Kang M Y, Tsuchiya M, Packer L, Manabe M
Department of Anesthesiology and Resuscitology, Kochi Medical School, Nankoku, Japan.
Acta Anaesthesiol Scand. 1998 Jan;42(1):4-12. doi: 10.1111/j.1399-6576.1998.tb05073.x.
Since surgical trauma not only intensifies the oxidative stress by generating reactive oxygen species (ROS), but also weakens the biological defense system against ROS attack, the antioxidant activity of drugs used during the perioperative period, which possibly normalizes the impaired redox state in the patient, is of fundamental importance and great clinical interest.
We have applied the phycoerythrin fluorescence-based assay, in which 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-generated peroxyl radical attacks B-phycoerythrin (B-PE) to lead to a sensitive decrease in its fluorescence intensity linearly, to evaluate the antioxidant activity of major drugs in anesthetic practice.
By the protective effect on B-PE fluorescence decay, the antioxidant activities of the drugs were classified into three groups: Group I drugs, which only slowed B-PE fluorescence decay (nicardipine, verapamil, diltiazem, ephedrine, aminophylline, vecuronium, lidocaine, mepivacaine, midazolam, thiamylal, droperidol, ketamine, hydroxyzine, butorphanol, prednisolone, hydrocortisone, betamethasone, dexamethasone, methylprednisolone, and furosemide); Group II drugs, which protected B-PE oxidation completely and stopped fluorescence decay in a certain duration (dopamine, epinephrine, norepinephrine, dobutamine, isoproterenol, and buprenorphine); and Group III drugs, which had no protective effect on B-PE oxidation (nitroglycerin, prostaglandin E1, neostigmine, pancuronium, suxamethonium, atropine, bupivacaine, pentazocine, and heparin).
These results indicate that Group I and II drugs exert some antioxidant activity in vitro, as measured by their protection of fluorescence decay of B-PE. Careful consideration of these properties might, then, serve to facilitate more efficient drug application.
手术创伤不仅通过产生活性氧(ROS)加剧氧化应激,还会削弱机体针对ROS攻击的生物防御系统,因此围手术期使用的药物的抗氧化活性至关重要且具有极大的临床意义,因为这些药物可能使患者受损的氧化还原状态恢复正常。
我们应用了基于藻红蛋白荧光的检测方法,即2,2'-偶氮二(2-脒基丙烷)二盐酸盐(AAPH)产生的过氧自由基攻击β-藻红蛋白(B-PE),导致其荧光强度线性敏感下降,以此评估麻醉实践中主要药物的抗氧化活性。
通过对B-PE荧光衰减的保护作用,药物的抗氧化活性被分为三组:第一组药物,仅减缓B-PE荧光衰减(尼卡地平、维拉帕米、地尔硫䓬、麻黄碱、氨茶碱、维库溴铵、利多卡因、甲哌卡因、咪达唑仑、硫喷妥钠、氟哌利多、氯胺酮、羟嗪、布托啡诺、泼尼松龙、氢化可的松、倍他米松、地塞米松、甲泼尼龙和呋塞米);第二组药物,完全保护B-PE氧化并在一定时间内阻止荧光衰减(多巴胺、肾上腺素、去甲肾上腺素、多巴酚丁胺、异丙肾上腺素和丁丙诺啡);第三组药物,对B-PE氧化无保护作用(硝酸甘油、前列腺素E1、新斯的明、泮库溴铵、琥珀胆碱、阿托品、布比卡因、喷他佐辛和肝素)。
这些结果表明,通过对B-PE荧光衰减的保护作用来衡量,第一组和第二组药物在体外具有一定的抗氧化活性。仔细考虑这些特性可能有助于更有效地应用药物。