Hesperidin attenuates iron-induced oxidative damage and dopamine depletion in Drosophila melanogaster model of Parkinson's disease

Abstract

This study has evaluated the action of flavonoid hesperidin on the neurotoxic effects caused by the intake of iron (Fe) in Drosophila melanogaster. Male adult flies, aged 1-3 days, have been divided into four groups of 50 each: (1) control, (2) Hsd 10 μM, (3) Fe 20 mM (4) Hsd 10 μM + Fe 20 mM. During the exposure protocol, the flies have been exposed to a diet containing Hsd and/or Fe for 48 h. The survival and behavioral analyses have been carried out in vivo, and ex vivo. The analyses involved acetylcholinesterase (AChE) activity and Fe levels in the flies' heads and bodies and determination of dopaminergic levels, cellular and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), thiobarbituric acid reactive substances (TBARS) and contents of total thiols and non-proteic thiols (NPSH) in the flies' heads. A significant negative correlation between Fe levels in the head of the flies and the survival, dopamine levels and antioxidant enzymes in the head of the flies has been found. Additionally, significant positive correlation between Fe levels in the head of the flies with negative geotaxis RS and AChE activity in the head of the flies has been found. It demonstrates that the flies which had higher levels of Fe in their heads have demonstrated more susceptibility to neurotoxicity. An important result from our study is that Hsd treatment promotes a decrease in Fe concentration in the head, restores dopamine levels and cholinergic activity of the flies and improves motor function caused by Fe. Hsd also ameliorates Fe induced mortality, oxidative stress and mitochondrial dysfunction. Our results have demonstrated the neuroprotective effect of Hsd and it suggests that flavonoid acts in different ways to protect against the Parkinson disease caused by Fe exposure such as the direct scavenging of RS and activation of antioxidant enzymes.

Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

“…The blood-brain barrier regulates iron entry into the brain (Mehta et al, 2009 ), but we still do not know how iron traffics in the peripheral and central nervous systems or how Fe-S and/or Moco enzymes affect the circadian clock. Answers to questions of the basic cell biology of metal homeostasis are prerequisite for proposing better therapeutics when neuronal functions are compromised in disease (Zhu et al, 2014 ; Calap-Quintana et al, 2017 ; Ruland et al, 2017 ; Poetini et al, 2018 ).…”

Hesperidin modulates the rhythmic proteomic profiling in Drosophila melanogaster under oxidative stress

“…Hesperidin on the other hand, display antioxidative properties by scavenging of free radicals (Garg et al, 2001), restrain free radical synthesis and the distribution of free radical reactions through the chelation of metal (iron and copper) ions (Andjelković et al, 2006), suppresses the superoxide‐derived Fenton reaction (Mladenka et al, 2011) and augment endogenous antioxidative defense system (Poetini et al, 2018). Previous studies had indicated that treatment with flavonoids could reverse the disturbed rhythmicity of antioxidants and biochemical indices (Subramanian et al, 2017).…”

The pro-oxidant effect of dextran sodium sulphate on oxidative stress biomarkers and antioxidant enzymes in Drososphila melanogaster

“…Thus by taking the sample blank reading, the level of interference is taken into consideration and brought to level zero before other readings are determined (Ingle and Crouch, 1988). Some researchers have determined both the level of malondialdehyde produced from lipid peroxidation (Ohkawa et al, 1979), a standard oxidative damage indicator and level of reactive oxygen species via oxidation of fluorescent dye 2,7-dichlorofluorescein diacetate (DCF-DA) a general index of ROS levels (Pérez-Severiao et al, 2004) using the Harwich strain of D. melanogaster (Paula et al, 2016;Saraiva et al, 2018;Poetini et al, 2018). This is supported by our findings from Table 1, in which the inhibition of GST activity may be due to the increase in the toxicity effect of 1.0% DSS.…”