Neurotoxicity induced by toluene: In silico and in vivo evidences of mitochondrial dysfunction and dopaminergic neurodegeneration.
Environ Pollut
; 298: 118856, 2022 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-35033616
ABSTRACT
Toluene is an air pollutant widely used as an organic solvent in industrial production and emitted by fossil fuel combustion, in addition to being used as a drug of abuse. Its toxic effects in the central nervous system have not been well established, and how and which neurons are affected remains unknown. Hence, this study aimed to fill this gap by investigating three central questions 1) How does toluene induce neurotoxicity? 2) Which neurons are affected? And 3) What are the long-term effects induced by airborne exposure to toluene? To this end, a Caenorhabditis elegans model was employed, in which worms at the fourth larval stage were exposed to toluene in the air for 24 h in a vapor chamber to simulate four exposure scenarios. After the concentration-response curve analysis, we chose scenarios 3 (E3 792 ppm) and 4 (E4 1094 ppm) for the following experiments. The assays were performed 1, 48, or 96 h after removal from the exposure environments, and an irreversible reduction in neuron fluorescence and morphologic alterations were observed in different neurons of exposed worms, particularly in the dopaminergic neurons. Moreover, a significant impairment in a dopaminergic-dependent behavior was also associated with negative effects in healthspan endpoints, and we also noted that mitochondria may be involved in toluene-induced neurotoxicity since lower adenosine 5'-triphosphate (ATP) levels and mitochondrial viability were observed. In addition, a reduction of electron transport chain activity was evidenced using ex vivo protocols, which were reinforced by in silico and in vitro analysis, demonstrating toluene action in the mitochondrial complexes. Based on these findings model, it is plausible that toluene neurotoxicity can be initiated by complex I inhibition, triggering a mitochondrial dysfunction that may lead to irreversible dopaminergic neuronal death, thus impairing neurobehavioral signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tolueno
/
Dopamina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Environ Pollut
Asunto de la revista:
SAUDE AMBIENTAL
Año:
2022
Tipo del documento:
Article