BACKGROUND: Alloantigen-independent factors contribute to long-term damage in renal transplant recipients, likely due to ischemia/reperfusion (I/R) injury at transplantation (Tx). I/R injury promotes oxidative stress and inflammation resulting in endothelial injury. METHODS: In this study we investigated the long-term efficacy (22 weeks) of short-term (10 day) endothelial protection therapy (EP) in 'optimal' donor kidneys using the male Fisher 344 rat isograft (ISO) model. ISO-EP kidneys were compared to untreated ISO (ISO-UN) kidneys. EP involved dexamethasone to donor, ex vivo treatment of the kidney with deferoxamine and tempol, and administration to the recipient of L-arginine and tempol for 10 days. Rats were sacrificed 22 weeks following Tx and compared to age-matched, normal controls. RESULTS: Both groups of ISO Tx rats developed similar renal dysfunction and structural damage and renal NADPH-oxidase-dependent O2- production was similarly elevated in ISO-UN and ISO-EP groups vs. controls. In vitro renal cortex NO synthase (NOS) activity was also similar in ISO-UN and ISO-EP rats, despite lower nNOS and eNOS protein abundance in ISO-EP. CONCLUSION: I/R injury-induced late graft dysfunction occurs even when optimal donors are used and when short-term EP treatment is given. Increased renal superoxide production is not prevented by short-term EP therapy. Copyright 2006 S. Karger AG, Basel.
BACKGROUND: Alloantigen-independent factors contribute to long-term damage in renal transplant recipients, likely due to ischemia/reperfusion (I/R) injury at transplantation (Tx). I/R injury promotes oxidative stress and inflammation resulting in endothelial injury. METHODS: In this study we investigated the long-term efficacy (22 weeks) of short-term (10 day) endothelial protection therapy (EP) in 'optimal' donor kidneys using the male Fisher 344 rat isograft (ISO) model. ISO-EP kidneys were compared to untreated ISO (ISO-UN) kidneys. EP involved dexamethasone to donor, ex vivo treatment of the kidney with deferoxamine and tempol, and administration to the recipient of L-arginine and tempol for 10 days. Rats were sacrificed 22 weeks following Tx and compared to age-matched, normal controls. RESULTS: Both groups of ISO Tx rats developed similar renal dysfunction and structural damage and renal NADPH-oxidase-dependent O2- production was similarly elevated in ISO-UN and ISO-EP groups vs. controls. In vitro renal cortex NO synthase (NOS) activity was also similar in ISO-UN and ISO-EP rats, despite lower nNOS and eNOS protein abundance in ISO-EP. CONCLUSION: I/R injury-induced late graft dysfunction occurs even when optimal donors are used and when short-term EP treatment is given. Increased renal superoxide production is not prevented by short-term EP therapy. Copyright 2006 S. Karger AG, Basel.
Authors: Lothar Schramm; Mylinh La; Ekkehart Heidbreder; Markus Hecker; Joe S Beckman; Kai Lopau; Josef Zimmermann; Johann Rendl; Christoph Reiners; Sabine Winderl; Christoph Wanner; Harald H H W Schmidt Journal: Kidney Int Date: 2002-04 Impact factor: 10.612
Authors: Ibrahim R Hanna; Lula L Hilenski; Anna Dikalova; Yoshihiro Taniyama; Sergey Dikalov; Alicia Lyle; Mark T Quinn; Bernard Lassègue; Kathy K Griendling Journal: Free Radic Biol Med Date: 2004-11-15 Impact factor: 7.376
Authors: Anja Reutzel-Selke; Thomas Zschockelt; Christian Denecke; Ulrike Bachmann; Anke Jurisch; Johann Pratschke; Georg Schmidbauer; Hans-Dieter Volk; Peter Neuhaus; Stefan G Tullius Journal: Transplantation Date: 2003-06-15 Impact factor: 4.939