| Co-Investigator(Kenkyū-buntansha) |
OKA Takakazu Kyushu University, Dept.of Psychosom.Med, Assistant Professor, 大学院・医学研究院, 助手 (60291514)
SHIODA Seiji Showa University, Dept.of Anatomy, Professor, 医学部, 教授 (80102375)
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| Research Abstract |
In this project, we intended to clarify the sourcer of nitric oxides in the body during and after environmental stresses. Main results are summarized as follows.
(1) We have established the assay system for measurement of both nitric oxides and 8-hydroxy-2-deoxgunaosin (8OHdG) in in vivo and in vitro experiment.
(2) The contents of nitric oxides was as follows ; Urine : 127lmM, Plasma : 43.6, Ileum : 42.4, Liver : 28.3, Brain : 15.4.
(3) LPS ip injection induced plasma NOx increased at least two hour after injection in mice. And NOx elevation was continued until 24 hour after the injection. Both IL-1 KO mice and inhibition of HO-1 activity in BALB/c mice suppressed the LPS-induced plasma NOx increase.
(4) Brain ischemia in rat and mouse induced delayed cell death in the hypocampus in the brain. The expression of the NOx and 8OHdG were enhanced 2-4days after the ischemia stress. Since induction of NOx and 8OHdG were closely related to production of radical oxygen species (ROS), these data seems to be a good marker for apoptosis of the neural cells.
(5) Vascular damages in the human brain usually induces the attack of vasospasum several days after the primary accident, then make the general condition of the patient worth. Administration of the cyclo-oxygenase inhibitor significantly in human attenuated the hyperthermia of the brain, and suppressed the elevation of the cytokines, NOR, and 8OHdG in cerebrospinal fluid. Production of the ROS via PGE pathway in patients damaged in the brain seems to initiate the catastrophe of the host-defensive functions.
(6) NOx content ; was positively correlated to the 8OHdG contents in urine. Both NOx and 8OHdG seems to be a good marker for the oxidative stress in the body exposed to the environmental stress.
(7) The measurement system for 8OHdG/dG was very useful for evaluation of mutagenesis and biological toxicity of artificial chemical substances.
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