Suppression of oxidative stress after transient focal ischemia in interleukin-1 knock out mice.
Interleukin-1 (IL-1) contributes to ischemic neurodegeneration. However, the mechanisms regulating action of IL-1 are still poorly understood. In order to clarify this central issue, mice that were gene deficient both IL-1alpha and beta (IL-1 KO) and wild-type mice were subjected to 1 hour transient middle cerebral artery occlusion (tMCAO). The concentration of 8-hydroxy deoxyguanosine (8OHdG) which is considered to be a reliable oxidative DNA damage by superoxide anion, in brain and of total nitric oxide (NO) in plasma were determined by use of HPLC. Twenty-four hours after tMCAO, the ratio of 8OHdG to dG in the ipsilateral hemisphere of wild-type mice were 2.24 x 10(-3) and 4.41 x 10(-3) in the neocortex and striatum, respectively. The concentration of 8OHdG in the ipsilateral hemisphere of the wild-type mice was higher than that of the IL-1 KO mice. The concentration of total NO in the plasma of IL-1 KO mice was also lower than that of the wild-type 24 hours after tMCAO. These results strongly suggest that IL-1 is participated in generating reactive oxygen spices and it aggravates and induces the ischemic neuronal cell death.(183 words).
Ohtaki
H
H
Department of Anatomy, Showa University School of Medicine, Tokyo, Japan. taki@med.showa-u.ac.jp
Takaki
A
A
Yin
L
L
Dohi
K
K
Nakamachi
T
T
Matsunaga
M
M
Horai
R
R
Asano
M
M
Iwakura
Y
Y
Shioda
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000401:mortality; D007375:Interleukin-1 / Q000172:deficiency*; D002546:Ischemic Attack, Transient / Q000097:blood / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress
D007375:Interleukin-1; D009566:Nitrates; D009573:Nitrites; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine