Oxidative stress, the alteration of mitochondrial function, and changes in the neurovascular unit (NVU) could play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Our aim was to analyze the plasma redox system and nitric oxide (NO) in 25 ALS new-diagnosed patients and five healthy controls and the effects of plasma on the peroxidation/mitochondrial function in human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. In plasma, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and nitric oxide (NO) were analyzed by using specific assays. In HUVEC/astrocytes, the effects of plasma on the release of mitochondrial reactive oxygen species (mitoROS) and NO, viability, and mitochondrial membrane potential were investigated. In the plasma of ALS patients, an increase in TBARS and a reduction in GSH and NO were found. In HUVEC/astrocytes treated with a plasma of ALS patients, mitoROS increased, whereas cell viability and mitochondrial membrane potential decreased. Our results show that oxidative stress and NVU play a central role in ALS and suggest that unknown plasma factors could be involved in the disease pathogenesis. Quantifiable changes in ALS plasma related to redox state alterations can possibly be used for early diagnosis.
Hepatitis C virus (HCV) patients are at increased risk of cardiovascular disease (CVD). In this study, we aimed to evaluate the role of extracellular vesicles (EVs) as pathogenic factors for the onset of HCV-related endothelial dysfunction. Sixty-five patients with various stages of HCV-related chronic liver disease were enrolled in this case series. Plasma EVs were characterized and used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, and reactive oxygen species (ROS) release. The results showed that EVs from HCV patients were mainly of endothelial and lymphocyte origin. Moreover, EVs were able to reduce cell viability and mitochondrial membrane potential of HUVEC, while increasing ROS release. Those harmful effects were reduced by the pretreatment of HUVEC with the NLR family pyrin domain containing 3 (NLRP3)/AMP-activated protein kinase and protein kinase B blockers. In conclusion, in HCV patients, we could highlight a circulating pattern of EVs capable of inducing damage to the endothelium. These data represent a novel possible pathogenic mechanism underlying the reported increase of CVD occurrence in HCV infection and could be of clinical relevance also in relation to the widespread use of antiviral drugs.
Although recent data highlight the greater protective effects exerted by Membrane Blue Dual (MBD), a precise analysis of the mechanisms of action is missing. We examined the effects of MBD with/without polyethylene glycol (PEG) on both human retinal pigment epithelial cells (ARPE-19) and retinal ganglion cells-like (RGC-5) cultured in the presence/absence of ultraviolet B (UVB) treatment on mitochondria function, oxidants, and apoptosis. In ARPE-19/RGC-5 cells either treated or not with UVB, the effects of MBD with/without PEG were evaluated by specific assays for viability, mitochondrial membrane potential and mitochondrial reactive oxygen species (mitoROS) release. Annexin V was used to detect apoptosis, whereas trypan blue and the scratch assay were used for proliferation/migration. In both physiologic conditions and in the presence of UVB, MBD with/without PEG increased cell viability, mitochondrial membrane potential, proliferation and migration in both ARPE-19 and RGC-5 cells. In general, the effects of MBD with PEG were greater than those caused by MBD without PEG. Our results suggest that, in particular, MBD with PEG is a safe and effective dye for vitreoretinal surgery through the modulation of mitochondrial function.
Background: The management of neurodegenerative diseases can be frustrating for clinicians, given the limited progress of conventional medicine in this context. Aim: For this reason, a more comprehensive, integrative approach is urgently needed. Among various emerging focuses for intervention, the modulation of central nervous system energetics, oxidative stress, and inflammation is becoming more and more promising. Method: In particular, electrons leakage involved in the mitochondrial energetics can generate reactive oxygen-free radical-related mitochondrial dysfunction that would contribute to the etiopathology of many disorders, such as Alzheimer's and other dementias, Parkinson's disease, multiple sclerosis, stroke, and amyotrophic lateral sclerosis (ALS). Results: In this context, using agents, like acetyl L-carnitine (ALCAR), provides mitochondrial support, reduces oxidative stress, and improves synaptic transmission. Conclusion: This narrative review aims to update the existing literature on ALCAR molecular profile, tolerability, and translational clinical potential use in neurodegeneration, focusing on ALS.
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