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Effects of hydroxyethyl-starch-bound deferoxamine on ischemia/reperfusion injury in chronic nerve compression
P C Marin1, M J Im, J A Girotto
1Division of Plastic, Reconstructive and Maxillofacial Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract:
The authors have demonstrated previously that pretreatment with deferoxamine, an iron chelator and antioxidant, at the time of release in acute nerve compression, provided protection against ischemia/reperfusion (I/R) injury. In the present study, they evaluated whether therapeutic intervention with hydroxyethyl-starch-bound deferoxamine (HES-DFO) at the time of release of the chronically-compressed peripheral nerve protects the nerve from I/R injury. The sciatic nerves of 43 male Sprague-Dawley rats, weighing 325 to 350 g, were subjected to 8 weeks of compression with Silastic tubing. The treatment group received intravenous HES-DFO (70 mg/kg) at the time of decompression, while the control group received an equal volume of intravenous hetastarch vehicle at the same time schedule and route. Nerve-tissue samples from the compression site, as well as contralateral noncompressed nerves, were assayed for malondialdehyde (MDA), a marker of I/R injury. The control group exhibited MDA levels up to five times normal, and did not return to normal for 21 days. In contrast, the HES-DFO group had MDA levels that were not statistically significantly different from normal levels. The results confirm that pretreatment with HES-DFO prior to the surgical decompression of chronically-compressed nerve provides marked protection against I/R injury.