Relationship between toxicity and oxidative stress of the nanoencapsulated colchicine in a model of Drosophila melanogaster.

Abstract

Drug repurposing allows searching for new biological targets, especially against emerging diseases such as Covid-19. Drug colchicine (COL) presents recognized anti-inflammatory action, while the nanotechnology purpose therapies with low doses, efficacy, and decrease the drug's side-effects. This study aims to evaluate the effects of COL and colchicine nanocapsules (NCCOL) on survival, LC50, activity locomotor, and oxidative stress parameters, elucidating the toxicity profile in acute and chronic exposure in Drosophila melanogaster. Three-day-old flies were investigated into groups: Control, 0.001, 0.0025, 0.005, and 0.010 mg/mL of COL or NCCOL. The survival rate, open field test, LC50, oxidative stress markers (reactive species (RS) production, thiobarbituric acid reactive substances), antioxidant enzyme activity (catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase), protein thiols, nonprotein thiols, acetylcholinesterase activity, and cell viability were measured. As a result, acute exposure to the COL decreases the number of crosses in the open field and increases CAT activity. NCCOL reduced RS levels, increased lipoperoxidation and SOD activity. Chronic exposure to the COL and NCCOL in high concentrations implied high mortality and enzymatic inhibition of the CAT and AChE, and only the COL caused locomotor damage in the open field test. Thus, NCCOL again reduced the formation of RS while COL increased. In this comparative study, NCCOL was less toxic to the antioxidant system than COL and showed notable involvement of oxidative stress as one of their toxicity mechanisms. Future studies are needed to elucidate all aspects of nanosafety related to the NCCOL.