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Biomedical subjects

L Barret

Publications and source records attributed to L Barret.

At least 19 recordsLinked to original sources
PubMed2005

Chronic consumption of ethanol leads to substantial cell damage in cultured rat astrocytes in conditions promoting acetaldehyde accumulation.

AIMS: This study aimed at comparing the cerebral cytotoxicity of ethanol and its main metabolite acetaldehyde after acute or chronic exposures of rat astrocytes in primary culture. METHODS: Cytotoxicity was evaluated on the cell reduction of viability (MTT reduction test) and on the characterization of DNA damage by single cell gel electrophoresis (or comet assay). RESULTS: Changes in astrocyte survival and in DNA integrity only occurred when the astrocytes were chronically exposed to ethanol (20 mM; 3, 6 or 9 days). On the other hand, viability and DNA integrity were deeply affected by acute exposure to acetaldehyde. Both effects were dependent on the concentration of acetaldehyde. The cytotoxic effect of acetaldehyde was also indirectly evaluated after modifications of the normal ethanol metabolism by the use of different inducers or inhibitors. In presence of ethanol, the concomitant induction of catalase (i.e. by glucose oxidase) and inhibition of aldehyde dehydrogenase (i.e. by methylene blue) led to acetaldehyde accumulation within cells. It was followed by both a reduction in viability and a substantial increase in DNA strand breaks. CONCLUSIONS: These data were thus consistent with a possible predominant role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after AMT could also suggest a possible direct ethanol effect and a role for free radical attacks. These data were thus consistent with a possible predominant role of acetaldehyde during brain ethanol metabolism. On the other hand, the effects observed after AMT could also suggest a possible direct ethanol effect and a role for free radical attacks.

Acetaldehyde↗
PubMed2004

Impact of ethanol and acetaldehyde on DNA and cell viability of cultured neurones.

Ethanol consumption has long been associated with brain damage. However, the mechanism underlying this deleterious effect remains unclear. Among different hypotheses, acetaldehyde is regarded by certain authors as playing a major role in the expression of ethanol toxicity, but there are still some uncertainties about the exact nature of its implication. We therefore tried to characterize the profile of the alterations of neuronal viability and DNA integrity obtained after either a direct exposure to ethanol or to acetaldehyde. Ethanol at concentrations within the range of blood alcohol levels in intoxicated humans (< or = 100 mmol/L) induced DNA alterations without any apparent effect on cell viability. Acetaldehyde (< or = 1000 micromol/L) can also induce DNA alterations but with a different profile of the DNA cellular alterations. The comparison between the distributions of the comet tail DNA indicated that ethanol induced strong breaks (tail DNA > or = 60 a.u.) generation whereas acetaldehyde rather induced lower breaks (20 < or = tail DNA < or = 50 a.u.) formation but affecting a greater number of neurones. Acetaldehyde had thus a different genotoxic potential which may suggest a different mode of action or a different cellular target. Furthermore, when a single 100 mmol/L ethanol exposure did not lead to any loss of cell viability, the addition of an inhibitor of aldehyde dehydrogenase was followed by a significant loss in viability. In contrast, the inhibition of catalase, which suppresses acetaldehyde synthesis, led to no reduced viability in the same exposure conditions. ROS also reduced viability, but this was observed only after both cytochrome P450 stimulation and catalase inhibition. These combined results could suggest that acetaldehyde may play a significant role in the expression of ethanol toxicity in brain.

Acetaldehyde↗
PubMed2004

Ethanol can modify the effects of certain free radical-generating systems on astrocytes.

The central nervous system is vulnerable to oxidative stress, especially when a toxicant can modify the physiological balance between anti- and pro-oxidant mechanisms. Among brain cells, astrocytes seem less vulnerable than neurons, but their impairment can dramatically affect neurons because of their protective role toward neurons. Ethanol is able to stimulate the formation of reactive oxygen species and modify the activity of most of the antioxidant agents. However, ethanol can react with the OH* radical to form the alpha-hydroxyethyl radical, which is considered to be less toxic. Ethanol also can stimulate H2O2 degradation through catalase activation. This study, therefore, sought to determine whether ethanol affected the sensitivity of astrocytes exposed to various free radical-generating systems. The cellular impact of such exposure was assessed by assays exploring cytotoxicity (i.e., NR (neutral red) and MMT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetiazolium bromide) reduction assays) and genotoxicity (comet assay) induced by these treatments. DNA alterations were evaluated by single-cell gel electrophoresis (comet assay), considered a precocious biomarker of intracellular alterations. After concomitant exposure to H2O2 and ethanol, the viability of astrocytes decreased significantly whereas the mean percentage of DNA in the tail increased,reflecting DNA damage (H2O2 was either directly added to the culture medium or endogenously produced from menadione). Ethanol also reduced the loss of viability and DNA alterations after exposure to OH* radicals produced by a Fenton system. The exposure to a xanthine/xanthine oxidase system had the same effect.

Animals↗
PubMed2000

Effects of chronic ethanol exposure on acetaldehyde and free radical production by astrocytes in culture.

In a previous study, the production of acetaldehyde and free radicals derived from ethanol was characterized in astrocytes in primary culture. In the present study, the effects of chronic exposure on the production of both compounds as well as on the main antioxidant system were compared with those of an acute exposure. This was done to better understand the different ways the brain reacts to these modes of exposure. Under these conditions, both a time-dependent increase in the accumulation of acetaldehyde and a decreased formation of the alpha-hydroxyethyl radical were shown. This was associated with increased activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPX) and with decreased glutathione (GSH) content. These effects, which counteract reactive oxygen species (ROS) formation by stimulating the main enzymes of the antioxidant system, were also associated with the reduced amount of radicals derived from ethanol. This could be a beneficial effect, but this was counter-balanced by the increased rate of acetaldehyde accumulation, whose high toxicity is well known. All these effects underline the crucial role played by catalase which, on one hand converts hydrogen peroxide to water and, on the other hand, ethanol to acetaldehyde.

Acetaldehyde↗
PubMed2000

A fatal case of chlorate poisoning: confirmation by ion chromatography of body fluids.

A 49-year-old male chemical industry worker was admitted to intensive care with a 24-hour history of respiratory failure, vomiting, headache, stupor, arterial hypotension, and cyanosed face and limbs. He had acute haemolysis (3.9 g/L plasma haemoglobin concentration) and 30% methaemoglobinaemia. Whereas the search for alcohol, barbiturates and opiates was negative, benzodiazepines and tricyclic antidepressants were present. The patient was in fact being treated with fluvoxamine, amitryptiline, and alprazolam. As the clinical and biological signs suggested chlorate poisoning, chlorate was looked for by using an aniline color reaction. It was found in gastric content and urine. Treatment consisted in mechanical ventilation, vasoactive amines, methylene blue, plasma exchange, exchange transfusion, and haemodialysis. Despite this, the patient had several cardiac arrests and refractory metabolic acidosis. He died 12 h after his admission. Specific ion chromatography was used afterhand to assay the chlorate in various body fluids. The technique was based on a separation on an ion exchange Dionex AS 12A column coupled with conductivity detection. A quantitative estimation was carried out by using external calibration with a four-point calibration curve which was linear between 1 and 15 mg/L. The measured plasma levels of chlorate were 78 and 29 mg/L respectively before and after exchange transfusion. Gastric-lavage liquid contained 1300 mg/L of chlorate and urine 4300 mg/L. Ion chromatography, which is routinely used in environmental studies helped to confirm a massive oral intake of chlorate by measuring the corresponding blood and urine chlorate concentrations, data which had only rarely been reported previously.

Accidents, Occupational↗
PubMed1997

Free radical production after exposure of astrocytes and astrocytic C6 glioma cells to ethanol. Preliminary results.

Formation of the alpha-hydroxyethyl radical (CH3 degree CHOH) has already been extensively demonstrated after ethanol metabolism in the liver. Despite favourable conditions, this formation in the brain has remained speculative since there is no direct experimental evidence in intact brain cells. In this preliminary study, the formation of such a radical was observed after exposure of astrocytes and astrocytic C6 glioma cells to ethanol. These cells were studied because astrocyte integrity is essential for normal growth and functioning of neurons. The free radicals were detected by EPR spectroscopy using the spin trapping technique. Astrocytes appeared to be more sensitive than the C6 cells to free radical formation as the intensity of the signal was higher after exposure of the astrocytes and increased with time, a fact not observed after exposure of the C6 cells.

Animals↗
PubMed1997

Characterization of the production of acetaldehyde by astrocytes in culture after ethanol exposure.

The nervous system is one of the main targets of ethanol toxicity. Astrocytes might play an important role in ethanol-induced brain toxicity, because their integrity is essential for the normal growth and functioning of neurons. On the other hand, acetaldehyde has been implicated as a mediator in some of the biochemical, pharmacological, and behavioral effects of ethanol. The present study aimed at demonstrating the ability of astrocytes in culture to produce acetaldehyde from ethanol. Significant metabolization of ethanol with production of acetaldehyde was demonstrated in the primary culture of astrocytes. This production was quite low, compared with that usually observed in hepatocytes, but was in the same range as that measured in whole brain homogenates and corresponded to biologically active levels. Such a demonstration could bring new elements for understanding of ethanol neurotoxicity.

Acetaldehyde↗
PubMed1996

Characterization of the morphological variations of astrocytes in culture following ethanol exposure.

The nervous system is one of the main targets of ethanol toxicity and it has been suggested that astrocytes might play an important role as their integrity is essential for the normal growth and functioning of neurons. Morphological variations of astrocyte cultures were therefore examined after exposure to various doses of ethanol (0.5, 1 and 2%) for different durations (24, 48, 72 and 96 h). The percentage of cell viability and the cell density were calculated and the changes in astrocyte morphology were assessed by an image analysis system (Samba 2005) allowing the characterization of 5 parameters (perimeter, surface, elongation factor, convexity factor and the form factor) of a great number of cells (over 6500). This was necessary because of the high variability in normal cultured astrocyte morphology. A two-way statistical approach (2-factors ANOVA completed by stepwise discriminant analysis) was adopted to emphasize the differences between control and exposed cells. In such conditions, ethanol treated cells became more elongated, less circular and more concave and did not grow like non-exposed cells. The mean pooled values of these parameters tended to be modified as a function of the dose of ethanol. The relationships between parameters clearly separated the groups as a function of the different doses. Finally no significant difference was observed in cell viability and cell density despite lower scores in the groups exposed to the highest dose of ethanol for the longest time. Our results suggest that ethanol might affect astrocytes in two different but probably complementary ways by modifying the cell shape and by altering normal cell development.

Animals↗
PubMed1992

Cytochrome P-450-dependent hydroxylation in migraine.

The hypothesis was tested that an acute oxidation deficiency related to potential dietary trigger factors plays a role in the migraine attack. Migraine sufferers (14F and 4M), fulfilling the criteria for migraine with and without aura according to the classification of the International Headache Society, were coadministered oral mephenytoin (100 mg) and debrisoquine (10 mg) during the initial phase of a typical migraine attack. This was repeated during a period without migraine. The hydroxylation of mephenytoin and debrisoquine hydroxylation did not differ during and without the migraine attack. We conclude that hydroxylation, via cytochrome P-450 (2D6, 2C8 and 9), is not reduced during the migraine attack. The results do not support the hypothesis that oxidation deficiency is involved in the pathophysiology of migraine.

Chromatography, Gas↗
PubMed1992

Morphometric and biochemical studies in trigeminal nerve of rat after trichloroethylene or dichloroacetylene oral administration.

Trigeminal nerve impairment is one of the main features of the clinical spectrum observed after trichloroethylene (Tce) exposure. A morphometric study of teased fibres, an analysis of the fatty acid composition of total lipids of the trigeminal trunk, measurements of myelin basic protein (MBP) and of 2'-3'-cyclic nucleotide 3' phosphohydrolase (CNP) activity were used to characterize this lesion. Furthermore, the effects of Tce and of dichloroacetylene (Dca), a breakdown product supposed to be the main cause of the trigeminal neuropathy, were compared under the same experimental conditions. Results showed a significant decrease of the internode length and of the mean fibre diameter in the Dca group whereas these values, although also diminished, were not significantly affected in the Tce group. In the trigeminal nerve, this was associated with a significant (46%) decrease in sigma. (n-6) fatty acid and a 22% decrease in sigma. (n-3) fatty acid contents in the Tce group whereas these decreases were respectively 32% in sigma. (n-6) fatty acid and 27% (significant) in sigma. (n-3) fatty acid contents in the Dca group. In this group, a 64% increase in sigma. Fatty aldehydes was also observed. Finally, Tce or Dca had only a slight effect on the overall profile of fatty acid content in the brain and no significant variation was observed in MBP level and CNP activity. Both compounds can thus induce trigeminal nerve alterations, but with a higher intensity for Dca.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1991

A morphometric evaluation of the effects of trichloroethylene and dichloroacetylene on the rat mental nerve. Preliminary results.

Morphometric analysis was used to compare the effects of trichloroethylene (Tri) and dichloroacetylene (Dca) on the fibre parameters of the trigeminal nerve. Treated animals were clearly separated from controls according to a discriminant analysis. Furthermore, in the class of nerve fibres defined by a clustering analysis and corresponding to the largest fibres, myelin thickness was significantly decreased in the Dca group, but less so in the Tri group. In the group of the smallest fibres however, the myelin thickness was significantly increased by the treatments, but especially by Tri. Such a variability in the effects of Tri has already been demonstrated. Mechanisms for this are quite unclear although demyelination could be involved as already suggested. Our results thus show the ability of Tri and Dca to alter nerve parameters but probably with different modes of action depending on the size of the fibre.

Acetylene↗
PubMed1987

Determination of beta-endorphin in alcoholic patients in the acute stage of intoxication: relation with naloxone therapy.

beta-Endorphin was measured in the plasma of control subjects and 12 chronic alcoholics in the acute stage of ethanol intoxication. Naloxone was administered and the level of beta-endorphin was compared before and after treatment. The increased level of beta-endorphin in the intoxicated subjects supports the presence of ethanol interactions with the opioid system, since pituitary secretion does not seem to be involved. Furthermore, the coexistence of high levels of beta-endorphin and an effective naloxone response suggest a possible link between the two.

Adult↗
PubMed1986

[Somatosensory evoked potentials of the trigeminal nerve in chronic trichloroethylene poisoning].

Industrial intoxication by trichloroethylene can produce neurological disturbance of the trigeminal nerve. Therefore, among 105 workers exposed to this toxin, we recorded cortical responses after stimulation of the trigeminal nerve (TSEP) and we compared our results with a control group of 52 subjects. We considered the physical examination exploring, the facial sensitivity and reflexes, the levels of urinary metabolites of trichloroethylene and TSEP. We can describe 4 groups of workers: group A, 13 subjects with perturbations of clinical and evoked responses; group B, 27 subjects with normal physical examination though with disturbed TSEP; group C, 6 subjects had an abnormal examination though evoked responses were normal; group D, 59 subjects had normal clinical examination and TSEP. Disturbed TSEP (particularly delayed responses) are found among the older workers with the longest duration of exposure and higher level of exposure. The alteration of TSEP may appear before clinical disturbance. TSEP could represent a useful test for the supervision of the exposed workers and the clinical diagnosis of the trigeminal impairment.

Adult↗