Therapeutic potential of iron chelators in diseases associated with iron mismanagement

Weinberg, Eugene D.

doi:10.1211/jpp.58.5.0001

Cited by 28 publications

(16 citation statements)

References 106 publications

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“…It is well known that ELF-MF exposure affects oxidative processes in living cells [Zmyslony et al, 2004], and chelatable free iron, participating in the metabolism of reactive oxygen species, represents a potential liability to synaptosomes. During the past half century, many diseases have been associated with iron mismanagement and various pathologies have been successfully treated with iron chelators [Weinberg, 2006]. In our experimental conditions, ELF-MF exposure did not increase the release of free iron by synaptosomes, indicating the absence of induction of reactive oxygen species during and after exposure. ]…”

Section: Discussionmentioning

confidence: 59%

Synaptosome behaviour is unaffected by weak pulsed electromagnetic fields

Aldinucci

Carretta

Maiorca

et al. 2007

Bioelectromagnetics

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The present study examined the effect on rat cortical synaptosomes of a 2 h exposure to 50-Hz electromagnetic fields (EMFs) with a peak magnetic field of 2 mT. We measured modifications of synaptosomal mitochondrial respiration rate, ATP production, membrane potential, intrasynaptosomal Ca(2+) concentration and free iron release. The O(2) consumption remained unvaried in exposed synaptosomes at about 2 nM O(2)/min/mg proteins; ATP production was also unchanged. The intrasynaptosomal Ca(2+) concentration decreased slowly and there was a slight, but non-significant, depolarisation of the synaptosomal membrane. Finally, the free iron release by synaptosomal suspensions, a useful predictor of neuro-developmental outcome, remained unchanged after EMF exposure. On the whole, our results indicate that the physiological behaviour of cortical synaptosomes is not affected by weak pulsed EMFs.

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Section: Discussionmentioning

confidence: 59%

Synaptosome behaviour is unaffected by weak pulsed electromagnetic fields

Aldinucci

Carretta

Maiorca

et al. 2007

Bioelectromagnetics

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“…While both compounds have been described previously as single treatments (19)(20)(21)(22) and in combination (18), the present study is the first to incorporate Def and GaPP in a clinically relevant hydrogel, thereby potentially serving as a novel antimicrobial strategy in the context of topical biofilm-related infections. The surgical hydrogel was used as a carrier to deliver Def and GaPP to biofilms, thereby complementing the gel's wound-healing properties with antimicrobial activity for topical treatment.…”

Section: Discussionmentioning

confidence: 98%

A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity

Richter

Thomas

Claeys

et al. 2017

Antimicrob Agents Chemother

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Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While oral drug delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection site while reducing systemic side effects. This study determined the antibiofilm activity of a surgical wound gel loaded with the iron chelator deferiprone (Def) and the heme analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. Activity against MDR Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of CFU and correlative light/electron microscopy. While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gels (log 10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity against P. aeruginosa biofilms (log 10 reduction of 1.3 for GaPP and 3.3 for DefGaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds. Def-GaPP delivered in a surgical wound gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound-healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for clinical utilization as a therapy for topical biofilm-related infections.KEYWORDS antimicrobial combinations, biofilms, drug delivery, iron metabolism M edical treatments for chronic infectious diseases are typically based on oral delivery of high-dose, long-term antibiotic therapies. Despite the risk for emerging antimicrobial resistance and the potential of side effects (e.g., gastrointestinal disorders, neutropenia, nephrotoxicity), there is a lack of suitable alternatives. Depending on the disease nature and localization, topical treatments can deliver high dosages of antimicrobials directly to an infection site while reducing unwanted systemic effects. Higher drug dosages are particularly needed to combat microbial biofilms (1). The ability of bacteria to form biofilms and establish resistance to antibiotics is a major biomedical threat, adding billions of dollars to health care costs worldwide (1-3). Biofilms are responsible for 80% of microbial infections in humans and are a common cause of chronic infections, including chronic wound and chronic sinus infections (4, 5), with increasing tolerance and subtle resistance mechanisms to antibiotic therapies (6-8).

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“…In the human body, transferrin acts as an iron-transporting protein and is found predominantly in the blood, whereas lactoferrin is localized in exocrine secretes (e.g. saliva, tears, milk, bronchial mucus) and in the secondary granules of neutrophils (Weinberg 2003(Weinberg , 2006. Its role in man is only partially known.…”

Section: Introductionmentioning

confidence: 99%

The effects of lactoferrin in a rat model of catecholamine cardiotoxicity

et al. 2008

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Lactoferrin is recently under intense investigation because of its proposed several pharmacologically positive effects. Based on its iron-binding properties and its physiological presence in the human body, it may have a significant impact on pathological conditions associated with iron-catalysed reactive oxygen species (ROS). Its effect on a catecholamine model of myocardial injury, which shares several pathophysiological features with acute myocardial infarction (AMI) in humans, was examined. Male Wistar rats were randomly divided into four groups according to the received medication: control (saline), isoprenaline (ISO, 100 mg kg(-1) s.c.), bovine lactoferrin (La, 50 mg kg(-1) i.v.) or a combination of La + ISO in the above-mentioned doses. After 24 h, haemodynamic functional parameters were measured, a sample of blood was withdrawn and the heart was removed for analysis of various parameters. Lactoferrin premedication reduced some impairment caused by ISO (e.g. a stroke volume decrease, an increase in peripheral resistance and calcium overload). These positive effects were likely to have been mediated by the positive inotropic effect of lactoferrin and by inhibition of ROS formation due to chelation of free iron. The failure of lactoferrin to provide higher protection seems to be associated with the complexity of catecholamine cardiotoxicity and with its hydrophilic character.

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Therapeutic potential of iron chelators in diseases associated with iron mismanagement

Cited by 28 publications

References 106 publications

Synaptosome behaviour is unaffected by weak pulsed electromagnetic fields

Synaptosome behaviour is unaffected by weak pulsed electromagnetic fields

A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity

The effects of lactoferrin in a rat model of catecholamine cardiotoxicity

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