Lipoic acid helps clear iron accumulation in PD model

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NHE
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Lipoic acid helps clear iron accumulation in PD model

Post by NHE » Thu Aug 27, 2020 2:38 am

Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA
Front Neurosci. 2020 Jun 25;14:612.

The disruption of neuronal iron homeostasis and oxidative stress are related to the pathogenesis of Parkinson's disease (PD). Alpha-lipoic acid (ALA) is a naturally occurring enzyme cofactor with antioxidant and iron chelator properties and has many known effects. ALA has neuroprotective effects on PD. However, its underlying mechanism remains unclear. In the present study, we established PD models induced by 6-hydroxydopamine (6-OHDA) to explore the neuroprotective ability of ALA and its underlying mechanism in vivo and in vitro. Our results showed that ALA could provide significant protection from 6-OHDA-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and iron. ALA significantly promoted the survival of the dopaminergic neuron in the 6-OHDA-induced PD rat model and remarkably ameliorated motor deficits by dramatically inhibiting the decrease in tyrosine hydroxylase expression and superoxide dismutase activity in the substantia nigra. Interestingly, ALA attenuated 6-OHDA-induced iron accumulation both in vivo and in vitro by antagonizing the 6-OHDA-induced upregulation of iron regulatory protein 2 and divalent metal transporter 1. These results indicated that the neuroprotective mechanism of ALA against neurological injury induced by 6-OHDA may be related to the regulation of iron homeostasis and reduced oxidative stress levels. Therefore, ALA may provide neuroprotective therapy for PD and other diseases related to iron metabolism disorder.

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Re: Lipoic acid helps clear iron accumulation in PD model

Post by Petr75 » Thu Aug 27, 2020 6:12 am

2020 Aug 6
Portland Health Care System, Research and Development Service, Veterans' Hospital Rd, Portland
Lipoic acid modulates inflammatory responses of monocytes and monocyte-derived macrophages from healthy and relapsing-remitting multiple sclerosis subjects
https://pubmed.ncbi.nlm.nih.gov/32762092/

Abstract

Multiple Sclerosis (MS) is a disabling neuro-inflammatory disease. Its etiology is unknown, but both oxidative stress and inflammation appear to be involved in disease pathology. Macrophages are the predominant cell type in acute inflammatory brain lesions in MS. Macrophages produce pro-inflammatory and toxic molecules that promote demyelination and are key players in phagocytosis/degradation of myelin sheathes. Lipoic acid (LA) is an inexpensive, endogenously-produced small molecule that exhibits antioxidant and anti-inflammatory effects. Treatment with LA is protective in MS and other inflammatory diseases. To examine the mechanism(s) by which LA may attenuate inflammatory lesion activity in MS, we used healthy control and MS cells to evaluate the effects of LA on levels of inflammatory cytokines, phagocytosis, and the immunomodulator cyclic AMP (cAMP) in monocytes and monocyte-derived macrophages (MDM). LA treatment resulted in a generally less inflammatory phenotype of monocytes and MDM from HC, and (to a lesser degree) MS donors. LA inhibited monocyte secretion of cytokines relevant to MS in monocytes, including TNF-α, IL-6 and IL-1β; LA effects on secretion of these cytokines in MDM was mixed with inhibition of TNF-α and IL-6, but stimulation of IL-1β, the latter perhaps due to altered macrophage polarization. LA inhibited phagocytosis in both monocytes and MDM, and increased cAMP levels in monocytes. LA may modulate inflammatory cytokine secretion and phagocytosis via a cAMP-mediated mechanism.

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Re: Lipoic acid helps clear iron accumulation in PD model

Post by NHE » Wed Dec 02, 2020 4:26 am

α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload
Int J Mol Sci. 2019 Jan 31;20(3):609.

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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Re: Lipoic acid helps clear iron accumulation in PD model

Post by NHE » Wed Dec 02, 2020 4:46 am

Role of Combined Lipoic Acid and Vitamin D3 on Astrocytes as a Way to Prevent Brain Ageing by Induced Oxidative Stress and Iron Accumulation
Oxid Med Cell Longev. 2019 Feb 28;2019:2843121.

Brain ageing is a complex multifactorial process characterized by gradual and continuous loss of neuronal functions. It is hypothesized that at the basis of brain ageing as well as age-related diseases, there is an impairment of the antioxidant defense system leading to an increase of oxidative stress. In this study, two different biological aspects involved in brain ageing and neurodegeneration have been investigated: oxidative stress and iron accumulation damage. In primary mouse astrocytes, the stimulation with 50 μM lipoic acid (LA) and 100 nM vitamin D (vitD) was first investigated in a time-course study to determine the dosages to be used in combination and then in a permeability test using an in vitro blood-brain barrier. In a second set of experiments, the role of oxidative stress was investigated pretreating astrocytes with 200 μM H2O2 for 30 min. The ability of vitD and LA alone and combined together to prevent or repair the damage caused by oxidative stress was investigated after 24 h of stimulation by the MTT test, mitochondrial membrane potential measurement, and Western blot analysis. To induce neurodegeneration, cells were pretreated with 300 μM catalytic iron for 6 days and then treated with vitD and LA alone and combined for additional 6 days to investigate the protection exerted by combination, analyzing viability, ROS production, iron concentration, and activation of intracellular pathways. In our study, the combination of LA and vitD showed beneficial effects on viability of astrocytes, since the substances are able to cross the brain barrier. In addition, combined LA and vitD attenuated the H2O2-induced apoptosis through the mitochondrial-mediated pathway. The combination was also able to counteract the adverse conditions caused by iron, preventing its accumulation. All these data support the hypothesis of the synergistic and cooperative activity exerted by LA and vitD in astrocytes indicating a possible new strategy to slow down ageing.

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