Protective properties of novel S-acyl-glutathione thioesters against ultraviolet-induced oxidative stress.

Abstract:

:UV-induced toxicity is characterized by marked oxidative stress, accompanied by the depletion of key cellular antioxidants, particularly glutathione (GSH). Replenishing cellular GSH may represent a means of counteracting UV-induced toxicity: however, treatment with free GSH is not therapeutically effective due to its unfavorable pharmacokinetic properties. In this study, we show that S-acyl-glutathione (acyl-SG) derivatives, which consist of an acyl chain (of variable length and saturation) linked via a thioester bond to GSH, increase intracellular levels of reduced GSH in primary skin fibroblasts, adenocarcinoma HeLa and neuroblastoma SH-SY5Y cells. Consistent with this, acyl-SG derivatives protect against UV-induced reactive oxygen species (ROS) production and UV-B/C-mediated lipid peroxidation and caspase-3 activation in the analyzed cell lines, with unsaturated thioesters displaying a significantly greater protective effect. Taken together, our findings suggest that acyl-SG thioesters may be therapeutically effective in the treatment of UV-related skin disorders and oxidative stress-mediated conditions in general.

journal_name

Photochem Photobiol

authors

Wright D,Zampagni M,Evangelisti E,Conti S,D'Adamio G,Goti A,Becatti M,Fiorillo C,Taddei N,Cecchi C,Liguri G

doi

10.1111/j.1751-1097.2012.01231.x

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

442-52

issue

2

eissn

0031-8655

issn

1751-1097

journal_volume

89

pub_type

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