PROTECTIVE EFFECT OF MELATONIN AGAINST DAMAGE CAUSED BY CRYSTALLINE SILICA IN THE CAENORHABDITIS ELEGANS MODEL

Resumo

INTRODUCTION: Silica is an abundant component of the Earth's crust, present in more than 95% of rocks. Human exposure occurs through inhalation. Respirable SiO2 causes increased oxidative stress through the formation of reactive oxygen species. Due to its antioxidant power, melatonin is a substance with the potential to mitigate the effects caused by the generation of ROS. OBJECTIVE: The objective of this study was to evaluate the potential antioxidant effect of melatonin against the damage caused in the C. elegans model exposed to SiO2. MATERIALS AND METHODS: Nematodes were chronically exposed to 5 concentrations of SiO2 and toxicity endpoints (survival, body length and ROS production) were evaluated. Subsequently, experiments were performed with melatonin as pretreatment (3.125 µg/mL, 10 µg/mL, 50 µg/mL). RESULTS: There was a significant reduction in survival and body length (p<0.0001) in the last two concentrations of nematodes exposed to SiO2. In addition, there was a significant increase in ROS production when compared to the control group (p<0.0001). To evaluate the effects of melatonin, the nematodes were pretreated for 1 hour with 3 concentrations of melatonin and were subsequently exposed to the highest concentration of SiO2 (1.000 µg/mL) chronically. After 48 hours, the survival and body length of the nematodes were evaluated. The survival of the nematodes exposed to pretreatment was higher, demonstrating a significant difference (p<0.005) when compared to the silica group without pretreatment. The same was observed in body length (p < 0.0001). Furthermore, it was found that ROS production decreased significantly (p < 0.05) with the presence of melatonin as pretreatment to silica. To demonstrate the mechanism of action of melatonin in the nematode, we used the CF1553 strain and the TJ353 strain. A significant increase in the expression of the SOD enzyme was observed, as well as a significant nuclear migration of DAF-16 with the increase in the melatonin concentration. CONCLUSION: Melatonin protected the nematode from the damage caused by silica via DAF-16, being a potential antioxidant candidate for evaluating the beneficial effects of these substances in more complex models.