BACKGROUND: Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells and is known to be up-regulated during states of hypoxia. Here we investigate the effects of renal ischemia/reperfusion (I/R) on the degree of renal dysfunction and injury with recombinant human EPO in mice when given as either a 3-day pretreatment, or upon reperfusion of the kidney. METHODS: Mice were treated with EPO (1000 IU/kg/day subcutaneously) for 3 days, or treated with EPO (1000 IU/kg subcutaneously) upon reperfusion, and subsequently subjected to bilateral renal artery occlusion (30 minutes) and reperfusion (24 hours). At the end of experiments, the following indicators and markers of renal injury and dysfunction were measured: plasma urea, creatinine, and aspartate aminotransferase (AST), tissue myeloperoxidase (MPO) activity [for polymorphonuclear leukocyte (PMN) infiltration], and tissue malonaldehyde (MDA) levels (for tissue lipid peroxidation). Kidneys were used for histologic evaluation of renal injury. RESULTS: EPO was able to significantly attenuate the renal dysfunction and injury associated with I/R, as well as the tissue injury. The increase in renal MPO activity and, hence, the degree of PMN infiltration were also significantly reduced in EPO-treated mice. In addition, lipid peroxidation as a result of renal I/R injury was also attenuated in EPO-treated mice. CONCLUSION: The protection afforded by the pretreatment regime of EPO was greater than that of administering EPO as a single bolus upon reperfusion. We propose that different mechanisms underlie the protective effects seen with EPO when given as either a daily pretreatment or as a single bolus, which need to be further investigated.
BACKGROUND:Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells and is known to be up-regulated during states of hypoxia. Here we investigate the effects of renal ischemia/reperfusion (I/R) on the degree of renal dysfunction and injury with recombinant humanEPO in mice when given as either a 3-day pretreatment, or upon reperfusion of the kidney. METHODS:Mice were treated with EPO (1000 IU/kg/day subcutaneously) for 3 days, or treated with EPO (1000 IU/kg subcutaneously) upon reperfusion, and subsequently subjected to bilateral renal artery occlusion (30 minutes) and reperfusion (24 hours). At the end of experiments, the following indicators and markers of renal injury and dysfunction were measured: plasma urea, creatinine, and aspartate aminotransferase (AST), tissue myeloperoxidase (MPO) activity [for polymorphonuclear leukocyte (PMN) infiltration], and tissue malonaldehyde (MDA) levels (for tissue lipid peroxidation). Kidneys were used for histologic evaluation of renal injury. RESULTS:EPO was able to significantly attenuate the renal dysfunction and injury associated with I/R, as well as the tissue injury. The increase in renal MPO activity and, hence, the degree of PMN infiltration were also significantly reduced in EPO-treated mice. In addition, lipid peroxidation as a result of renal I/R injury was also attenuated in EPO-treated mice. CONCLUSION: The protection afforded by the pretreatment regime of EPO was greater than that of administering EPO as a single bolus upon reperfusion. We propose that different mechanisms underlie the protective effects seen with EPO when given as either a daily pretreatment or as a single bolus, which need to be further investigated.
Authors: Kalathil K Sureshkumar; Sabiha M Hussain; Tina Y Ko; Ngoc L Thai; Richard J Marcus Journal: Clin J Am Soc Nephrol Date: 2012-06-28 Impact factor: 8.237
Authors: Andrei Todica; Mathias J Zacherl; Hao Wang; Guido Böning; Nathalie L Jansen; Carmen Wängler; Peter Bartenstein; Michael C Kreissl; Marcus Hacker; Stefan Brunner; Sebastian Lehner Journal: J Nucl Cardiol Date: 2014-09-05 Impact factor: 5.952
Authors: Michael Brines; Nimesh S A Patel; Pia Villa; Courtenay Brines; Tiziana Mennini; Massimiliano De Paola; Zubeyde Erbayraktar; Serhat Erbayraktar; Bruno Sepodes; Christoph Thiemermann; Pietro Ghezzi; Michael Yamin; Carla C Hand; Qiao-wen Xie; Thomas Coleman; Anthony Cerami Journal: Proc Natl Acad Sci U S A Date: 2008-08-01 Impact factor: 11.205
Authors: W M Bernhardt; U Gottmann; F Doyon; B Buchholz; V Campean; J Schödel; A Reisenbuechler; S Klaus; M Arend; L Flippin; C Willam; M S Wiesener; B Yard; C Warnecke; K-U Eckardt Journal: Proc Natl Acad Sci U S A Date: 2009-11-23 Impact factor: 11.205