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

You Lin Tain, V. Müller, Attila Szabo, Anna Dikalova, Kathy Griendling, Chris Baylis

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalAmerican Journal of Nephrology
Volume26
Issue number3
DOIs
Publication statusPublished - Jul 2006

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Isografts
Reperfusion Injury
Anti-Inflammatory Agents
Antioxidants
Transplants
Kidney
United Nations
Therapeutics
Tissue Donors
Deferoxamine
Isoantigens
NADPH Oxidase
Group Psychotherapy
Nitric Oxide Synthase
Superoxides
Dexamethasone
Arginine
Oxidative Stress
Transplantation

Keywords

  • Antioxidant
  • Ischemia/reperfusion
  • Kidney transplant
  • Nitric oxide

ASJC Scopus subject areas

  • Nephrology

Cite this

Lack of long-term protective effect of antioxidant/anti-inflammatory therapy in transplant-induced ischemia/reperfusion injury. / Tain, You Lin; Müller, V.; Szabo, Attila; Dikalova, Anna; Griendling, Kathy; Baylis, Chris.

In: American Journal of Nephrology, Vol. 26, No. 3, 07.2006, p. 213-217.

Research output: Contribution to journalArticle

Tain, You Lin ; Müller, V. ; Szabo, Attila ; Dikalova, Anna ; Griendling, Kathy ; Baylis, Chris. / Lack of long-term protective effect of antioxidant/anti-inflammatory therapy in transplant-induced ischemia/reperfusion injury. In: American Journal of Nephrology. 2006 ; Vol. 26, No. 3. pp. 213-217.
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AB - 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.

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