Evaluation of the effects of a high dose of erythropoietin-beta on early endotoxemia using a rat model.

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 caspase-9 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. Conclusions. EPO might have renoprotective effects against the inflammatory process and cell apoptosis during endotoxemia (Adv Clin Exp Med 2012, 21, 3, 321–329).