RESUMO
Epoxiconazole (EPX) is a world widely used chiral triazole fungicide in the agriculture field. The excessive application of this triazole may cause damage to lizards. However, limited information is known about the toxicokinetics of EPX on lizards. Our study aimed to investigate the enantioselective absorption, distribution, metabolism, and elimination (ADME) of EPX in lizards following low and high dose exposure (10 and 100 mg kg-1 bodyweitht (bw)). The results demonstrated that (+)-EPX was easier absorbed than (-)-EPX in lizard plasma. Both (+)-EPX and (-)-EPX were detected in the liver, gonad, kidney, skin, brain, and intestine, with (+)-EPX preferentially distributed in these tissues. The elimination of (-)-EPX was faster than that of (+)-EPX in lizard liver and kidney in the high dose groups. Chiral conversion was found between EPX enantiomers in lizard skin. Simultaneously, five metabolites including M2, M4, M10, M18 and M19 were detected in lizard liver and kidney after EPX enantiomers exposure. The relative concentrations of M2, M4, and M10 were higher in the liver and kidney of (-)-EPX groups than those produced from (+)-EPX groups. The metabolic enzymes CYP3A4 and SULT1A1 primarily mediated enantioselective metabolism of EPX. The conclusions drawn from this study significantly enhance our understanding of the enantioselective behaviors of chiral triazole fungicides in reptiles, offering essential guidance for assessing the risks associated with different enantiomers of triazole fungicides.
Assuntos
Compostos de Epóxi , Fungicidas Industriais , Lagartos , Triazóis , Animais , Triazóis/química , Triazóis/toxicidade , Triazóis/metabolismo , Lagartos/metabolismo , Fungicidas Industriais/química , Fungicidas Industriais/metabolismo , Compostos de Epóxi/metabolismo , Compostos de Epóxi/química , Estereoisomerismo , Fígado/metabolismo , Rim/metabolismo , Masculino , Distribuição TecidualRESUMO
The neurotoxic effects of neonicotinoids (NEOs) have been widely reported in relation to the poisoning of wild birds, yet the underlying molecular mechanism has remained elusive. This study employed Japanese quails (Coturnix japonica) and primary quail embryonic neurons as in vivo and ex vivo models, respectively, to investigate the neurotoxic effects and mechanism of thiamethoxam (TMX), a representative neonicotinoid insecticide, at environmentally relevant concentrations. Following a 28-day exposure to TMX, metabolomic analysis of quail brain revealed TMX-induced changes in glutamatergic, GABA-ergic, and dopaminergic function. Subsequent ex vivo and in silico experimentation revealed that the activation of nicotinic acetylcholine receptors and calcium signaling, induced by clothianidin (CLO), the primary metabolite of TMX, served as upstream events for the alterations in neurotransmitter synthesis, metabolism, release, and uptake. Our findings propose that the disruption of the central nervous system, caused by environmentally significant concentrations of NEOs, may account for the avian poisoning events induced by NEOs.