Study of the potential oxidative stress induced by six solvents in the rat brain

The mechanisms of action involved in the neurotoxicity of solvents are poorly understood. In vitro studies have suggested that the effects of some solvents might be due to the formation of reactive oxygen species (ROS). This study assesses hydroxyl radical (OH) generation and measures malondialdehyde (MDA) levels in the cerebral tissue of rats exposed to six solvents (n-hexane, n-octane, toluene, n-butylbenzene, cyclohexane and 1,2,4-trimethylcyclohexane). Three of these solvents have been shown to generate ROS in studies carried out in vitro on granular cell cultures from rat cerebellum. We assessed OH production by quantifying the rate of formation of 3,4-dihydroxybenzoic acid using a trapping agent, 4-hydroxybenzoic acid, infused via the microdialysis probe, into the prefrontal cortex of rats exposed intraperitoneally to the solvents. Extracellular MDA was quantified in microdialysates collected from the prefrontal cortex of rats exposed, 6 h/day for ten days, to 1000 ppm of the solvents (except for n-butylbenzene, generated at 830 ppm) in inhalation chambers. Tissue levels of free and total MDA were measured in different brain structures for rats acutely (intraperitoneal route) and sub-acutely (inhalation) exposed to solvents. None of the six solvents studied increased the production of hydroxyl radicals in the prefrontal cortex after acute administration. Nor did they increase extracellular or tissue levels of MDA after 10 days’ inhalation exposure. On the other hand, a decrease in the concentrations of free MDA in brain structures was observed after acute administration of n-hexane, 1,2,4-trimethylcyclohexane, toluene and n-butylbenzene. Therefore, data of this study carried out in vivo did not confirm observations made in vitro on cell cultures.

► The hydroxyl radical generation and malondialdehyde content were assessed in the brain of rats exposed to six solvents. ► No treatment-related increase in the production of hydroxyl radicals for any of the tested solvents. ► A 10 day inhalation exposure to the six solvents did not increase the extracellular and cerebral levels of malondialdehyde. ► Toluene and n-hexane caused a transient significant decrease in the concentrations of free malondialdehyde in cerebellum. ► In vivo results do not confirm results obtained from previous studies carried out in vitro on rat cerebellar granule cells.