Autor(es):
Costa, Pedro 
; Cunha, Lídia ; Bravo, Joana ; Alves, Cecília J. ; Summavielle, Teresa ; Metello, Luís F.
Data: 2010
Identificador Persistente: http://hdl.handle.net/10400.22/2363
Origem: Repositório Científico do Instituto Politécnico do Porto
Descrição
Introduction:
In
the XXI Century
’s
Society
the scientific investigation process has
been growing
steadily
, and the field of the pharmaceutical research is one of the most
enthusiastic
and relevant
. Here, it is very important to correlate
observed functional
alterations with possibly
modified
drug
bio
distribution
patterns
.
Cancer, inflammation and inf
ection are processes that induce many molecular
intermediates like cytokines, chemokines and other chemical complexes that can alter
the pharmacokinetics of many drugs. One cause of such changes is thought to be the
modulator action of these complexes in t
he P
-
Glyco
p
rotein
activity, because they can
act like inducers/inhibitors of MDR
-
1 expression.
This protein results from the
expression of MDR
-
1 gene, and acts as
an
ATP
energy
-
dependent efflux pump,
with
their substrates including
many drugs
,
like antiretrovirals, anticancers, anti
-
infectives,
immunosuppressants, steroids or opioids
.
Objectives:
Because of the lack of methods to provide helpful information in the
investigation of
in vivo
molecular changes in Pgp activity during infection/infl
ammation
processes, and its value in the explanation of the altered drug pharmacokinetic, this
paper
want to evaluate the potential utility of
99m
Tc
-
Sestamibi scintigraphy during this
kind of health sciences investigation.
Although the a
im
is
indeed
to
create
a technique to
the
in vivo
study of Pgp activity, this preliminary Project only reaches the
in vitro
study
phase, assumed
as the first step in a
n
evaluation period
for
a
new tool development.
Materials and Methods:
For that
reason
, we are performing
in vitro
studies of influx
and efflux of
99m
Tc
-
Sestamibi
(
that is a substrate
of Pgp)
in hepatocytes cell line
(HepG2). We are interested in clarify the cellular behavior of
this radiopharmaceutical
in Lipopolysaccharide(LPS)
stimulated
cells (
well known
in vitro
model of
inflammation) to possibly approve this methodology. To validate the results,
the
Pgp
expression will be
finally
evaluated
using
Western Blot
technique. Results:
Up to
this moment
, we
still
don’t have
the
final results, but we
have already
enough data to let us
believe that LPS stimulation induce a downregulation of MDR
-
1,
and consequently Pgp, which
could
conduce to a prolonged retention of
99m
Tc
-
Sestamibi in the
inflamed
cells
.
Conclusions:
If
and when
this methodology
demonstrate the promising results we
expect, one will be able to
con
clude that Nuclear Medicine is
an important tool to help
evidence based research
also on this specific field
.
