title: Erythropoietin attenuates lipopolysaccharide-induced splenic and thymic apoptosis in rats.
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.
authors.affiliation: Department of Pediatrics, Dokuz Eylul University School of Medicine, 35340 Izmir, Turkey. tolga.koroglu@deu.edu.tr.
authors.forename: T F
authors.initials: TF
authors.lastname: Koroglu
authors.forename: O
authors.initials: O
authors.lastname: Yilmaz
authors.forename: E
authors.initials: E
authors.lastname: Ozer
authors.forename: H
authors.initials: H
authors.lastname: Baskin
authors.forename: N
authors.initials: N
authors.lastname: Gokmen
authors.forename: A
authors.initials: A
authors.lastname: Kumral
authors.forename: M
authors.initials: M
authors.lastname: Duman
authors.forename: H
authors.initials: H
authors.lastname: Ozkan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
chemical_list: D008070:Lipopolysaccharides; D009573:Nitrites; C482199:lipopolysaccharide, E coli O55-B5; D004921:Erythropoietin; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases