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 ROS-inducing 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.
Highlights
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 Ca2+ and Ca2+-regulated events [11, 12], and neuronal and astrocytic culture morphology [13]
There was no difference in lipid peroxidation between crude synaptosomes isolated from the cortices of control animals, or those from animals treated with toluene (1 g/kg body weight) for 1 hr
The main purpose of the present study was to characterize the effect oftoluene on lipid peroxidation and on the stimulation of reactive oxygen species formation, both in vivo and in vitro, and to identify what metabolites of toluene may contribute to the neurotoxicity of the solvent
Summary
Several recent studies have centered around the ability of toluene to alter neuronal membrane fluidity [8,9,10,11], levels of intracellular Ca2+ and Ca2+-regulated events [11, 12], and neuronal and astrocytic culture morphology [13] 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. Toluene has been shown to induce lipoperoxidation in pulmonary alveolar macrophages [20], while p-xylene, a structural analogue, caused similar increases in lung microsomes [21] Given these findings, this study was undertaken to determine whether reactive oxygen species and related membrane events play a role in the neurotoxicity that results from toluene exposure
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