Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion.
We recently reported that excessive superoxide anion radical (O(2)(-)) was generated in the jugular vein during reperfusion in rats with forebrain ischemia/reperfusion using a novel electrochemical sensor and excessive O(2)(-) generation was associated with oxidative stress, early inflammation, and endothelial injury. However, the source of O(2)(-) was still unclear. Therefore, we used allopurinol, a potent inhibitor of xanthine oxidase (XO), to clarify the source of O(2)(-) generated in rats with forebrain ischemia/reperfusion. The increased O(2)(-) current and the quantified partial value of electricity (Q), which was calculated by the integration of the current, were significantly attenuated after reperfusion by pretreatment with allopurinol. Malondialdehyde (MDA) in the brain and plasma, high-mobility group box 1 (HMGB1) in plasma, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma were significantly attenuated in rats pretreated with allopurinol with dose-dependency in comparison to those in control rats. There were significant correlations between total Q and MDA, HMGB, or ICAM-1 in the brain and plasma. Allopurinol pretreatment suppressed O(2)(-) generation in the brain-perfused blood in the jugular vein, and oxidative stress, early inflammation, and endothelial injury in the acute phase of forebrain ischemia/reperfusion. Thus, XO is one of the major sources of O(2)(-)- in blood after reperfusion in rats with forebrain ischemia/reperfusion.
Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, 1-1-1, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Takeru
T
Ono
Ryosuke
R
Tsuruta
Motoki
M
Fujita
Hiromi Shinagawa
HS
Aki
Satoshi
S
Kutsuna
Yoshikatsu
Y
Kawamura
Jun
J
Wakatsuki
Tetsuya
T
Aoki
Chihiro
C
Kobayashi
Shunji
S
Kasaoka
Ikuro
I
Maruyama
Makoto
M
Yuasa
Tsuyoshi
T
Maekawa
D000493:Allopurinol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D024243:HMGB1 Protein / Q000097:blood; D007118:Immunoassay; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D024243:HMGB1 Protein; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase