Chikutei Ken-ichi, Oyama Tomohiro M, Ishida Shiro, Okano Yoshiro, Kobayashi Masako, Matsui Hiroko, Horimoto Kanna, Nishimura Yumiko, Ueno Shin-ya, Oyama Yasuo
Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8512, Japan.
Eur J Pharmacol. 2006 Jul 1;540(1-3):18-23. doi: 10.1016/j.ejphar.2006.04.037. Epub 2006 May 5.
Propofol (2,6-diisopropylphenol) is a general anesthetic possessing a neuroprotective action against oxidative stress produced by H2O2. H2O2 induces an exposure of phosphatidylserine on outer surface of cell membranes, resulting in change in membrane phospholipid arrangement, in rat thymocytes. Since propofol is highly lipophilic, the agent is presumed to interact with membrane lipids and hence to modify the cell vulnerability to H2O2. Therefore, to test the possibility, we have examined the effect of propofol on rat thymocytes simultaneously incubated with H2O2. Although propofol (up to 30 microM) alone did not significantly affect the cell viability, the agent at 10 microM started to increase the population of dead cells in the presence of 3 mM H2O2 and the significant increase was observed at 30 microM. Propofol at clinically relevant concentrations (10-30 microM) facilitated the process of cell death induced by H2O2 in rat thymocytes. However, propofol protected rat brain neurons against the oxidative stress induced by H2O2 under same experimental condition. Therefore, the action of propofol may be dependent on the type of cells.
丙泊酚(2,6 - 二异丙基苯酚)是一种全身麻醉剂,对过氧化氢产生的氧化应激具有神经保护作用。在大鼠胸腺细胞中,过氧化氢会诱导细胞膜外表面磷脂酰丝氨酸的暴露,导致膜磷脂排列发生变化。由于丙泊酚具有高度亲脂性,推测该药物会与膜脂质相互作用,从而改变细胞对过氧化氢的易感性。因此,为了验证这一可能性,我们研究了丙泊酚对与过氧化氢同时孵育的大鼠胸腺细胞的影响。尽管单独使用丙泊酚(高达30微摩尔)对细胞活力没有显著影响,但在3毫摩尔过氧化氢存在的情况下,10微摩尔的丙泊酚开始增加死亡细胞的比例,在30微摩尔时观察到显著增加。临床相关浓度(10 - 30微摩尔)的丙泊酚促进了过氧化氢诱导的大鼠胸腺细胞死亡过程。然而,在相同实验条件下,丙泊酚可保护大鼠脑神经元免受过氧化氢诱导的氧化应激。因此,丙泊酚的作用可能取决于细胞类型。