Erythropoietin Attenuates
Lipopolysaccharide-Induced Splenic and Thymic Apoptosis in Rats
T. F. KOROGLU1, O. YILMAZ2,
E. OZER3, H. BASKIN4, N. GOKMEN5,
A. KUMRAL1, M. DUMAN1, H. OZKAN1
1Department of Pediatrics, 2Animal
Research Laboratory, 3Department of Pathology, 4Department
of Microbiology, 5Department of Anesthesiology, Dokuz
Eylul University School of Medicine, Izmir, Turkey
Received April 4, 2005
Accepted July 5, 2005
On-line available August 5, 2005
Summary
Apoptosis of lymphoid tissues during sepsis is well documented
and linked to the pathobiology of organ failure and death. In
this study, we evaluated the effect of a single dose of
recombinant erythropoietin (EPO) on thymic and splenic apoptosis
in an endotoxic sepsis model. Young male Wistar rats were
divided into 3 groups and administered intraperitoneally (IP)
either normal saline; lipopolysaccharide (LPS) 10 mg/kg; or EPO
(5000 U/kg) 30 min before lipopolysaccharide. Six hours
following LPS administration animals were sacrificed. Apoptosis
was assessed by hematoxylin-eosin staining, terminal
deoxynucleotide transferase-mediated fluorescein-dUTP nick end
labeling (TUNEL), and caspase-3 immunostaining. When compared
with animals given LPS, animals pretreated with EPO displayed
reduced splenic and thymic TUNEL positivity of 44±3
(p<0.05) and 1434 (p<0.05) nuclei per high power field (hpf),
respectively. Caspase-3 positivity was also significantly
reduced in the spleen and thymus, with 31±4
(p<0.05) and 93±3 (p<0.05) positive
stained nuclei per hpf, respectively. Serum nitrite levels were
elevated in animals given lipopolysaccharide. Pretreatment with
EPO attenuated the increase in nitrite levels; however, this did
not reach statistical significance. We conclude that a single
dose of recombinant erythropoietin can reduce thymic and splenic
apoptosis associated with lipopolysaccharide administration.
Key words
Sepsis • Endotoxin • Lymphocyte • Erythropoietin
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