Implicações da exposição a uma sobrecarga de ferro em adultos e na prole de Drosophila melanogaster e os efeitos da hesperidina

Abstract

Iron (Fe) is a fundamental nutrient for all living cells, but in excess it can be toxic as it catalyzes the formation of free radicals. Exposure to Fe overload during the embryonic period is also a concern, as it can affect the construction of brain circuits, mainly compromising the biogenic amine systems, being able to alter the physiology, synthesis and signaling of these neurotransmitters. Hesperidin (Hsd) is a citrus flavonoid that has pharmacological properties as an antioxidant and mainly neuroprotective, whereas L-dopa was used in this study as a positive control. The aim of the study was to evaluate whether exposure to Fe overload during the adult and embryonic periods of Drosophila melanogaster is related to neurodegenerative changes in adults and neurodevelopmental changes in the filial generation (F1), as well as the therapeutic effects of Hsd against possible changes neurodegenerative to assess the effect of Fe overload, adult flies were exposed to diets containing treatment for 10 days. The flies were divided into six groups: Control, Hsd (10 μM), L-dopa (1 mM), Fe (1 mM), Fe + Hsd and Fe + L-dopa. Motor changes were evaluated by motor behavior (grooming, aggressiveness and balance) and non-motor memory test through aversive phototaxy and tests that characterize anxiety behaviors in flies, such as cleaning and aggression, in addition to the levels of biogenic amines dopamine (DA) and octopamine (OA). To evaluate the effect of Fe overload during the embryonic period, the flies were exposed to Fe (0.5, 1 and 5 mM) for 10 days of treatment, then the parents were removed and the F1 flies were expected to hatch for further analysis. behavioral and biochemical. Another evaluation addressed in this study was the Fe levels in the diets, head and body of flies (parents and offspring), separated by sex. As a result, in manuscript 1 we observed that Hsd attenuated non-motor alterations, such as memory and anxiety deficits, improved monoaminergic deficits and reduced Fe levels in the head of adult flies. As a result of article 1, we observed that the Fe levels of F1 flies was directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching (5 mM), which may be related to the reduction in cell viability of the ovarian tissue of progenitor flies. F1 flies that were exposed to Fe (1 and 5 mM) showed an increase in locomotor activity (hyperactivity) and a significant increase with a greater number of repetitive and aggressive movements. It was also possible to observe an increase in the levels of biogenic amines DA and 5-HT and an increase in the activity of Tyrosine Hydroxylase (TH) in Fe (1 and 5 mM). These results demonstrated that the behavioral damage induced by exposure to Fe may be associated with an increase in monoaminergic levels. Collectively, our data suggest that Hsd attenuated complications caused by exposure to Fe, decreasing locomotor and neurochemical deficits in adult flies.