Comparison Between Hesperidin, Coumarin, and Deferoxamine Iron Chelation and Antioxidant Activity Against Excessive Iron in the Iron Overloaded Mice

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.

Hesperidin: A Review on Extraction Methods, Stability and Biological Activities

“…The results showed that hesperidin has more potential iron chelation activities compared to deferoxamine, a popular chelator for treatment of chronic iron overload [70]. The antioxidant activity of hesperidin exhibits also by reducing the production of reactive oxygen species and increasing the activities of antioxidant enzymes, catalase and superoxide dismutase [71,72]. It should be mentioned that hesperidin exhibits lower antioxidant activity in comparison to its aglycone form, alike other flavonoids [60].…”

The natural iron chelators' ferulic acid and caffeic acid rescue mice's brains from side effects of iron overload

“…A: negative control group (received normal saline), B: DFO-treated group (25 mg/kg/day DFO as i.p. injection), C: positive control group (iron-overloaded), D: DFO-treated iron-overload group (25 mg/kg/day), E: caffeic acid-treated iron-overloaded group (30 mg/kg/day), F: caffeic acid-treated iron-overload group (50 mg/kg/day), G: ferulic acid-treated iron-overload group (30 mg/kg/day), and H: ferulic acid-treated iron-overloaded group (50 mg/kg/day) (2,19,28,29). The dosage of ferulic acid was selected according to previous studies.…”

“…DFO-treated mice received DFO (25 mg/kg/day; i.p.) four times a week for 4 weeks (2,8). Groups A and B received normal saline in the 3rd month.…”

“…The natural iron chelators' ferulic acid and ca eic acid rescue mice's brains from side e ects of iron overload Introduction Iron is an essential element for the survival of organisms (1,2). The brain needs iron for many important functions, such as myelination, neurotransmitter synthesis, nitric oxide metabolism, and other biochemical activities (3).…”

“…Heavy metal imbalances such as Fe, Cu, and Zn lead to oxidative stress, which is the key to many brain diseases (4,6). For instance, increased levels of these metals are observed in specific areas of the brain in Alzheimer's and Parkinson's disease, and other brain diseases (2,7,8). Brain iron homeostasis is very important and its hippocampal deposition affects memory and learning (3).…”