Lack of long-term protective effect of antioxidant/anti-inflammatory therapy in transplant-induced ischemia/reperfusion injury.
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.


CONCLUSIONS
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.
Tain
You-Lin
YL
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA. tainyl@ufl.edu
Muller
Veronika
V
Szabo
Attila
A
Dikalova
Anna
A
Griendling
Kathy
K
Baylis
Chris
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000975:Antioxidants