Yoshitake I, Kubo K
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 1991 Oct;57(2):137-45. doi: 10.1254/jjp.57.137.
The effects of KF-14363 on active oxygen production and membrane stabilization were studied. KF-14363 did not affect hypotonic hemolysis (10% and 70%) and did not inhibit lipid peroxide production induced by t-butyl hydroperoxide at concentrations of less than 100 microM. KF-14363 significantly inhibited active oxygen production in peritoneal exudate cells (PEEC) stimulated with arachidonic acid, A23187 and carbon tetrachloride (CCl4) at concentrations over 10 microM, 100 microM and 1 microM, respectively. It tended to inhibit formyl-methionyl-leucyl-phenylalanine-stimulated production of active oxygen in PEEC at concentrations over 10 microM, but there was no significant difference owing to large dispersion. Superoxide dismutase (SOD, 10(4) U/ml) significantly inhibited CCl4-stimulated production of active oxygen in PEEC. KF-14363 inhibited the radical production from CCl4 in the presence of a 9000 x g supernatant fraction of the rat liver which was administered with enzyme induction compounds (S9 mix). SOD (10(4) U/ml) was not effective in this system. In conclusion, KF-14363 inhibited active oxygen production in PEEC induced by various stimulants and also the radical formation from CCl4 in the presence of S9 mix solution.
研究了KF - 14363对活性氧生成和膜稳定性的影响。KF - 14363不影响低渗溶血(10%和70%),在浓度低于100微摩尔时不抑制叔丁基过氧化氢诱导的脂质过氧化物生成。KF - 14363在浓度分别超过10微摩尔、100微摩尔和1微摩尔时,能显著抑制花生四烯酸、A23187和四氯化碳(CCl4)刺激的腹膜渗出细胞(PEEC)中的活性氧生成。在浓度超过10微摩尔时,它倾向于抑制甲酰甲硫氨酰亮氨酰苯丙氨酸刺激的PEEC中活性氧的生成,但由于分散性大,没有显著差异。超氧化物歧化酶(SOD,10⁴单位/毫升)显著抑制CCl4刺激的PEEC中活性氧的生成。在给予酶诱导化合物(S9混合物)的大鼠肝脏9000×g上清液存在的情况下,KF - 14363抑制了CCl4产生的自由基。SOD(10⁴单位/毫升)在该系统中无效。总之,KF - 14363抑制了多种刺激物诱导的PEEC中的活性氧生成,以及在S9混合溶液存在的情况下CCl4产生的自由基形成。