Reduction of iron toxicity in the heart of iron-overloaded mice with natural compounds

Alikhani, Mehrdad; Aalikhani, Mahdi; Khalili, Masoumeh

doi:10.1016/j.ejphar.2022.174981

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…FA and CaA increased CAT activity in the brain, liver, and serum of the treatment mice (Figures 6A-C). Previous studies have shown that the antioxidant enzyme activity was affected by iron overload; and natural products and DFO increased the antioxidant enzyme activity (2,40,41).…”

Section: Discussionmentioning

confidence: 93%

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

2022

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Studies have shown that iron accumulation in the brain leads to neurogenic disorders. Novel iron chelating agents such as natural remedies are useful to decrease the side effects of iron in the brain. In addition, flavones and polyphenols are capable of chelating metals. In the current study, we evaluated the iron chelating capacity of ferulic acid and caffeic acid in the brain tissues of iron-overloaded mice. The mice received iron dextran intraperitoneally four times a week for 6 weeks. Next, blood samples were taken from the mice. In addition, brain tissues were excised for tissue staining as well as total iron and catalase (CAT) activity assessment. Ferulic acid and caffeic acid significantly decreased iron content in both brain and serum samples. Ferulic acid decreased iron by 50 and 51% more than the iron dextran-treated mice and by 43 and 2% more than desferal (DFO)-treated mice in serum and brain, respectively. In addition, caffeic acid reduced iron 57% more than the iron-treated group and 49 and 2% more than the desferal-treated group in the serum and brain, respectively. The catalase activity decreased with the increase in iron. By administering natural compounds, the catalase activity was increased equal to that of the control group. Thus, ferulic acid and caffeic acid might be possible natural iron chelators for brain iron overload therapy.

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Section: Discussionmentioning

confidence: 93%

“…Due to the negative effects of DFO, the use of natural compounds as iron chelators is justified. Other studies have shown some natural products, such as CaA, FA, Berberine, and Vanillic acid, reduced iron content in the heart or liver significantly (2,(40)(41)(42). Resveratrol reduces oxidative stress in the brains of treated rats (43).…”

Section: Discussionmentioning

confidence: 94%

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

2022

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“…The rats in the rutin group (U) were orallyadministered 50 mg/kg rutin three times a week for three weeks [ 21 ]. Rats in the radiation + iron group (RF) received intraperitoneal iron injection five times a week for four weeks after receiving a single 5 Gy dose of gamma radiation [ 22 ]. Rats in the radiation + iron + hesperidin group (RFH) were received radiation and iron as the RF group and hesperidin as the H group.…”

Section: Methodsmentioning

confidence: 99%

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin

Ahmed,

El-Maghraby,

Rashad

et al. 2024

BMC Pharmacol Toxicol

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Background Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis. Methods Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100 mg/kg; four times a week for four weeks; group U received rutin at a dose of 50 mg/kg; three times a week for three weeks; group RF received a single dose (5 Gy) of gamma radiation followed by iron at a dose of 100 mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination. Results In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB. Conclusions In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.

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A whole-body mechanistic physiologically-based pharmacokinetic modeling of intravenous iron

Fan,

Cao,

Wong

et al. 2024

Drug Deliv. and Transl. Res.

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Iron is essential for every cell of the mammalian organism. Iron deficiency is a major public health issue worldwide. Intravenous (IV) iron therapy has been used to treat anemia. However, IV iron therapy is known far away from ideal because the quantitative relationship between the pharmacokinetics and biodistribution of IV iron under different iron statuses remains unclear. Patients are known to suffer adverse effects from excessive iron accumulation. Our objective was to develop a physiologically based pharmacokinetic (PBPK) model of iron in mice and validate its application for predicting iron disposition in rats and humans. Previously published data on iron were collected for constructing the PBPK model of iron in mice, and then extrapolated to rats and humans based on physiologically and chemically specific parameters relevant to each species. The PBPK model characterized the distribution of iron in mice successfully. The model based on extrapolation to rats accurately simulated the ferric carboxymaltose (FCM) PK profiles in rat tissues. Similarly, the observed and simulated serum PK of FCM in humans were in reasonable agreement. This mechanistic whole-body PBPK model is useful for understanding and predicting iron effects on different species. It also establishes a foundation for future research that incorporates iron kinetics and biodistribution, along with related clinical experiments. This approach could lead to the development of effective and personalized iron deficiency anemia treatments. Graphical Abstract Major components and processes of whole-body systemic iron trafficking.

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Reduction of iron toxicity in the heart of iron-overloaded mice with natural compounds

Cited by 7 publications

References 36 publications

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

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

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin

A whole-body mechanistic physiologically-based pharmacokinetic modeling of intravenous iron

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