Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 3, May-June, p. 321–329

Publication type: original article

Language: English

Evaluation of the Effects of a High Dose of Erythropoietin-beta on Early Endotoxemia Using a Rat Model

Ocena działania dużych dawek erytropoetyny beta na wczesną endotoksemię na modelu szczurzym

Zehra Eren1,, Jale Çoban2,, Işın D. Ekinci3,, Cigdem Kaspar4,, Gülçin Kantarcı1,

1 Department of Nephrology, Yeditepe University Hospital, İstanbul, Turkey

2 Department of Biochemistry, Yeditepe University Hospital, İstanbul, Turkey

3 Department of Pathology, Yeditepe University Hospital, İstanbul, Turkey

4 Department of Biostatistics, Yeditepe University Hospital, İstanbul, Turkey

Abstract

Background. Endotoxins can cause serious organ damage and death by triggering the secretion of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β in bacterial infections.
Objectives. The goal of this study was to evaluate the effects of a high dose (3000 U/kg) of erythropoietinbeta (EPO) on inflammatory cytokine levels, renal function and histological changes during the early period of Lipopolysaccharide (LPS)-induced endotoxemia using a rat model.
Material and Methods. Male Sprague Dawley (350–400 g) rats were randomized into 3 groups: Control group (n = 7); LPS group (received 20 mcg/kg LPS through intraperitoneal (i.p.) injection (n = 7); LPS+EPO group (received 3000 U/kg, ip 30 minutes before LPS administration (n = 7). Four hours after the administration of LPS, kidney tissue and serum samples were collected. Kidney function parameters, TNF-α, IL-6, IL-1β, C reactive protein (CRP) and complete blood counts (CBC) were measured. The severity of renal tubular injury and caspase9 immunoreactive cells was expressed as a percentage.
Results. Serum levels of urea, creatinine, TNF-α, IL-6 and IL-1β were significantly increased in the LPS group (p < 0.0001 – p = 0.04) and were lower in LPS+EPO group (p < 0.0001, p = 0.01, p = 0.02, p = 01 and p < 0.0001, respectively). Pretreatment with EPO significantly increased platelet counts (p = 0.00) and decreased white blood cell counts (p = 0.02). The renal tubular injury percentage was significantly higher in the LPS group than in the control and LPS+EPO groups (p = 0.002, p = 0.003, and p = 0.005, respectively) and caspase-9 expression was lower in the LPS+EPO and control groups than in the LPS group.
Conclusion. EPO might have renoprotective effects against the inflammatory process and cell apoptosis during endotoxemia.

Streszczenie

Wprowadzenie. Endotoksyny mogą powodować poważne uszkodzenia narządów i zgon, wywołując wydzielanie cytokin prozapalnych, takich jak TNF-a, IL-6 i IL-1b, w zakażeniach bakteryjnych.
Cel pracy. Ocena wpływu dużej dawki (3000 U/kg) erytropoetyny beta (EPO) na stężenie cytokin zapalnych, czynność nerek i zmiany histologiczne podczas wczesnej endotoksemii wywołanej przez lipopolisacharyd (LPS) na modelu szczurzym.
Materiał i metody. Szczury szczepu Sprague Dawley (350–400 g) przydzielono losowo do 3 grup: grupy kontrolnej (n = 7); grupy LPS (zwierzętom podano 20 mcg / kg LPS dootrzewnowo (ip) (n = 7)); grupę LPS + EPO (zwierzętom podano 3000 U / kg, ip 30 minut przed podaniem LPS (n = 7)). 4 godziny po podaniu LPS pobrano tkanki nerek oraz próbki surowicy. Zmierzono wskaźniki czynności nerek, TNF-alfa, IL-6, IL-1b, białko C-reaktywne (CRP) oraz morfologię krwi (CBC). Ciężkość uszkodzenia kanalików nerkowych i komórek immunoreaktywnej kaspazy-9 wyrażono w procentach.
Wyniki. Stężenie mocznika, kreatyniny, TNF-a, IL-6 i IL-1b było znacznie zwiększone w grupie LPS (p < 0,0001 – p = 0,04) i było mniejsze w grupie LPS + EPO (p < 0,0001, p = 0,01; p = 0,02; p = 01 i p < 0,0001). Wstępne podanie EPO znacznie zwiększyło liczbę płytek krwi (p = 0,00) i zmniejszyło liczbę białych krwinek (p = 0,02). Odsetek uszkodzenia kanalików nerkowych był znacznie większy w grupie LPS niż w grupie kontrolnej i grupie LPS + EPO (p = 0,002; p = 0,003 oraz p = 0,005), a ekspresja kaspazy-9 była mniejsza w grupie LPS + EPO i kontrolnej niż w grupie LPS.
Wnioski. EPO może wywierać działanie ochronne przed procesem zapalnym i apoptozą komórek podczas endotoksemii.

Key words

erythropoietin, lipopolysaccharide, endotoxemia, acute kidney injury

Słowa kluczowe

erytropoetyna, lipopolisacharyd, endotoksemia, ostra niewydolność nerek

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