On Feb 7, 6:14 pm, Ken <flakey...@earthlink.net> wrote:snip <<

Ken .. what did I tell you shteaters .. ?

alt.kook.shteaters

Original Article

http://www.nature.com/jid/journal/v126/n10/full/5700373a.html

Caged-Iron Chelators a Novel Approach towards Protecting Skin Cells
against UVA-Induced Necrotic Cell Death
Journal of Investigative Dermatology (2006) 126, 2287–2295. doi:
10.1038/sj.jid.5700373; published online 18 May 2006
Anthie Yiakouvaki1,3, Jelena Savovi1,3, Abdullah Al-Qenaei1, James
Dowden2 and Charareh Pourzand1

1Department of Pharmacy and Pharmacology, University of Bath,
Claverton Down, Bath, UK
2Centre for Biomolecular Sciences, School of Chemistry, University of
Nottingham, University Park, Nottingham, UK
3These authors contributed equally to this work
Correspondence: Dr Charareh Pourzand, Department of Pharmacy and
Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
E-
mails: prs...@bath.ac.uk; James Dowden, james.dow...@nottingham.ac.uk

Received 4 January 2006; Revised 15 March 2006; Accepted 16 March
2006; Published online 18 May 2006.

Top of page
Abstract
Exposure of human skin cells to solar UVA radiation leads to an
immediate dose-dependent increase of labile iron that subsequently
promotes oxidative damage and necrotic cell death. Strong iron
chelators have been shown to suppress cell damage and necrotic cell
death by moderating the amount of labile iron pool (LIP), but chronic
use would cause severe side effects owing to systemic iron depletion.
Prodrugs that become activated in skin cells at physiologically
relevant doses of UVA, such as "caged-iron chelators", may provide
dose- and context-dependent release.
Herein, we describe prototypical iron chelator compounds derived from
salicylaldehyde isonicotinoyl hydrazone and pyridoxal isonicotinoyl
hydrazone and demonstrate that the intracellular LIP and subsequent
necrotic cell death of human skin fibroblasts is significantly
decreased upon exposure to a combination of the prototypical
compounds
and physiologically relevant UVA doses.
Iron regulatory protein bandshift and calcein fluorescence assays
reveal decreased intracellular LIP following irradiation of caged-
chelator-treated cells, but not in control samples where either UVA
light, or caged-chelator is absent.
Furthermore, flow cytometry shows that these compounds have no
significant toxicity in the skin fibroblasts.
This novel light-activated prodrug strategy may therefore be used to
protect skin cells against the deleterious effects of sunlight.

Who loves ya.
Tom

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