The high affinity of small-molecule antioxidants for hemoglobin

Pușcaș, Cristina; Radu, L.; Carrascoza, Francisco; Moţ, Augustin C.; Amariei, Diana; Lungu, Oana I.; Scurtu, Florina; Podea, Paula; Septelean, Raluca; Matei, Alina; Mic, Mihaela; Attia, Amr A. A.; Silaghi‐Dumitrescu, Radu

doi:10.1016/j.freeradbiomed.2018.06.019

Cited by 19 publications

(27 citation statements)

References 42 publications

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“…Hemoglobin's porphyrin ring holds a central iron atom in the Fe(II) state, however, the part of ferrous‐oxy hemoglobin was oxidized to Fe(III), which explains the existence of a small amount of Fe(III) in Table 1 (Cristina et al., 2018). The ferritin subunit had iron ion binding sites, which could absorb the ferrous iron ions.…”

Section: Discussionmentioning

confidence: 99%

Determination of the iron bioavailability, conformation, and rheology of iron‐binding proteins from Tegillarca granosa

Zhan

et al. 2020

J. Food Biochem.

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Iron deficiency is one of the most common nutrient deficiencies. It can lead to anemia and related dysfunctions and it's estimated that worldwide, nearly 30% of the population who are iron deficient will also have anemia (Dickson et al., 2019; Kedir et al., 2019). Iron deficiency is usually prevented and treated with iron supplementation, which has a number of associated side effects. For example, an excess amount of residual iron with low bioavailability can promote the growth of intestinal pathogens, causing the hepatic inflammation (Koji et al., 2018). About 10% of our daily iron needs normally come from our diet (Zhang et al., 2018) and there has been an increased scientific interest in identifying iron-rich foods and examining iron bioavailability with the aim of helping supplement iron levels through diet. Tegillarca granosa (T. granosa), also known as the blood clam, is an important commercial marine bivalve widely distributed along the coasts of the Indo-Pacific region (Jin et al., 2011). Although T. granosa is rich in heme iron and has been described as a high-quality food source of iron, the quantity, type, and bioavailability of the iron in T. granosa has not been fully investigated. While iron can exist in the iron-binding proteins (IBPs) hemoglobin and ferritin (Sun & Guo, 2012).

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Section: Discussionmentioning

confidence: 99%

Determination of the iron bioavailability, conformation, and rheology of iron‐binding proteins from Tegillarca granosa

Zhan

et al. 2020

J. Food Biochem.

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“…In this case, a Soret band decrease was seen for the 10 mM sample only at 24 h, while the 600−800 nm increases were smaller but still detectable in the 10 mM sample, even at four hours. Plasma antioxidants, such as urate and albumin [7,15,21,39], are indeed expected to additionally protect erythrocytes from stress induced by excess ascorbate. Figure 2.…”

Section: Resultsmentioning

confidence: 99%

“…At physiological concentrations (e.g., 50-150 µM in blood) ascorbate is a frontline defense molecule against oxidative stress, with hemoglobin (Hb) being a key beneficiary, and is also an essential contributor to other molecular mechanisms, such as those related to transition-metal-dependent hydroxylases [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, at much larger concentrations (1 mM and beyond, which is a range occasionally tested in intravenous administration [2]), ascorbate was shown to accelerate the autooxidation of hemoglobin [21].…”

Section: Introductionmentioning

confidence: 99%

Excess Ascorbate is a Chemical Stress Agent against Proteins and Cells

et al. 2020

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Excess ascorbate (as expected in intravenous treatment proposed for COVID-19 management, for example) oxidizes and/or degrades hemoglobin and albumin, as evidenced by UV-vis spectroscopy, gel electrophoresis, and mass spectrometry. It also degrades hemoglobin in intact blood or in isolated erythrocytes. The survival rates and metabolic activities of several leukocyte subsets implicated in the antiviral cellular immune response are also affected. Excess ascorbate is thus an unselective biological stress agent.

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“…It has been reported that N‐terminal amino acid, valine has a significant role in physiologically relevant allosteric behavior with anionic eﬀectors [28a] . Here, Val is present in one of the binding sites of the highest binding conformation of DOX and WF‐a drug, which indicates that the drug may bind to the site previously fixed for an anionic effector.…”

Section: Molecular Dockingmentioning

confidence: 96%

“…The Tyr140 is present in the four highest docked sites; although it′s not reported yet, Tyr140 may play a role in electron‐transfer, albeit to a small extent. It′s also possible that Trp37, a redox amino acid and is present in one of the binding sites, has a role in small electron transfer in 5‐FU [28a] . The general absence of redox‐active amino acids at the binding sites may be correlated with the lack of redox reactivity of 5‐FU toward Hb, as observed in electrochemical studies.…”

Section: Molecular Dockingmentioning

confidence: 99%

Study of Anticancer Drugs Interaction with Hemoglobin by Electrochemical Methods and Molecular Docking: Implications towards Anticancer Treatment

2021

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Chemotherapeutic drugs tend to cause hemolysis; however, hemoglobin's mode of action is still less explored. In the present study, we used electrochemical methods and molecular docking approach to study anticancer drugs and hemoglobin interaction. For this purpose, we prepared self-assembled monolayers (SAMs) of thiolated hemoglobin on the gold substrate. Electrochemically active chemo drugs, i. e., doxorubicin, withaferin-a, and 5-fluorouracil, are selected and allowed to interact with SAMs of hemoglobin at the physiological condition to study the redox activity and impedimetric behavior. Doxorubicin and withaferin-a show similar behavior in cyclic voltammetry and impedance spectroscopic, i. e., redox process due to hydroquinone/quinone/ketone ring, and faster interfacial electro-transfer kinetics and decreasing in electrontransfer resistance with increasing concentration. In contrast, 5fluorouracil shows only the oxidation reaction. The molecular docking studies were in good agreement with the electrochemical study. All selected anticancer drugs are found to bind hemoglobin, with doxorubicin showing maximum binding efficiency and 5-fluorouracil showing the least. Doxorubicin's highest binding sites contain Tyr 145, which may be involved in the electron transport pathway between doxorubicin and hemoglobin, while Tyr35 in withaferin-a, but absent in case of 5-fluorouracil.

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The high affinity of small-molecule antioxidants for hemoglobin

Cited by 19 publications

References 42 publications

Determination of the iron bioavailability, conformation, and rheology of iron‐binding proteins from Tegillarca granosa

Determination of the iron bioavailability, conformation, and rheology of iron‐binding proteins from Tegillarca granosa

Excess Ascorbate is a Chemical Stress Agent against Proteins and Cells

Study of Anticancer Drugs Interaction with Hemoglobin by Electrochemical Methods and Molecular Docking: Implications towards Anticancer Treatment

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