Effect of pheniramine maleate on rat skeletal muscle ischemia-reperfusion injury

BACKGROUND: Skeletal muscle ischemia-reperfusion injury (IRI) is a common clinical problem encountered after tourniquet application or replantation. This study investigated the effect of pheniramine maleate (Ph), which is frequently used in clinical practice to reduce IRI, and compared its efficacy in IRI with N-acetylcysteine (NAC), a molecule that has been shown to be effective in IRI. METHODS: Twenty-eight male Sprague–Dawley rats were randomly divided into four groups (sham, ischemia-reperfusion [IR], IR+Ph, IR+NAC; n=7 rats per group). Ischemia was induced in the lower right extremities of rats for 3 h using a femoral artery clamp and an elastic tourniquet. Ph and NAC were administered intraperitoneally 15 min before ischemia was terminated. At 24 h after reperfusion, levels of thiobarbituric acid reactive substance (TBARS), catalase (CAT), myeloperoxidase (MPO), superoxide dismutase (SOD), polyadenosine diphosphate ribose polymerase (PARP), and neutrophil infiltration were evaluated. Inducible nitric oxide synthase (iNOS) density in muscle tissue was evaluated by immunohistochemical methods after 1 week. RESULTS: SOD, MPO, PARP, CAT, and TBARS levels in muscle tissue were significantly lower in the sham group compared with the other groups (p<0.001). All parameters except TBARS were lower in the NAC and Ph groups than in the IR group (p<0.001). Neutrophil infiltration in the muscle tissue samples from the IR group was significantly increased compared with the NAC and Ph groups (p<0.05). iNOS staining was not observed in the sham and NAC groups. CONCLUSION: Ph is effective at reducing experimental rat skeletal muscle IRI.