Iron Poisoning
Sam Kacew in Drug Toxicity and Metabolism in Pediatrics, 1990
The serum iron level is another major determinant in the decision to institute aggressive therapy in cases of iron intoxication. The utility of serum iron determinations has been a source of controversy for many years. Critical to an understanding of the use of serum iron concentrations is an appreciation of the role of the total iron-binding capacity (TIBC). The iron-binding proteins in serum are regulated physiologically, but generally allow 200 to 300 μg/dl or iron-binding capacity. In theory, iron toxicity is more likely to occur when the serum iron concentration exceeds the ability of plasma proteins to bind it. In practice, however, the correlation between toxicity and iron-binding capacity appears to be relatively poor. The iron-binding capacity primarily measures a high-affinity binding site. Lower binding affinities may be present, as well as rapid transfer to iron-binding sites in liver and tissue that can remove free iron from the circulation. Occasionally, unusual results of TIBC may occur. Thus, the use of TIBC may occasionally be unreliable in severe iron intoxication.
Natural and physical preservative systems
R. M. Baird, S. F. Bloomfield in Microbial quality assurance in cosmetics, toiletries and non-sterile Pharmaceuticals, 2017
Iron binding proteins have been shown to inhibit the growth of certain bacteria (Schade and Caroline 1944). The three main iron binding proteins are transferrin from serum, lactoferrin from milk and ovotransferrin from avian egg white (Griffiths 1986). The depletion of iron from these environments to levels of 10−18 M is sufficient to prevent microbial survival. There are many different mechanisms, however, by which microorganisms can survive and grow in these iron-depleted environments. Some microorganisms have low iron requirements which reduces the effectiveness of the iron binding proteins (Reiter and Oram 1968). Others can attack and degrade the protein (Carlsson et al. 1984) or produce siderophores that remove iron from the protein (Perry and San Clémente 1979). This resistance has been observed in P. aeruginosa (Cox et al. 1981) which is possibly not surprising when the wide adaptability of the pseudomonads is considered.
Molecular Imaging of Reporter Genes
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Iron is an essential nutrient for the functionality and viability of cells. Due to its ability to mediate one-electron exchange reactions, iron participates in many metabolic pathways and is required for the proper function of numerous essential proteins, such as the heme-containing proteins, electron transport chain, and microsomal electron transport protein.114–116 However, the reactivity of iron may also be detrimental for living cells, as free hydroxyl radicals are generated through an iron-catalyzed Fenton reaction. Thus, maintenance of iron homeostasis is essential for the survival of animals, plants, and microorganisms.114 In the course of evolution, specialized iron-binding proteins have been evolved, allowing iron to be maintained in a thermodynamically stable form, but also kinetically available for biological processes;114 among these proteins are ferritin, transferrin, and the transferrin receptor (Figure 11.2).
SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control
Published in Journal of Dietary Supplements, 2023
Sreus A.G. Naidu, Roger A. Clemens, A. Satyanarayan Naidu
LF regulates both pro-inflammatory and anti-inflammatory responses (171); thereby could prevent viral insult-induced ‘cytokine storm’ (186). The anti-inflammatory activity of LF is associated with its ability to enter host cell nucleus and inhibit the synthesis of proinflammatory cytokine genes. Both IL-6 and IL-1β levels are elevated during inflammation due to up-regulation of cytosolic ferritin, down-regulation of FPN, membrane-bound ceruloplasmin, and TfR1 (172). This inflammatory response results in intracellular iron overload that may increase host susceptibility to infections and manifest as blood iron deficiency (i.e. anemia). Establishing the Fe-R-H by rebalancing iron levels between tissues/secretions and blood anemia could be critical during inflammation. Iron-binding proteins such as LF, TF, and ferritin play a pivotal role in human ferrokinetics (187). LF is an effective down-regulator of both IL-6 and IL-1β, as well as in preventing the activation of FPN, membrane-bound ceruloplasmin, cytosolic ferritin, and TfR1 in macrophages (52, 188). LF also activates plasminogen that regulates coagulation cascade and antithrombotic activity, a common clinical condition observed in SARS-CoV-2 infection (189,190).
Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2
Published in Expert Review of Anti-infective Therapy, 2021
Masoumeh Sadat Mousavi Maleki, Mosayeb Rostamian, Hamid Madanchi
Transferrins are iron-binding proteins with antiviral activity. The most well-known transferrin is lactoferrin (LF), which is a multifunctional 80-kDa glycoprotein and is widely available in various secretory fluids. LF, first discovered in cow’s milk, is evolutionarily highly conserved and is found in humans, mice, and pigs. Its structure consists of a polypeptide chain that has a positively charged N-terminal region. The LF chain has two circular loops connected to three spiral α-helixes, each of which has an iron-binding site. There is a strong connection between two loops when iron binds (the holo-form), which makes LF resistant to proteolysis [40]. Reports have indicated that bovine lactoferrin is a potent inhibitor of a broad number of viruses and has higher antiviral effects than human lactoferrin. Lactoferrin specifically binds to the subunit A2 of the hemagglutinin and inhibits influenza virus infection and related hemagglutination [63]. Lactoferrin has been shown to inhibit infection by binding to adenovirus III and IIIa structural polypeptides targets [64]. The inhibitory effect of LF on DENV [65], Marek’s Disease Virus (MDV) [66], and HCV [67] has been investigated. Recent studies showed that LF can interfere with some of the receptors involved in SARS-CoV-2 pathogenesis and also prevents the entering of the virus via ACE2 to host cells [68]. Therefore, LF may contribute to the prevention and treatment of COVID-19 [68].
Selected application of peptide molecules as pharmaceutical agents and in cosmeceuticals
Published in Expert Opinion on Biological Therapy, 2019
Manica Negahdaripour, Hajar Owji, Mahboobeh Eslami, Mozhdeh Zamani, Bahareh Vakili, Soudabeh Sabetian, Navid Nezafat, Younes Ghasemi
In animals, AMPs are one of the first lines of innate immune system against pathogens. It is believed that they protect tissues from airborne pathogens [85]. Defensins, as the first animal AMPs with bactericidal activity, were isolated from rabbit leukocytes. They are the most researched animal AMPs and have been categorized into α and β-defensins [86]. Human leukocytes can also produce AMPs such as α-defensins and cathelicidin LL-37 in their lysosomes [87,88]. Indolicidins and cathelicidins are antimicrobial peptides that have been isolated from neutrophils [86]. Lactoferrins, also known as lactotransferrins, are iron-binding proteins, which are found in various exocrine secretions such as milk, tears, saliva, and urine. They have shown antimicrobial activity against a wide range of pathogens [89,90]. Bombinins, the antimicrobial and hemolytic peptides from epithelia [91], and bombinin-like peptides from the skin [92] were also proposed as AMPs due to their antimicrobial activities. Furthermore, dermaseptin-1 from skin of the frog is an AMP with a potent antimicrobial activity against multiple Leishmania species [93].
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