Erythropoietin attenuates lipopolysaccharide-induced splenic and thymic apoptosis in rats


Koroglu T. F., Yilmaz O., Ozer E., BASKIN A. H., Gokmen N., Kumral A., ...More

PHYSIOLOGICAL RESEARCH, vol.55, no.3, pp.309-316, 2006 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 3
  • Publication Date: 2006
  • Journal Name: PHYSIOLOGICAL RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.309-316
  • Keywords: sepsis, endotoxin, lymphocyte, erythropoietin, RECOMBINANT-HUMAN-ERYTHROPOIETIN, IMPROVES SURVIVAL, CELL-DEATH, ISCHEMIA-REPERFUSION, SEPTIC SHOCK, SEPSIS, MICE, DYSFUNCTION, INJURY, OVEREXPRESSION
  • Dokuz Eylül University Affiliated: Yes

Abstract

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 143 +/- 4 (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.