XDH and sickle cell disease: Although mechanisms whereby plasma XO activity is elevated in SHRs are not yet entirely clarified, it has been reported that XO is released from several organs into systemic circulation in a line of pathophysiology including hepatitis, hemorrhagic shock, sickle cell disease, and ischemia reperfusion (Yokoyama et al. 1990; Tan et al. 1998; Aslan et al. 2001).