Mecanismos bioquímicos de toxicidade do composto 1-octen-3-ol em machos e fêmeas de Drosophila melanogaster

Abstract

Atmospheric pollutants can affect both outdoor and indoor air quality. Exposure to indoor fungal pollution contributes to the emergence of a set of allergic and inflammatory symptoms, configuring a serious threat to public health. The prevalence of such symptoms between the sexes has been a target of studies, which pointed to different inflammatory response levels in males and females. Fungal volatile organic compounds (VOCs) are among the main pollutants found in damp or water-damaged indoor places. 1-Octen-3-ol (pop. mushroom alcohol) is the most abundant fungal VOC found in these spaces and responsible for the typical musty odor. Exposure to 1-octen-3-ol induces inflammatory markers and episodes of allergic rhinitis and conjunctivitis in the inhabitants of these places. In Drosophila melanogaster, 1-octen-3-ol has revealed neurotoxicity and inflammatory potential. However, the effects of 1-octen-3-ol towards mitochondria, an organelle involved in the development of the inflammatory response, and how this compound acts in different sexes are scarce. D. melanogaster (pop. fruit fly), is a relevant model for the study of human diseases, inflammatory disorders, as well as in the understanding of issues related to sex. The present work aimed to investigate the effects of 1- octen-3-ol on biochemical, inflammatory targets and on mitochondrial morphology and bioenergetic rate in D. melanogaster. Females and males of D. melanogaster were exposed separately to an atmosphere containing 1-octen-3-ol (1, 2.5 and 5 μL/L) for 24 and/or 48 hours. Exposure to 1-octen-3-ol (5 μL/L) for 24 hours was able to induce mortality rate and locomotor impairment. In our results from the female group, we observed that 1-octen-3-ol i): increased the activity of Superoxide dismutase (SOD) and decreased the catalase (CAT) activity; ii) induced an inhibition of complex I and II in the electron transport system, a decrease in the bioenergetic rate and disarrangement in mitochondrial cristae profile; iii) increased activity of caspase 3/7 and ERK phosphorylation; iv) increased gene expression of p38MAPK and JNK, and decreased expression of NF-κB and p53; v) and an increase in nitrite levels. While the group of males exhibited: i) an increase in glutathione-S-transferase (GST) and SOD activities; ii) unchanged caspase 3/7 activity; iii) increase in the generation of reactive oxygen species (ROS) at the lowest concentration, in contrast to a decrease in the highest concentration; iv) and a drop in cell viability and in nitrite levels. These findings point to the mitochondria as a crucial target for the toxicity of 1-octen-3-ol in parallel with activation of pro-inflammatory factors and apoptotic signaling pathway cascade in females. However, in male flies, an increase in ROS generation could be involved with the impairment of mitochondrial activity observed through the decrease in cell viability. Nevertheless, the reasons for such differences remain undefined, and our findings indicate that 1-octen-3-ol can trigger unique responses and modulate different pathways in D. melanogaster of both sexes, which could be related to greater susceptibility seen in males.