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ironjustic
Mon, Nov-20-06, 17:16
http://ajpgi.physiology.org/cgi/content/full/274/6/G1031

<<snip>> The labile iron pool (LIP) increase is an essential
event that precedes oxidative cell damage <<snip>>

Institute of Toxicology, Swiss Federal Institute of Technology
and University of Zurich, CH-8603 Schwerzenbach, Switzerland

ABSTRACT

The labile iron pool (LIP) represents the nonferritin-bound,
redox-active iron that has been implicated in oxidative stress
and cell injury. Here we examined whether alterations in LIP
can be detected in cultured murine hepatocytes and whether
increases in LIP are related to the oxidative damage inflicted
by the redox cycling drug nitrofurantoin (NFT). Early changes
in LIP were monitored with the metal-sensitive fluorescent
probe calcein (CA), the fluorescence of which is quenched on
binding to iron. Short-term exposure (<1 h) to NFT reduced the
CA fluorescence signal by 30%, indicating that the amount of
LIP-associated iron had increased. Prolonged exposure (2 h) to
NFT caused oxidative cell injury. The addition of the
cell-permeable ferrous iron chelator 2,2'-bipyridyl not only
prevented the quenching of CA fluorescence but also partially
protected from NFT toxicity. It is concluded that reductive
stress-induced increase in LIP is an essential event that
precedes oxidative cell damage in intact hepatocytes.

cultured murine hepatocytes; nitrofurantoin; calcein;
reductive stress; iron chelators

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