PUVA‐Induced Cell Mortality in NCTC 2544 Keratinocytes: Is It Related to the Microenvironmental Properties of the Excited States of Psoralens?

Sousa, Cristina; Melo, Teresa Sá e; Mazière, Jean‐Claude; Santús, René

doi:10.1111/j.1751-1097.1998.tb09094.x

Cited by 11 publications

(6 citation statements)

References 27 publications

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“…The Efficacy of the Deactivation of the T 1 State by Oxygen. For several years the role of reactive oxygen species such as superoxide radicals and singlet oxygen have been discussed frequently when using 8-MOP for PUVA therapy. − …”

Section: Resultsmentioning

confidence: 99%

“…For several years the role of reactive oxygen species such as superoxide radicals and singlet oxygen have been discussed frequently when using 8-MOP for PUVA therapy. [6][7][8][9][10][11][12] To assess the role of singlet oxygen in photosensitized reactions the efficacy of singlet oxygen generation by the dye used must be determined. 27 In the first step, the efficacy P T of the T 1 state deactivation by oxygen was determined by applying eqs 5 and 9 to the measured relaxation rate constants.…”

Section: The Efficacy Of the Deactivation Of The T 1 State By Oxygenmentioning

confidence: 99%

“…In addition to the interaction with DNA, photoactivated 8-MOP generates singlet oxygen leading to photosensitizing effects of furocoumarins. , It has been shown in vivo that more than 80% of the bound 8-MOP is localized in proteins and lipids of cells immediately after irradiation with UVA . The ability of 8-MOP to form singlet oxygen is considered to be responsible for a number of side effects in PUVA therapy, such as mutagenicity, , cell membrane-damaging reactions and, therefore, oedema or erythema, , and finally inactivation of encymes or of ribosomes .…”

Section: Introductionmentioning

confidence: 99%

“…6,8 It has been shown in vivo that more than 80% of the bound 8-MOP is localized in proteins and lipids of cells immediately after irradiation with UVA. 9 The ability of 8-MOP to form singlet oxygen is considered to be responsible for a number of side effects in PUVA therapy, such as mutagenicity, 5,10 cell membrane-damaging reactions and, therefore, oedema or erythema, 7,11 and finally inactivation of encymes or of ribosomes. 12 Although the role of singlet oxygen was discussed frequently when using 8-MOP for PUVA therapy, there are hardly any detailed investigations on its generation mainly due to a low quantum yield of 2% or less.…”

Section: Introductionmentioning

confidence: 99%

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Singlet Oxygen Generation by 8-Methoxypsoralen in Deuterium Oxide: Relaxation Rate Constants and Dependence of the Generation Efficacy on the Oxygen Partial Pressure

et al. 2002

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The photoactivation of 8-methoxypsoralen (8-MOP) by ultraviolet light is widely used for the treatment of several skin diseases. The major mechanism is the intercalation of 8-MOP into nuclear DNA in the dark and subsequently the formation of monoadducts and potential cross links under UVA irradiation. In addition, the irradiation of 8-MOP leads to the generation of singlet oxygen by means of photodynamic action which has been shown to induce a critical oxidative damage of the DNA in vitro. To assess the role of singlet oxygen generated by photoactivated 8-MOP, its relaxation in solutions of deuterium oxide was studied in detail. Relaxation rates and rate constants of the involved 8-MOP triplet T 1 state and oxygen 1 ∆ g state were determined by analyzing the rise and decay rates of the luminescence of singlet oxygen at 1.27 µm. The efficacy of singlet oxygen generation is described by the singlet oxygen quantum yield Φ ∆ , which depends on the efficacy of 8-MOP T 1 state deactivation by oxygen, P T ([O 2 ]). P T ([O 2 ]) has been determined for different oxygen concentrations and decreased from 2% under aerated conditions (e.g., in vitro conditions, 130 Torr) to 0.5% for the in ViVo situation inside the skin (∼20 Torr). The efficacy of singlet oxygen generation and maybe therefore the role of singlet oxygen in the oxidative damage depends critically on the respective oxygen partial pressure. This must be considered when transferring results and conclusions from experiments in vitro or in solution to the situation in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: The Efficacy Of the Deactivation Of The T 1 State By Oxygenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Singlet Oxygen Generation by 8-Methoxypsoralen in Deuterium Oxide: Relaxation Rate Constants and Dependence of the Generation Efficacy on the Oxygen Partial Pressure

et al. 2002

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“…These photo-adducts are considered to be less toxic for keratinocytes, thus exhibiting a miniscule phototoxic reactions in the skin [34]. In other words, photoradiation accompanied by isomerization of double bonds in fatty acid molecules, photo-oxidation of phospholipids and psoralen and splitting of fatty acid adducts, all together helps in maintaining the cellular homeostasis in the stratum corneum and deeper layers of dermis [4].…”

Section: Skin Photosensitization and Histopathologymentioning

confidence: 99%

Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment

Garg

Beg

et al. 2015

Journal of Drug Targeting

100

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The present investigation aimed for the development and characterization of ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery and effective treatment against vitiligo. The ethosomes were prepared by central composite design (CCD) and characterized for various quality attributes like vesicle shape, size, zeta potential, lamellarity, drug entrapment and drug leaching. The optimized ethosomes were subsequently incorporated int Carbopol® 934 gel and characterized for drug content, rheological behavior, texture profile, in vitro release, ex vivo skin permeation and retention, skin photosensitization and histopathological examination. Ethosomes were found to be spherical and multilamellar in structures having nanometric size range with narrow size distribution, and high encapsulation efficiency. Ethosomal formulations showed significant skin permeation and accumulation in the epidermal and dermal layers. The fluorescence microscopy study using 123 Rhodamine exhibited enhanced permeation of the drug-loaded ethosomes in the deeper layers of skin. Also, the developed formulation showed insignificant phototoxicity and erythema vis-à-vis the conventional cream. The results were cross-validated using histopathological examination of skin segments. In a nutshell, the ethosomes-based hydrogel formulation was found to be a promising drug delivery system demonstrating enhanced percutaneous penetration of methoxsalen with reduced phototoxicity and erythema, thus leading to improved patient compliance for the treatment against vitiligo.

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The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

Lakatos

Hegedűs

Ayestarán

et al. 2016

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5J/cm(2)) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ-34+UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and -8. In conclusion, PJ-34 is a photosensitizer and PJ-34+UVA causes DNA damage and caspase-mediated cell death independently of PARP-1 inhibition.

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PUVA‐Induced Cell Mortality in NCTC 2544 Keratinocytes: Is It Related to the Microenvironmental Properties of the Excited States of Psoralens?

Cited by 11 publications

References 27 publications

Singlet Oxygen Generation by 8-Methoxypsoralen in Deuterium Oxide: Relaxation Rate Constants and Dependence of the Generation Efficacy on the Oxygen Partial Pressure

Singlet Oxygen Generation by 8-Methoxypsoralen in Deuterium Oxide: Relaxation Rate Constants and Dependence of the Generation Efficacy on the Oxygen Partial Pressure

Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

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