TY - JOUR
T1 - Significance of xanthine oxidase in the production of intracellular oxygen radicals in an in-vitro hypoxia-reoxygenation model
AU - Kakita, Tetsuya
AU - Suzuki, Masanori
AU - Takeuchi, Heigo
AU - Unno, Michiaki
AU - Matsuno, Seiki
PY - 2002
Y1 - 2002
N2 - Background/Purpose. The peroxidation of membranous phospholipids induced by ischemia reperfusion was inhibited in Cu/Zn superoxide dismutase (SOD) overexpressing mice, suggesting a detrimental role for intracellular reactive oxygen species (ROS) in reoxygenated cell injury. To ascertain the in vitro relevance of this hypothesis, the present study examined the participation of intracellular ROS in reoxygenation injury. Methods. This examination was done in two experimental models: Cu/Zn-SOD transgenic (Tg) mice that underwent hypoxia-reoxygenation in vitro and normal mice pretreated with a specific inhibitor of xanthine oxidase, BOF-4272, followed by in vitro hypoxia-reoxygenation. Results. The release of aspartate aminotransferase (AST) and the peroxidation of phospholipids were both ameliorated in hepatocytes from the Tg mice compared with findings in hepatocytes from normal mice. Similar findings were seen in the BOF-4272-pretreated cells, in which there was a decrease in AST and phospholipid peroxides. Conclusions. These results support the pivotal role of intracellular ROS generated by xanthine oxidase in reoxygenated cell injury, and suggest the viability of using an intracellular antioxidative therapy for reperfusion injury of the liver.
AB - Background/Purpose. The peroxidation of membranous phospholipids induced by ischemia reperfusion was inhibited in Cu/Zn superoxide dismutase (SOD) overexpressing mice, suggesting a detrimental role for intracellular reactive oxygen species (ROS) in reoxygenated cell injury. To ascertain the in vitro relevance of this hypothesis, the present study examined the participation of intracellular ROS in reoxygenation injury. Methods. This examination was done in two experimental models: Cu/Zn-SOD transgenic (Tg) mice that underwent hypoxia-reoxygenation in vitro and normal mice pretreated with a specific inhibitor of xanthine oxidase, BOF-4272, followed by in vitro hypoxia-reoxygenation. Results. The release of aspartate aminotransferase (AST) and the peroxidation of phospholipids were both ameliorated in hepatocytes from the Tg mice compared with findings in hepatocytes from normal mice. Similar findings were seen in the BOF-4272-pretreated cells, in which there was a decrease in AST and phospholipid peroxides. Conclusions. These results support the pivotal role of intracellular ROS generated by xanthine oxidase in reoxygenated cell injury, and suggest the viability of using an intracellular antioxidative therapy for reperfusion injury of the liver.
KW - Hepatic ischemia-reperfusion injury
KW - Lipoperoxidation
KW - Superoxide
KW - Superoxide dismutase
KW - Xanthine oxidase
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U2 - 10.1007/s005340200027
DO - 10.1007/s005340200027
M3 - Article
C2 - 12140615
AN - SCOPUS:0036078376
VL - 9
SP - 249
EP - 255
JO - Journal of Hepato-Biliary-Pancreatic Sciences
JF - Journal of Hepato-Biliary-Pancreatic Sciences
SN - 1868-6974
IS - 2
ER -