Abstract

ObjectiveIron accumulation in the brain leads to the development of Alzheimer’s and Parkinson’s diseases. Nowadays, iron chelation therapy is the best way to decrease the side effects of iron and amyloid plaques accumulation. Iron chelators are commonly used for the treatment of Alzheimer’s disease. Previous studies have shown that natural products such as phenol and flavonoid compounds could chelate heavy metals. In the current study, we examined the iron chelation activity of hesperidin and coumarin on the brain tissue of iron-overloaded mice.Methods48 NMRI male mice were divided into eight groups (n = 6). Six groups were treated with iron dextran (100 mg/kg/day) four times a week for 6 weeks. After stopping the injections for a month, five groups of iron-overloaded mice were treated with hesperidin, coumarin, and desferal four times a week subsequent for four subsequent weeks. Finally, the mice were anesthetized, and blood samples were collected from the ventricle of the heart for subsequent examination. The brain tissues were isolated and fixed in the 4% paraformaldehyde solution for Perl’s staining.ResultsThe results show that hesperidin and coumarin could strongly chelate excessive iron from the serum and deposit iron from the brain tissue compared to desferal group. Catalase and super oxidase activity were decreased in the iron-overloaded group, but in the treated group by hesperidin and coumarin, the enzyme’s activity was increased significantly.ConclusionHesperidin and coumarin, as natural products, are powerful options to chelate iron ions and increase the activity of antioxidant enzymes.

Highlights

  • MATERIALS AND METHODSIron is one of the most important transition metals in the living system, which is necessary for metabolism

  • The results show that hesperidin and coumarin could strongly chelate excessive iron from the serum and deposit iron from the brain tissue compared to desferal group

  • Catalase and super oxidase activity were decreased in the ironoverloaded group, but in the treated group by hesperidin and coumarin, the enzyme’s activity was increased significantly

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Summary

Introduction

Iron is one of the most important transition metals in the living system, which is necessary for metabolism. It works in redox-active enzymes and oxygen transportation (Baccan et al, 2012). The accumulation of excessive Fe cation generates oxidative stress Some peptides such as ferritin, heme protein, and transferrin stabilize iron in its trivalent state. This protects from the production and generation of harmful reactive oxygen species (ROS) such as superoxide anion (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH). Iron overload leads to Fenton reaction and Haber–Weiss reactions, which cause numerous damages to proteins, membranes, and DNA (Piloni et al, 2013; Khalili et al, 2015a). Naringin, as a natural product and an iron chelation agent, could chelate iron from the brain and serum of the iron-overloaded mice (Jahanshahi et al, 2021)

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