Free Radical Research, Vol. 35, pp. 907 916
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© 2001 OPA (Overseas Publishers Association) N.V.
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Changes in the Ascorbic Acid Levels of Peritoneal
Lymphocytes and Macrophages of Mice with Endotoxin-
induced Oxidative Stress
VICTOR M. VICTOR, NOELIA GUAYERBAS, MARTA PUERTO and MONICA DE LA FUENTE*
Department of Animal Physiology, Faculty of Biology, Complutense University, Av. Complutenses/n, E-28040Madrid, Spain
Accepted by Professor A. Azzi
(Received 1 March 2001; In revised form 30 March 2001)
Ascorbic acid (AA) is an important cytoplasmic
antioxidant that mice synthesize in the liver, the
intracellular levels of which decrease in an oxidative
stress situation such as endotoxic shock. The present
work deals with the changes in AA levels, that
modulate the immune ffmction, in the two main
immune cells, namely macrophages and lymphocytes,
from female BALB/c mice suffering endotoxic shock
caused by intraperitoneal injection of Escherichia coli
lipopolysaccharide (LPS) (100mg/kg). The intake by
cells of this antioxidant present in vitro at different
concentrations was also studied. The animals show
an oxidative stress, standardized in previous studies,
that causes mortality at 30 h after LPS injection. The
cells were obtained from the peritoneum at 2, 4, 12
and 24h after LPS or PBS (control) injections and
were incubated without or with AA at 0.01, 0.1 and
I mM for 10, 30, 60, 120 or 180 min. The hepatic AA
levels were also studied at 0, 2, 4, 12 and 24h after
LPS injection. The peritoneal cells obtained from
animals injected with LPS showed increased AA
levels in relation to the control cells at all times after
LPS injection, with maximal effect at 12h. The AA
levels decreased after this time, in agreement with
changes in the AA hepatic levels. The increase was
due to the AA of lymphocytes since macrophages
showed a decrease in AA at different times after LPS
injection. Both cells showed an increase in the
intracellular levels of AA when this antioxidant was
added in vitro. This takes place mainly at 30-60min
of incubation in cells from controls and at 10 min in
cells from treated mice 12-24h after LPS injection.
The incorporation decreased at these times of
endotoxic shock, a few hours before death. In all
cases AA levels were higher in lymphocytes than in
macrophages, and l mM was the most effective
concentration. These results suggest that the immtme
cells need appropriate levels of antioxidants, such as
AA, under oxidative stress conditions, and that while
lymphocytes take and accumulate AA, macrophages
use it.
Keywords: Ascorbic acid; Macrophages; Lymphocytes;
Oxidative stress
*Corresponding author. Tel.: +34-91-394-4989. Fax: +34-91-394-4935. E-mail: mondelaf@bio.sim.ucm.es
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