N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why

Aldini, Giancarlo; Altomare, Alessandra; Baron, Giovanna; Vistoli, Giulio; Borsani, Luisa; Sergio, Francesco

doi:10.1080/10715762.2018.1468564

Cited by 600 publications

(546 citation statements)

References 70 publications

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“…The behaviour of NAC in showing negligible free radical photogeneration is in agreement with previous work on wool, which showed it to confer a high level of resistance to photoyellowing when applied as a rinse treatment (with oxalic acid) to optically brightened wool [27]. NAC is a powerful antioxidant with several pharmaceutical applications, including use as an mucolytic agent and as the antidote for overdoses of the analgesic paracetamol (acetaminophen) [33].…”

Section: Epr Studiessupporting

confidence: 88%

UV damage to hair and the effect of antioxidants and metal chelators

Millington

Marsh

2020

Intern J of Cosmetic Sci

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Objective To study the effects of addition of a redox metal, copper, antioxidants and metal chelators on the formation of free radicals in natural white Caucasian hair subsequently exposed to UV light. Three different methods, electron paramagnetic resonance (EPR), a fluorescent probe for hydroxyl radical formation (terephthalate) and free radical photoyellowing, were used. These methods utilized different UV sources and reaction conditions, and so can give insights into the different mechanisms of action occurring during UV oxidation of hair. In addition, this study demonstrates how antioxidants and chelators can be screened to determine whether they can protect hair from UV damage. Results The three methods gave somewhat different results, illustrating the importance of reaction conditions and wavelength on the photochemical mechanisms, and the efficacy of additives to influence these reactions. EPR results showed that N‐acetylcysteine (NAC) pre‐treatment eliminated the intensity of the signal because of sulphur and carbon free radicals in white hair both before and after exposure to UVB radiation. Doping the hair with copper ions had no effect on the intensity of the EPR signal under dry conditions. Terephthalate fluorescent probe data showed that under wet conditions, irradiation of white hair with UVA produced significant amounts of hydroxyl radicals. Pre‐treatment of hair with NAC reduced the number of •OH radicals produced by natural white hair compared to an untreated control. In contrast to the EPR result, white hair doped with copper ions produced significantly higher levels of •OH radicals under wet conditions. It appears that the ability of copper ions to catalyse the photogeneration free radicals in hair is highly dependent on water content. Photoyellowing data showed a benefit for oxalic acid but no difference for NAC and an increase in yellowing for EDTA. Conclusion The micro‐EPR and terephthalate fluorescent probe methods are both effective techniques to study production of free radicals by hair exposed to UV light under wet and dry conditions, respectively. Both assays are simple methods for determining the effectiveness of potential protective hair treatments against UV damage, but because they assess free radical damage under dry vs wet conditions, the chemistry created on UV exposure is different. This gives insights into mechanism of action, but results may not be consistent between the two methods for actives added for reduction of UV damage. NAC pre‐treatment did reduce free radical generation in UV‐exposed hair under both wet and dry conditions. Photoyellowing data are more complicated as it is a less direct measure of UV damage and is highly dependent on irradiation source. Using UVB irradiation is experimentally convenient but may not be appropriate, because UVB wavelengths comprise only 0.3% of terrestrial sunlight. The photochemistry of hair exposed to sunlight involves concurrent photobleaching and photoyellowing processes and is far more complex. Under UVB irradiation condit...

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Section: Epr Studiessupporting

confidence: 88%

UV damage to hair and the effect of antioxidants and metal chelators

Millington

Marsh

2020

Intern J of Cosmetic Sci

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“…NAC is a versatile thiol molecule related to three main antioxidant mechanisms in the cell. It has both direct and indirect antioxidant effects over oxidative species, including the restorage of thiol groups and cysteine donor in Glutathione synthesis, regulating the redox state (Aldini et al, 2018). In agreement with the Trolox results, we observed a recovery of lipid peroxidation levels in frataxin-deficient cells, as well as an increment in the number of VDAC1-GRP75 interactions (FXN-138.2: untreated 100±26%, treated 506.95±100.46%) (Figure S2A-B).…”

Section: Trolox Recovers Mams Interactions and Ca 2+ Transfer Into MIsupporting

confidence: 87%

Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca²⁺homeostasis in FRDA

Rodríguez

Calap-Quintana

Lapeña-Luzón

et al. 2020

Preprint

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Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in gene FXN, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, an analysis of calcium management and of integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. In agreement, promoting mitochondrial calcium uptake was sufficient to restore several defects caused by frataxin deficiency in Drosophila Melanogaster. Remarkably, our findings describe for the first time frataxin as a member of the protein network of MAMs, where interacts with two of the main proteins implicated in endoplasmic reticulum-mitochondria communication. These results suggest a new role of frataxin, indicate that FRDA goes beyond mitochondrial defects and highlight MAMs as novel therapeutic candidates to improve patient´s conditions.

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“…1A-D). To determine if ROS were the active agent that blocked lysosome coalescence during apilimod-treatment for at least one of the four treatments used, we employed N-acetyl-L-cysteine (NAC) as an anti-oxidant during rotenone co-administration (Aldini et al, 2018). Indeed, cells co-exposed with apilimod, rotenone and NAC displayed larger lysosomes than cells treated with apilimod and rotenone alone (Fig.…”

Section: Stimulation Of Ros Suppresses Lysosome Enlargement During Acmentioning

confidence: 99%

Reactive oxygen species prevent lysosome coalescence during PIKfyve inhibition

Saffi

Tang

Fountain

et al. 2019

Preprint

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Acknowledgement:ARPE-1 (RPE) cells stably expressing clathrin heavy chain-eGFP were a kind gift from Dr.Costin Antonescu. We would also like to thank Mr. Janusan Baskararajah for technical assistance. AbstractLysosomes are terminal, degradative organelles of the endosomal pathway that undergo repeated fusion-fission cycles with themselves and other organelles like endosomes, phagosomes, and autophagosomes. Lysosome number, size and degradative flux depends on the equilibrium between fusion and fission rates. Thus, conditions that favour fusion over fission will reduce lysosome numbers while enlarging remaining lysosomes. Conversely, conditions that favour fission over fusion will cause lysosome fragmentation and increase their numbers. PIKfyve is a phosphoinositide kinase that generates phosphatidylinositol-3,5-bisphosphate to modulate several lysosomal functions. PIKfyve inhibition causes a dramatic increase in lysosome size and reduction in lysosome number, consistent with lysosome coalescence. This is thought to proceed through reduced lysosome reformation and/or fission after fusion with endosomes or other lysosomes. Previously, we observed that photo-damage during live-cell imaging prevented lysosome coalescence during acute PIKfyve inhibition. Thus, we postulated that lysosome fusion and/or fission dynamics are affected by reactive oxygen species (ROS). Here, we show that ROS generated by four independent mechanisms all arrested lysosome coalescence during PIKfyve inhibition and accelerated lysosome fragmentation during PIKfyve re-activation.However, depending on the ROS species and/or mode of production, lysosome dynamics were affected distinctly. H2O2 impaired lysosome motility and reduced lysosome fusion with phagosomes, suggesting that H2O2 prevents lysosome coalescence in PIKfyve-impaired cells by reducing lysosome fusogenecity. In comparison, inhibitors of oxidative phosphorylation, glutathione, and thioredoxin that produce superoxide, did not impair lysosome motility but instead promoted clearance of actin puncta on lysosomes formed during PIKfyve inhibition.Additionally, actin depolymerizing agents prevented lysosome coalescence during PIKfyve inhibition. Thus, we discovered that ROS can generally prevent lysosome coalescence during PIKfyve inhibition using distinct mechanisms.Bissig, C., Croisé, P., Heiligenstein, X., Hurbain, I., Lenk, G. M., Kaufman, E., Sannerud, R., Annaert, W., Meisler, M. H., Weisman, L. S., et al. (2019). PIKfyve complex regulates early melanosome homeostasis required for physiological amyloid formation. . Dense core lysosomes can fuse with late endosomes and are re-formed from the resultant hybrid organelles. . (2001). Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes. EMBO J. 20, 683-93.Cao, Q., Zhong, X. Z., Zou, Y., Murrell-Lagnado, R., Zhu, M. X. and Dong, X.-P. (2015). Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion.

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N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why

Cited by 600 publications

References 70 publications

UV damage to hair and the effect of antioxidants and metal chelators

UV damage to hair and the effect of antioxidants and metal chelators

Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca²⁺homeostasis in FRDA

Reactive oxygen species prevent lysosome coalescence during PIKfyve inhibition

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N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why

Cited by 600 publications

References 70 publications

UV damage to hair and the effect of antioxidants and metal chelators

UV damage to hair and the effect of antioxidants and metal chelators

Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca2+homeostasis in FRDA

Reactive oxygen species prevent lysosome coalescence during PIKfyve inhibition

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Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca²⁺homeostasis in FRDA