Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion in rabbit hind limbs

Background Glycyrrhizin, an agent that can bind to selectins and inhibit their ability to bind neutrophils, was found to be effective in preventing tissue edema caused by ischemia-reperfusion in a rabbit model. Methods Complete ischemia was produced by applying a tight Esmarch tourniquet to the hind limbs of 24 Japanese white rabbits. Immediately before and 1 h after release of the tourniquet, 12 animals were given glycyrrhizin intravenously; 12 controls received saline. Results The mean relative increase in the circumference of the shins before and after ischemia-reperfusion with or without glycyrrhizin treatment was 4.6% ± 2.4% and 9.6% ± 4.2%, respectively, indicating that tissue edema caused by the ischemia-reperfusion was significantly attenuated by glycyrrhizin. Histological studies of cross sections of the anterior tibial muscle 24 h after reperfusion showed a significant reduction in the incidence of necrotic muscle fibers in the glycyrrhizin-treated animals compared with the controls that did not receive glycyrrhizin. The mRNA levels of P- and E-selectin 24 h after reperfusion were significantly higher in the ischemic anterior tibial muscle than in the nonischemic normal muscle. After 24 h of reperfusion, the mean activity of myeloperoxidase, a neutrophil-specific enzyme, in the anterior tibial muscles of the group given glycyrrhizin (0.0022 ± 0.0013 absorbance units) was lower than that of the untreated group (0.027 ± 0.026 absorbance units). Conclusions These data suggest that glycyrrhizin treatment is effective in suppressing the acute inflammatory reaction or edema following ischemia-reperfusion and might be potentially useful in clinical practice for preventing ischemia-reperfusion injuries to the extremities.