Exposição no ar ao tolueno promove apoptose da linhagem germinativa, alterações neurocomportamentais e dano neuronal em Caenorhabditis elegans

Abstract

Organic solvent is a name for a group of organic chemicals that are widely used in industrial processes. Among these products, gasoline has a variable composition of compounds and solvents, but basically consists of aromatic hydrocarbons. Toluene is one of the organic solvents present in gasoline, which has a high degree of volatility, being absorbed mainly by the pulmonary route and reaches the central nervous system promoting toxic action; however, the specificity of the mechanisms involved is little explored. The present work aimed to evaluate the effect of inhalation exposure to toluene in the alternative model Caenorhabditis elegans, in order to validate the model and elucidate the mechanisms of toxicity of this solvent using the advantages of the animal model. N2 wild-type nematodes and the mutant strains EG1285, LX929 and MD701 were used. Worms in the first or fourth larval stage were exposed to toluene for 24-48 hours in a laboratory-developed closed chamber at concentrations of 450, 850, 1,250 and 1,800 ppm. After 24-48 hours of exposure, the analyses were carried out to evaluate the parameters of lethality, development, reproduction, fertility and neurotoxicity. We observed an increase in mortality, the LC50 being calculated for the volatile exposure 1,340 ppm; we also showed a significant developmental delay as we increased the concentration of exposure to toluene. A significant increase in the apoptotic events in germline cells was evidenced, only at the concentrations of 450 and 850 ppm, which corroborated with the reduction of the reproductive rate caused by toluene. Evaluating neurobehavioral parameters, it was found that toluene promoted a significant decrease in locomotion movements at all concentrations used. To characterize the neurotoxic effect of toluene, we found that at concentrations of 1,250 and 1,800 ppm toluene promoted a reduction in the fluorescence intensity of GABAergic and cholinergic neurons, suggesting neuronal damage. Based on the results obtained, we can conclude that toluene presented a significant toxicity in C. elegans through the induction of apoptosis and neurotoxicity.