Dexmedetomidine protects against ischemia-reperfusion injury in rat skeletal muscle

Background: Dexmedetomidine (DEX) has been shown to decrease ischemia reperfusion (I/R) injury in kidney and brain tissues. In this study, the effects of DEX were evaluated in skeletal muscle during I/R injury. Materials and methods: Animals were divided into four groups: sham-operated (sham group), saline + I/R, DEX + I/R, and alpha-tocopherol + I/R groups. Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h of ischemia, the clamp was removed and the animals underwent 2 h of reperfusion. Animals in the drug treatment group received DEX or alpha-tocopherol by intraperitoneal injection 1 h before reperfusion. We measured plasma concentrations of interleukin 1 beta and tumor necrosis factor alpha levels using an enzyme-linked immunosorbent assay. The right gastrocnemius muscle was harvested and immediately stored at -80 degrees C for the assessment of superoxide dismutase (SOD) and catalase (CAT) activities as well as glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. DEX (25 mu g/kg) and normal saline (10 mL/kg) were administered by intraperitoneal injection 1 h before reperfusion. Results: Plasma tumor necrosis factor alpha or interleukin 1 beta levels increased significantly in the I/R group (P < 0.01 compared with sham group) and decreased significantly in the DEX group (P < 0.01 compared with I/R group). Muscle tissues of the I/R group had significantly decreased SOD, GSH, and CAT activities and increased levels of MDA and PO content compared with the sham group. The activity of antioxidant enzymes in the DEX + I/R group was greatly elevated compared with that in the I/R group (SOD, 1.068 +/- 0.120 versus 0.576 +/- 0.072 U/mg protein; GSH, 2.436 +/- 0.144 versus 1.128 +/- 0.132 mu mol/g; and CAT, 69.240 +/- 6.456 versus 31.884 +/- 6.312 U/mg protein; P < 0.01), whereas the levels of MDA and PO content were clearly reduced (23.268 +/- 3.708 versus 53.604 +/- 5.972 nmol/g protein and 1.908 +/- 0.192 versus 5.208 +/- 0.612 nmol/mg protein, respectively; P < 0.01). Moreover, DEX exhibited more potent antioxidant activity than vitamin E in the skeletal muscle I/R. Conclusions: We found that DEX exhibits protective effects against skeletal muscle I/R injury. These results underscore the necessity of human studies with DEX to determine if it is beneficial for preventing skeletal muscle I/R injury. (C) 2014 Elsevier Inc. All rights reserved.