Combination Of Ischemic Post-Conditioning With A Synthetic Glycine Derivative Improves Functional Outcome After Ischemic-Reperfusion Injury In Rats

To investigate the effects of combined treatment with ischemic post-conditioning and infusion of nitroxide derivative glycine-nitronyl nitroxide conjugate (GNN) in hind limb ischemic-reperfusion animal model, male Wistar rats were randomly allocated into 5 groups: 1) sham-operated group; 2) Ischemia/reperfusion (I/R) group; 3) I/R injury + GNN alone; 4) Ischemic post-conditioning at the onset of reperfusion combined with saline; 5) Ischemic post-conditioning combined with i.v. administration of GNN (ischemic post-conditioning + GNN). At 4 h post-insult, the apoptotic cell distribution in liver, kidney and muscle tissues, the levels of malondialdehyde (MDA), myeloperoxidase (MPO) and serum tumor necrosis factor-alpha (TNF-alpha) levels, as well as the degree of muscle damage were evaluated. Compared to controls, animals treated with GNN could significantly attenuate cellular apoptosis in kidney and muscle tissues. Meanwhile, muscular inflammation, edema and damage levels were also decreased in the combined treatment group. On the other hand, the upregulation of MDA, MPO and TNF-alpha induced by ischemia were also significantly suppressed by combined treatment. These results demonstrate that combination of ischemic post-conditioning and the pharmaceutical agent (GNN) may provide an effective therapeutic strategy in acute and transient ischemic damage.