Effect of toluene on rat synaptosomal phospholipid methylation and membrane fluidity

LeBel, Carl; Schatz, Robert A.

doi:10.1016/0006-2952(89)90680-1

Cited by 18 publications

(9 citation statements)

References 39 publications

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“…Na + /K + -ATPase activity decreased in malnourished animals and showed a trend to increase with the administration of toluene. Toluene increases the affinity of ATP with its enzyme (19,20) modifying membrane fluidity, which in turn facilitates structure-activity interactions and membrane dynamics (6). On the other hand, total ATPase activity partially increased in all animal groups, both with the normal and with the protein-deficient diet; however, significant differences were only found in animals with regular diet and toluene dose of 1.5 g/kg.…”

Section: Discussionmentioning

confidence: 99%

Effect of Toluene and Nutritional Status on Serotonin, Lipid Peroxidation Levels and NA+/K+-ATPase in Adult Rat Brain

et al. 2005

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The aim was to evaluate the effect of toluene and nutritional status on levels of serotonin (5-HT), 5-hydroxytryptophan (5-HTP), Na+/K+-ATPase, total ATPase and lipid peroxidation (TBARS) in rat brain. Study was conducted with malnourished (MN), well-nourished (WN) and normal Wistar rats. Three groups were formed for each nutritional status: control group I received 0.9% NaCl; toluene (1 g/kg) was administered to group II, and 1.5 g/kg to group III. Levels of 5-HT decreased (P< 0.05) in WN toluene groups, and 5-HTP decreased (P < 0.05) in the WN 1 g toluene and MN 1.5 g toluene groups. TBARS decreased (P < 0.05) in WN toluene groups. A trend to increase in Na+/K+-ATPase was found in WN and MN toluene groups, while total ATPase increased (P < 0.05) in the WN 1.5 g toluene group. The results suggest that high concentrations of toluene in single doses induce significant changes in the serotonergic system and alter membrane fluidity more perceptibly in the brain of adult animals with regular diet than in malnourished animals.

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Section: Discussionmentioning

confidence: 99%

Effect of Toluene and Nutritional Status on Serotonin, Lipid Peroxidation Levels and NA+/K+-ATPase in Adult Rat Brain

et al. 2005

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“…In animal experiments, it has been shown that toluene, an organic solvent, significantly reduces synaptosomal phospholipid methylation (Le Bel and Schatz, 1989). We want to put forward the hypothesis that, after exposure to methyl-consuming environmental agents, a person's methytation capacity declines, thereby increasing the toxic effects of the agents.…”

Section: Tl-mthfr May Help Identify the Impact Of Environmental Factorsmentioning

confidence: 99%

Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis

Regland

Germgård²,

Gottfries

et al. 1997

J. Neural Transmission

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The gene for methylenetetrahydrofolate reductase (MTHFR) has shown polymorphism in the general human population. In its homozygous form, a C677T mutation occurs in more than 5% of the grown-up population and produces a thermolabile variant which reduces the overall enzyme activity to less than 30% of normal. We investigated patients with schizophrenia-like psychosis. If hyperhomocysteinemic, their DNA-genotype for thermolabile C677T mutation was determined. Seven of 11 patients, six males and one female, were homozygous for thermolabile MTHFR. One male patient was heterozygous and all three normal homozygotes were females. In the patients who were homozygous for the C677T mutation, the homocysteine concentrations did not respond to vitamin B12 but were normalized by folate supplementation. In the normal homozygotes, however, the homocysteine concentrations were reduced by vitamin B12 alone. Our results suggest that homozygosity for thermolabile MTHFR is a risk factor for schizophrenia-like psychosis. Possibly, this risk may be reduced by folate supplementation.

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“…The rationale for the doses and time-course used was based on previous studies that demonstrated maximal 879 c. J. MATTIA, c. P. LEBEL ands. C. BONDY cerebral levels of toluene within the brain, concurrent with pronounced sedative effects under these conditions [8][9][10]. Metyrapone (200 mg/kg, i.p., 4 mL/kg) was also dissolved in corn oil and given 1 hr prior to toluene.…”

Section: Animals and Treatmentmentioning

confidence: 99%

“…From a mechanistic viewpoint, several recent studies have centered around the ability of toluene to alter neuronal membrane fluidity [8][9][10][11], levels of intracellular Ca 2 + and Ca 2 + -regulated events [11,12], and neuronal and astrocytic culture morphology [13]. Although it is unclear which of these events is causal to the neurotoxicity of toluene, these studies provide strong evidence to suggest that membraneassociated phenomena are integral to the mechanism of action of this solvent.…”

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confidence: 99%

Effects of toluene and its metabolites on cerebral reactive oxygen species generation

Mattia

LeBel

Bondy

1991

Biochemical Pharmacology

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Abstract-The effects of toluene on lipid peroxidation and rates of reactive oxygen species (ROS) formation have been studied in isolated systems and in vivo. The induction of reactive oxygen species was assayed using the probe 2' ,7'-dichlorofluorescin diacetate (DCFH-DA). Toluene exposure (1 g/kg, 1 hr, i.p.) did not stimulate cortical lipid peroxidation as evaluated by measurement of conjugated dienes. Exposure to toluene, however, both in vivo and in vitro, caused a significant elevation of ROS formation within cortical crude synaptosomal fractions (P2) and microsomal fractions (P3). The ROSinducing properties of toluene were blocked in vivo in the presence of a mixed-function oxidase inhibitor, metyrapone. This suggested that a metabolite of toluene may catalyze reactive oxygen formation. Both benzyl alcohol and benzoic acid, in vitro, were found to have free radical quenching properties, while benzaldehyde exhibited significant induction of ROS generation. It appears that benzaldehyde is the metabolite responsible for the effect of toluene in accelerating reactive oxygen production within the nervous system. Benzaldehyde may also contribute to the overall neurotoxicity of toluene.

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Effect of toluene on rat synaptosomal phospholipid methylation and membrane fluidity

Cited by 18 publications

References 39 publications

Effect of Toluene and Nutritional Status on Serotonin, Lipid Peroxidation Levels and NA+/K+-ATPase in Adult Rat Brain

Effect of Toluene and Nutritional Status on Serotonin, Lipid Peroxidation Levels and NA+/K+-ATPase in Adult Rat Brain

Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis

Effects of toluene and its metabolites on cerebral reactive oxygen species generation

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