Inhibition of the initial wave of NF‐κB activity in rat muscle reduces ischemia/reperfusion injury

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Abstract
Nuclear factor kappaB (NF-κB) is thought to play an important role in the expression of genes expressed in response to ischemia/reperfusion (I/R) injury. In this report, the activation of NF-κB in rat skeletal muscle during reperfusion following a 4-h ischemic period was studied. NF-κB activation displayed a biphasic pattern, showing peak activities from 30 min to 3 h postperfusion and 6 h to 16 h postperfusion, with a decline to baseline binding activity levels between 3 h and 6 h. Inhibition of NF-κB activation was investigated using proline dithiocarbamate (Pro-DTC). NF-κB binding activity during reperfusion was significantly reduced by intravenous administration of Pro-DTC. Additionally, Pro-DTC resulted in decreased muscle edema and neutrophil activity, with an increased percentage of muscle survival compared with vehicle controls. These results demonstrate that NF-κB is activated during reperfusion in a biphasic manner and that the regulation of the initial phase of NF-κB activation affords physiological protection against a severe ischemic stress. Selective inhibition of NF-κB during early reperfusion may therefore be a therapeutic intervention for I/R injury. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 534–541, 2001