Green T R, Bennett S R, Nelson V M
Department of Pathology, Oregon Health Sciences University, Portland 97201.
Toxicol Appl Pharmacol. 1994 Nov;129(1):163-9. doi: 10.1006/taap.1994.1240.
The active component of the anesthetic propofol (2,6-diisopropylphenol), which structurally resembles butylated hydroxy-toluene (BHT), a known free radical scavenger, was examined and compared to BHT with regard to its dose-dependent radical scavenging activity. Studies on the ameliorating effect of propofol in inhibiting radical production revealed that it preferentially scavenges organoradical species. In aqueous suspension it is more efficient than BHT as a free radical scavenger of riboflavin radicals and in blocking formation of malondialdehyde degradation products generated from lipid hydroperoxides of arachidonic acid. Neither propofol nor BHT showed any radical scavenging activities at concentration ranges less than 10 micrograms/ml. Propofol quenched radicals generated by photoillumination of riboflavin by 50% at 30 micrograms/ml. Under the same conditions BHT still showed no radical scavenging activity. At 50 micrograms/ml propofol the formation of malondialdehyde degradation products of arachidonic acid formed by illuminating arachidonic acid in test mixtures containing riboflavin was decreased by 38% compared to a decrease of only 24% with BHT substituted in place of propofol. The concentration of propofol required to ameliorate free radicals is approximately an order of magnitude higher than therapeutic doses of propofol used in anesthesia, suggesting that its scavenging activity during anesthesia is likely very limited.
麻醉剂丙泊酚(2,6 - 二异丙基苯酚)的活性成分在结构上类似于已知的自由基清除剂丁基化羟基甲苯(BHT),对其剂量依赖性自由基清除活性进行了研究,并与BHT进行了比较。关于丙泊酚在抑制自由基产生方面的改善作用的研究表明,它优先清除有机自由基物种。在水悬浮液中,作为核黄素自由基的自由基清除剂,它比BHT更有效,并且在阻断由花生四烯酸的脂质氢过氧化物产生的丙二醛降解产物的形成方面也更有效。在浓度低于10微克/毫升的范围内,丙泊酚和BHT均未显示出任何自由基清除活性。在30微克/毫升时,丙泊酚使核黄素光照射产生的自由基猝灭了50%。在相同条件下,BHT仍未显示出自由基清除活性。在50微克/毫升的丙泊酚浓度下,与用BHT替代丙泊酚时仅降低24%相比,在含有核黄素的测试混合物中照射花生四烯酸形成的花生四烯酸丙二醛降解产物的形成减少了38%。改善自由基所需的丙泊酚浓度比麻醉中使用的丙泊酚治疗剂量高约一个数量级,这表明其在麻醉期间的清除活性可能非常有限。