49.1 nmol/g protein; Se: 1010 +/- 75.9 nmol/g protein; p < 0.05); and 3) ADR treatment significantly increased the degree of reperfusion-induced structural alterations to sarcomeres compared to untreated hearts. Again, this phenomenon was abolished by selenium supplementation. In conclusion, this study demonstrates that selenium supplementation is able to limit ADR cardiotoxicity in isolated rat hearts submitted to a sequence of ischemia/reperfusion.

Animals↗

PubMedDate not supplied

Beta-carotene enhances natural killer cell activity in athymic mice.

To study the effects of beta-carotene on Natural Killer (NK) cells, we chose athymic mice whose spleens have a higher percentage of NK cells than conventional mice. Preliminary studies conducted with beta-carotene given intraperitoneally to athymic mice xenografted with a small-cell lung carcinoma resulted in a slight but significant antiproliferative effect (unpublished observations). We speculated that such an activity of beta-carotene was related to its immunostimulating properties. NK cell activity in ungrafted athymic mice as influenced by beta-carotene was studied. Mice received beta-carotene intraperitoneally. Splenic NK cells were labelled with monoclonal antibody and numeration was completed by measurement of their functional activity against YAC-1 malignant cells with a 51Cr release assay. In addition, splenic lymphocytes were evaluated for their reduced glutathione (GSH) content. There was a non-significant increase in the number of NK cells in the spleen, however their killing capacity was significantly (p < 0.01) enhanced after beta-carotene treatment. Also the GSH content of splenic lymphocytes was significantly higher in beta-carotene treated mice. Comparison of the average body weights of treated animals and of their respective controls showed that treatment had no adverse effects.

Animals↗

PubMedDate not supplied

[Oxidative stress: value of its demonstration in medical biology and problems posed by the choice of a marker].

Free radical stress results from a desequilibrium in the prooxidant/antioxidant balance. Such a desequilibrium originates in nutritional deficiencies, in inflammatory or stress processes or from environmental exposure. Our body can adapt itself to a moderate range of free radical production but genetic variations can alter such adaptation. Oxidative stress is often partly or totally a cause of various diseases as cancer, atheroma, cataract. But a great number of other diseases as diabetes, infectious processes such as AIDS creates a secondary free radical overproduction that worsens the evolution of the diseases. Monitoring free radical status becomes an interesting challenge for clinical chemists. It can be done by measuring the production of free radicals by patients, as well as their antioxidant capacity, or more often the damages resulting of the stress. Direct determination of free radicals can be obtained by physical methods such as electron spin resonance (ESR) or chemilumisnescence. Chemical trapping seems a good way of investigation by measuring the elimination of specific derivatives of salicylate hydroxylation or nitrosylation. Antioxidant capacity of the subject can be estimated by measuring the status of each antioxidant or by measuring the general antioxidant capacity of plasma or erythrocytes. Generally the evaluation of oxidative stress is performed by the determination of damaged biological products. A number of lipid derivatives can be measured: conjugated dienes, hydroperoxydes, aldehydes (malonaldehyde or hydroxynonenal), hydrocarbides (ethane or pentane in breath). The most controversial but the most used indicator is the determination of malonaldehyde. Other oxidized biological compounds can be measured: derivatives of DNA in urine, oxidized proteins as carbonyl or thiol groups. Oxidized antioxidants can be evaluated in biological fluids to prove the existence of an oxidative stress such as the ratio of oxidized glutathione to total glutathione. Whatever the parameter, its determination needs a lot of care in sampling and assay. Real standardization and quality control are actually lacking.

Antioxidants↗

PubMedDate not supplied

[Glutathione peroxidases: value of their determination in clinical biology].

The role of glutathione peroxidase in the oxidative metabolism and recent advances in the demonstration of the consequences of the desequilibrium in the proxidant/antioxidant balance on biological molecules oxidation, intracellular signals transduction, apoptosis and necrosis, have led to new approach in the knowledge of many pathological processes. Methods for determining antioxidant capacity have been developed. The measurement of glutathione peroxidase activity is a key step in the study of oxidative stress. Its determination in clinical biology needs optimal conditions for standardised assays which will be used for epidemiological studies aimed to evaluate the role of nutritional factors involved in the pathogeny of diseases caused or accompanied by oxidative stress.

Adolescent↗

PubMedDate not supplied

Modulation of natural killer cell functional activity in athymic mice by beta-carotene, oestrone and their association.

In athymic mice, Natural Killer (NK) cells influence the take rate and growth of human malignant tissue xenografts. To confirm preliminary results, comparative experiments were conducted to study the effects of beta-carotene, oestrone and their association on the cytolysis mediated by spleen NK cells from athymic mice receiving these different treatments. Target cells consisted of YAC-1 malignant cells. With a 65% increase of cytolysis (ratio effector/target 50:1), beta-carotene induced a significant activation of NK cells (p < 0.002). This effect could be attributed to its antioxidant properties and confirmed by a moderate increase in erythrocyte glutathione peroxidase activity. On the contrary, oestrone resulted in a significant decrease of cytolysis (p < 0.001). In this case, the prooxidant properties of oestrone could explain its effect on NK cells and agree with the increase of intracellular reduced glutathione level observed. When mice received the combination beta-carotene-oestrone, their opposite effects on NK cell activity were counterbalanced, leading to a moderate change of cytolysis.

Animals↗

PubMedDate not supplied

In vitro comparative study of cytolysis mediated by natural killer cells towards malignant cells preincubated with antioxidants.

We have previously reported that antioxidants such as beta-carotene, were able to enhance cytolytic activity of NK cells. The aim of the present study was to investigate whether preincubating YAC-1 tumor cells in culture with different antioxidants, affected their NK cell-mediated cytolysis. The antioxidants studied were enzymes (superoxide dismutase and catalase), hydroxyl radical scavengers (thiourea, mannitol, dimethyl sulfoxide) and a singlet oxygen quencher: beta-carotene. After 24 hours coincubation with the antioxidants, radiolabeled YAC-1 cells were submitted to the cytotoxic activity of NK cells for a 4 hour period. For some antioxidants, a moderate increase of cytotoxic potential occurred for weak NK cell number. By contrast, a clear decrease of cytotoxic potential was induced with high NK cell number. An antioxidant, with a protective effect which appeared stronger was thiourea, which induced 20, 58 and 36% decrease of cytolysis in the effector-target ratios 50:1, 100:1 and 200:1 respectively. These studies suggest that the malignant YAC-1 cells are vulnerable to treatment by different antioxidants.

Animals↗

PubMedDate not supplied

Comparative distribution of beta-carotene and lycopene after intraperitoneal administration in mice.

To determine the kinetics of accumulation of beta-carotene and lycopene, and their main storage sites, they were separately administered in OFI mice at a single dose of 10 mg/kg body weight or in combination. Animals were sacrificed at given time intervals after intraperitoneal administration and carotenoids were dosed in serum, liver, spleen, kidneys and lungs. A single injection of beta-carotene led to a serum peak at t = 2 h and high levels were detected in the liver after 0.75 hours and in the spleen after 5 hours, with peak values of 10.46 +/- 0.62 and 134 +/- 6 micrograms/g tissue respectively. In contrast, lungs and kidneys did not appear as main accumulation sites. After administration of the carotenoid association, beta-carotene distribution in the four organs was strongly inhibited by lycopene. Concerning lycopene distribution, the concentration values were lower than beta-carotene, the spleen and liver remaining the main storage sites. After administration of a combined dose carotene/lycopene, the percentage of lycopene distribution inhibition was lower compared to the beta-carotene distribution inhibition induced by lycopene. This unusual and non-physiological way of administration for micronutrients leads to high levels of beta-carotene and lycopene in the liver and spleen, and seems of interest in the experimental study and understanding of the biomolecular mechanisms of their activities when administered alone or together.

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