Efeito protetor flavonoide hesperidina sobre a toxicidade induzida pela exposição aguda ao ferro em Drosophila melanogaster

Abstract

Flavonoids are natural compounds present in many plant types, are chemically classified as polyphenols and are generally found in their free or glycosylated form. Hesperidin (Hsd) is a citrus flavonoid, found mainly in citrus fruits such as orange and lemon, classified as flavanone glycosidic and has antioxidant, anti-inflammatory, anticancer, antiviral, hypolipidemic properties, among others. Iron (Fe) is a fundamental nutrient for all living cells, but in excess it can be toxic because it causes oxidative damage through the formation of free radicals, such as fenton reaction, which result in phenomena of oxidative stress. Deregulation in the metabolism of Fe is associated with cellular damage and also neurodegenerative diseases such as Parkinson's disease and Alzheimer's. The objective of this study was to evaluate the neuroprotective effect of hesperidin on acute exposure to iron in the form of ferrous sulfate in adult male Drosophila melanogaster. The flies were divided into four groups: 1) control, 2) hesperidin (10 μM), 3) Fe (20 mM) as ferrous sulfate, 4) hesperidin (10 μM) + Fe (20 mM). Flies were concomitantly exposed to Fe and Hsd in the diet on filter paper (dissolved in 1% sucrose) for 48 hours, according to their respective groups. Survival and behaviors (tests such as negative geotag, open field and base / top) and ex vivo acetylcholinesterase (AChE) activity in head and body, cell and mitochondrial viability and determination of dopamine on the head of flies. The activity of catalase (CAT), superoxide dismutase (SOD) and glutathione Stransferase (GST), levels of lipid peroxidation (TBARS), reactive species levels (RS), nonprotein thiol content (NPSH), total thiols and iron levels in the head and body of Drosophila melanogaster were also evaluated. Exposure to Fe significantly increased fly mortality, while survivors had significant locomotor deficits with increased AChE activity. However, dietary supplementation with Hsd caused a significant decrease in mortality, improvement of locomotor activity and restoration of AChE activity in Fe-exposed flies. The metal also caused a decrease in the levels of total and non-protein thiols and in the activity of SOD enzymes , CAT and GST, accompanied with a significant increase in RS and TBARS generation, as well as increase in Fe levels in the head and body and reduction in dopamine levels in the head of the flies exposed to the element. These effects prevented by hesperidin. Hesperidin presented the antioxidant potential and attenuated the effect caused by the acute exposure to Fe in Drosophila melanogaster.