Increased Oxidative Stress and Xanthine Oxidase Activity in Human Ruptured Cerebral Aneurysms

Abstract

Recent studies have suggested that oxidative stress may be involved in the development of arterial aneurysms. Xanthine oxidase is implicated in the generation of reactive oxygen species under pathological conditions in the cardiovascular system, and increased xanthine oxidase activity has been reported in human aortic aneurysms. We, therefore, studied the changes of xanthine oxidase activity and oxidative stress in human ruptured cerebral aneurysms. Six cerebral aneurysmal samples were obtained during surgery. Normal arteries of the similar size (one superficial temporal artery, four uterine arteries and three right gastroepiploic arteries) were used as controls. The xanthine oxidase activity was measured with a commercial assay kit, and its expression was localized by immunohistochemistry. The xanthine oxidase activity was significantly increased in aneurysms by 4.1 fold (P<0.05) compared to control arteries. This was accompanied by an elevated malondialdehyde (MDA) level (8.3±5.1 versus 2.9±0.7 nmol/g protein, mean ±SD, P<0.05), a marker of oxidative stress. Immunohistochemistry established that xanthine oxidase was mainly expressed in infiltrating inflammatory cells. Our study indicates that xanthine oxidase may have an important role in the increased oxidative stress in ruptured cerebral aneurysms. Further studies are needed to clarify the role of XO-derived reactive oxygen species in the development and rupture of cerebral aneurysms.