Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload

Ali, Yasser; Desouky, Omar S.; Selim, Nabila S.; Ereiba, Khairy. M.

doi:10.1016/j.jrras.2014.10.009

Cited by 20 publications

(12 citation statements)

References 54 publications

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“…Interestingly, ALA is able to act inside the lysosomes, the conjugated action of cysteine and acid pH favors the rapid reduction of ALA in DHLA, possibly with the help of the lysosomal constituent, such as the lysosomal thiol reductase. Through its two vicinal thiolic groups, DHLA forms a Table 2:4 complex with Fe III (Fe 2 [DHLA] 4 ), and a less stable one with Fe II [27,28,29,30,31,32,33]. Several groups have reported that lysosomal degradation of ferritin is crucial for the utilization of ferritin iron stores in a number of different settings and plays a central role in iron extraction from ferritin.…”

Section: Discussionmentioning

confidence: 99%

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α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload

Camiolo

Tibullo

Giallongo

et al. 2019

IJMS

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Iron toxicity is associated with organ injury and has been reported in various clinical conditions, such as hemochromatosis, thalassemia major, and myelodysplastic syndromes. Therefore, iron chelation therapy represents a pivotal therapy for these patients during their lifetime. The aim of the present study was to assess the iron chelating properties of α-lipoic acid (ALA) and how such an effect impacts on iron overload mediated toxicity. Human mesenchymal stem cells (HS-5) and animals (zebrafish, n = 10 for each group) were treated for 24 h with ferric ammonium citrate (FAC, 120 µg/mL) in the presence or absence of ALA (20 µg/mL). Oxidative stress was evaluated by reduced glutathione content, reactive oxygen species formation, mitochondrial dysfunction, and gene expression of heme oxygenase-1b and mitochondrial superoxide dismutase; organ injury, iron accumulation, and autophagy were measured by microscopical, cytofluorimetric analyses, and inductively coupled plasma‒optical mission Spectrometer (ICP-OES). Our results showed that FAC results in a significant increase of tissue iron accumulation, oxidative stress, and autophagy and such detrimental effects were reversed by ALA treatment. In conclusion, ALA possesses excellent iron chelating properties that may be exploited in a clinical setting for organ preservation, as well as exhibiting a good safety profile and low cost for the national health system.

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Section: Discussionmentioning

confidence: 99%

“…Briefly, 20 µg/mL solution of acridine orange in appropriate buffer were added to100 µL of cell suspension and incubated at room temperature for 20 min. Finally, the appropriate isotopic control was also included and labeled cells were acquired using a Beckman Coulter FC-500 flow cytometer [33,34].…”

Section: Methodsmentioning

confidence: 99%

α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload

Camiolo

Tibullo

Giallongo

et al. 2019

IJMS

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“…Mean plasma half-life of α-lipoic acid is approximately 30 min following both intravenous (iv) or oral administration [ 261 ]. Ali et al (2015) reported that administration of α-lipoic acid leads to a decrease in the level of lipid peroxidation in plasma, liver, and brain [ 262 ]. This property may be attributed to its bioavailability, which it employs in counteracting oxidative species directly.…”

Section: Counteractive Antioxidant Defencementioning

confidence: 99%

Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants

Jan

Azam

Siddiqui

et al. 2015

IJMS

940

404

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Heavy metals, which have widespread environmental distribution and originate from natural and anthropogenic sources, are common environmental pollutants. In recent decades, their contamination has increased dramatically because of continuous discharge in sewage and untreated industrial effluents. Because they are non-degradable, they persist in the environment; accordingly, they have received a great deal of attention owing to their potential health and environmental risks. Although the toxic effects of metals depend on the forms and routes of exposure, interruptions of intracellular homeostasis include damage to lipids, proteins, enzymes and DNA via the production of free radicals. Following exposure to heavy metals, their metabolism and subsequent excretion from the body depends on the presence of antioxidants (glutathione, α-tocopherol, ascorbate, etc.) associated with the quenching of free radicals by suspending the activity of enzymes (catalase, peroxidase, and superoxide dismutase). Therefore, this review was written to provide a deep understanding of the mechanisms involved in eliciting their toxicity in order to highlight the necessity for development of strategies to decrease exposure to these metals, as well as to identify substances that contribute significantly to overcome their hazardous effects within the body of living organisms.

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“…79 It is involved in the reduction of Fe 3+ to Fe 2+ and may help prevent iron overload associated toxicity. 80 Treatment with lipoic acid decreased brain atrophy as measured by the percent change in brain volume in SPMS patients. 39 However, all other CNS imaging associated and clinical measures failed to show significant benefits, but may stem from lack of power due to the small sample size.…”

Section: Moving Forwardmentioning

confidence: 99%

Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS

et al. 2018

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Clinically effective immunomodulatory therapies have been developed for relapsing-remitting multiple sclerosis (RRMS), but they have generally not translated to a corresponding slowing of disability accumulation in progressive forms of multiple sclerosis (MS). Since disability is multifaceted, progressive patients are heterogeneous, and the drivers of disease progression are still unclear, it has been difficult to identify the most informative outcome measures for progressive trials. Historically, secondary outcome measures have focused on inflammatory measures, which contributed to the recent identification of immunomodulatory therapies benefiting younger patients with more inflammatory progressive MS. Meanwhile, agents capable of treating late-stage disease have remained elusive. Consequently, measures of neurodegeneration are becoming common. Here, we review completed clinical trials testing immunomodulatory therapies in primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis (SPMS) and discuss the features contributing to trial design variability in relation to trial outcomes, and how efforts toward better patient stratification and inclusion of reliable progression markers could improve outcomes.

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Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload

Cited by 20 publications

References 54 publications

α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload

α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload

Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants

Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS

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