Role of the vitamin E model compound Trolox in the prevention of Cr(VI)-induced cellular damage

Poljšak, Borut; Gazdag, Zoltán; Pesti, Miklós; Filipič, Metka; Fujs, Štefan; Farkas, Nelli; Plesničar, S.; Raspor, Peter

doi:10.1080/02772240500456680

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…Four reaction mechanisms have been reported to significantly contribute to the OH• scavenging capacity of Trolox in aqueous solution: hydrogen transfer (HT), radical adduct formation (RAF), single electron transfer (SET) and sequential proton loss electron transfer (SPLET) 62 . The free radical scavenging capacity of Trolox has been shown to reduce oxidative stress in aqueous systems as well as epithelial cells, hepatic injury and red blood cells in vitro and in vivo [70][71][72][73][74] . Fluorescein, organic compound used in this assay, has characteristic of high photostability, stability at physiological pH and is highly sensitive to OH• attacks.…”

Section: Discussionmentioning

confidence: 99%

PolyRad – Protection Against Free Radical Damage

Kim

Tse

Webb

et al. 2020

Sci Rep

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The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H 2 o 2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H 2 o 2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H 2 o 2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dosedependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration ~ 0.01 mg ml / (g ml 10 /). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications. As NASA prepares for exploration missions beyond low Earth orbit with no opportunities for resupply, pharmaceutical instability may present significant risk to the crew health due to the loss of efficacy over time. Astronauts suffer from sleep disruption during space flight that can affect their mental and physical health in performing routine work 1-4. Therefore, mitigation against the effects of space radiation on pharmaceutical drugs is necessary for the success of long-term space missions. NASA is primarily concerned with the he...

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Section: Discussionmentioning

confidence: 99%

PolyRad – Protection Against Free Radical Damage

Kim

Tse

Webb

et al. 2020

Sci Rep

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“…Trolox (6-hydroxy-2, 5, 7, 8-tetramethylchromane-2-carboxylic acid) is a water-soluble analogue of the free radical scavenger a-tocopherol. Trolox has advantages over a-tocopherol, which is lipid soluble because it can be incorporated in both the water and the lipid compartments of cells [17][18][19].…”

Section: Cell Treatmentmentioning

confidence: 99%

SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival

Becatti

Fiorillo

Barygina

et al. 2014

J Cellular Molecular Medi

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Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage.

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“…have claimed that the antioxidant property of Trolox surpasses that of α-tocopherol. [ 13 ] Many studies investigated the protective effect of Trolox,[ 14 – 16 ] but the mechanisms underlying these effects remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe

et al. 2010

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The ability of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), a water-soluble vitamin E analogue, to prevent oxidative damages is well characterized, but the mechanisms underlying it remain unclear. The protective effect of Trolox pre-treatment on H2O2-induced toxicity might be attributed to the decreased cellular permeability to H2O2 or in vitro scavenging activity of Trolox, induction of antioxidant enzymes or the direct scavenging activity of Trolox. The results obtained rule out the first and second possibilities and intracellular scavenging activity was found to be the mechanism whereby Trolox confers protection. This was confirmed by measuring protein oxidation (levels), and the observed decrease in proteasomal activity indicated that the decrease in protein carbonyls was due to Trolox scavenging activity rather than proteasome activation. In conclusion, the intracellular scavenging activity of Trolox is a key protective mechanism against H2O2. These findings obtained in Schizosaccharomyces pombe, a good model organism for eukaryotic cells, can be used as standard protocols for investigating the antioxidant activity of pure or complex potential antioxidants.

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Role of the vitamin E model compound Trolox in the prevention of Cr(VI)-induced cellular damage

Cited by 6 publications

References 45 publications

PolyRad – Protection Against Free Radical Damage

PolyRad – Protection Against Free Radical Damage

SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival

Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe

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