The effect of a nitroxide antioxidant on ischemia-reperfusion injury in the rat in vivo hind limb model

David Arieli, Guy Nahmany, Nardi Casap, Dean Ad-El, Yuval Samuni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Microsurgical procedures such as free tissue transfer or replantations of amputated digits involve an obligatory ischemic period leading to regional tissue oedema, rhabdomyolysis, systemic acidosis, hypercalcemia and multiple organ dysfunction syndrome reflecting ischemia-reperfusion (I/R) injury. Since nitroxide stable radicals act as antioxidants their potential protective effects were tested. Anaesthetized Sabra rats were subjected to regional ischemia of the hind limb for 2 h using a tourniquet. Upon reperfusion rats were injected with 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL). Systemic I/R-induced damage was assessed by sampling blood for differential count, lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels. Regional injury was evaluated by analysing excised muscle samples for oedema (tissue water content) and inflammatory infiltrate (number of cell nuclei in histomorphometric analysis). I/R-induced changes of biomarkers reflecting systemic damage peaked about 8 h following the start of reperfusion and fully disappeared as the biomarkers relaxed to their pre-ischemic values after 24 h. TPL facilitated the recovery of some of these parameters and partially affected release of cellular CPK and LDH. The parameters of I/R-induced regional tissue injury did not demonstrate any recovery and were not inhibited by TPL.

Original languageEnglish
Pages (from-to)114-123
Number of pages10
JournalFree Radical Research
Issue number2
StatePublished - Feb 2008
Externally publishedYes


  • Ischemia/reperfusion
  • Nitroxide
  • Oxidative stress
  • Rat hind limb


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