Caffeic Acid Phenethyl Ester (CAPE): Scavenger of
Peroxynitrite In Vitro and In Sepsis Models
Shock, 2014 Mar 21
Excessive free radical production by immune cells has been
linked to cell death and tissue injury during sepsis. Peroxynitrite is a
short-lived oxidant and a potent inducer of cell death that has been identified
in several pathological conditions. CAPE is an active component of honeybee
products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities.
The present study examined the ability of CAPE to scavenge peroxynitrite in RAW
264.7 murine macrophages stimulated with LPS/IFN-γ, was used as an in vitro
model. Conversion of 123-dihydrorhodamine (123-DHR) to its oxidation product
123-rhodamine was used to measure peroxynitrite production. Two mouse models of
sepsis (endotoxemia and cecal ligation and puncture), were used as in vivo
models. The level of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite.
The results demonstrated that CAPE significantly improved the viability of
LPS/IFN-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide
production with effects similar to those observed with an inhibitor of
inducible nitric oxide synthase (1400W). In addition, CAPE exclusively
inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1
and directly prevented the peroxynitrite-mediated conversion of
dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In
both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as
evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of
peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to
cell damage and, potentially, cell death through suppression of the production
of cytotoxic molecules such as nitric oxide and peroxynitrite.
These
observations provide evidence of the therapeutic potential of CAPE treatment
for a wide range of inflammatory disorders.
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