Biochemical and Biophysical Research Communications
Carbamylated erythropoietin protects the kidneys from ischemia-reperfusion injury without stimulating erythropoiesis
Section snippets
Materials and methods
Experimental design. Forty-two male Sprague--Dawley rats weighing 220–280 g were purchased from Japan SLC Inc. (Shizuoka, Japan) and were maintained under standard conditions until the experiments were done. All studies were performed in accordance with the principles of the Guideline on Animal Experimentation of Osaka University. The rats were randomly allocated into three groups: (1) the saline-treatment group (control group; n = 15); (2) the EPO-treatment group (EPO group; n = 15); and (3) the
Effect on erythropoiesis and renal function
When compared to saline-treated rats, EPO-treatment (100 IU/kg × 3/wk × 2wk) significantly increased Hb concentration (saline, 13.5 ± 0.9 g/dl vs. EPO, 14.9 ± 1.0 g/dl; p < 0.01). On the other hand, CEPO-treatment neither enhanced nor reduced Hb concentration (13.1 ± 0.2 g/dl; p = 0.73), suggesting that CEPO, unlike EPO, does not stimulate erythropoiesis. Saline-treated rats demonstrated the increment of serum creatinine (1.54 ± 0.68 mg/dl) 24 h after I/R injury, and EPO-treatment showed the tendency to suppress the
Discussion
In this paper, we examined whether EPO or CEPO may have therapeutic effects on tubulointerstitial injury in a rat model of I/R injury. Untreated kidneys exhibited increased tubular apoptosis and interstitial α-SMA expression, while EPO-treatment inhibited tubular apoptosis and α-SMA expression to some extent. On the other hand, CEPO-treated kidneys showed minimal tubular apoptosis and limited α-SMA expression. In addition, CEPO administration did not increase the Hb concentration, while
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Innate and adaptive immune responses subsequent to ischemia-reperfusion injury in the kidney
2014, Progres en UrologieCitation Excerpt :A study by Imamura et al. demonstrated that EPO increased hypoxia inducible factor-1alpha (HIF-1α) expression and attenuated tubular hypoxia [83]. In an additional study, it has been shown that carbamylated EPO promoted tubular cell proliferation and decreased tubular apoptosis in a rat model of renal IRI [84]. The protective effects of heme oxygenase 1 (HO-1) in renal IRI have also been tested.
Erythropoietin regulates apoptosis, inflammation and tissue remodelling via caspase-3 and IL-1β in isolated hemoperfused kidneys
2011, European Journal of PharmacologyCitation Excerpt :EPO is safe and well tolerated for years of clinical use in patients (Maiese et al., 2005). Non-hematopoietic EPO, such as desialated EPO (asialoEPO) (Okada et al., 2007) and carbamylated EPO (CEPO) (Imamura et al., 2007), is also available and provides renoprotection in terms of inhibiting apoptosis and promoting tubular epithelial cell proliferation without erythropoiesis, although hypertension and thrombosis should not be problems for isolated kidney preservation. Our previous publication did show, after a further 3 h reperfusion, that normothermic perfusion preservation with or without EPO improved renal blood flow, serum creatinine and fractional-excretion of sodium in comparison to a continuous cold storage, but additional EPO, did not seem to add any detected functional benefits (Bagul et al., 2008a).
Erythropoietin Contrastingly Affects Bacterial Infection and Experimental Colitis by Inhibiting Nuclear Factor-κB-Inducible Immune Pathways
2011, ImmunityCitation Excerpt :In nonerythroid tissues by contrast, EPO targets a heteroreceptor complex composed of EPOR subunits assembled with beta common receptors (ßcRs), which are also utilized by other cytokine-specific and growth factor-specific receptors (Brines et al., 2004). Accordingly, EPO has been found to exert protective and antiapoptotic effects in animal models of ischemic, traumatic, and toxic tissue damage involving the nervous system, retina, myocardium, kidney, and liver (Chen et al., 2008; Digicaylioglu and Lipton, 2001; Imamura et al., 2007; Junk et al., 2002; Parsa et al., 2003; Sepodes et al., 2006). Engagement of EPOR by EPO in erythroid cells results in the induction of Janus kinase-2 (JAK2)- and signal transducer and activator of transcription-5 (STAT5)-dependent signaling cascades (Neubauer et al., 1998; Parganas et al., 1998; Zhu et al., 2008).
Carbamylated erythropoietin protects the myocardium from acute ischemia/reperfusion injury through a PI3K/Akt-dependent mechanism
2009, SurgeryCitation Excerpt :The PI3K/Akt pathway has been suggested as a downstream target of the Shh signaling pathway.21,22 Moreover, CEPO protects the kidneys from apoptosis with a concomitant up-regulation of PI3K and phosphorylation of Akt in CEPO-treated kidneys after I/R injury.6 In the present study, we showed that CEPO treatment enhanced Akt phosphorylation in the myocardium after I/R, while pretreatment with a PI3K inhibitor wortmannin abolished the CEPO-induced Akt phosphorylation.
Erythropoietin attenuates ischemia-reperfusion induced lung injury by inhibiting tumor necrosis factor-α and matrix metalloproteinase-9 expression
2009, European Journal of PharmacologyErythropoietin, Anemia and Kidney Disease
2009, Textbook of Nephro-Endocrinology