Radical scavenging activity of bisbenzylisoquinoline alkaloids and traditional prophylactics against chemotherapy-induced oral mucositis
Radical scavenging activity of bisbenzylisoquinoline alkaloids and traditional prophylactics against chemotherapy-induced oral mucositis
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DOI：
10.1111/j.1365-2710.2008.00993.x
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发表时间：
2009-04-01
影响因子：
2
通讯作者：
Makino, K.
中科院分区：
文献类型：
--
作者：
Kaji, H.;Inukai, Y.;Makino, K.
背景和目的：口腔粘膜炎是癌症患者全身化疗和放疗的主要严重毒副作用。各种自由基清除剂已被证明可以预防化疗引起的皮肤坏死。本研究的目的是确定双苄基异喹啉生物碱化合物 (BIQAC) 和一系列化学物质（包括别嘌呤醇）的抗氧化活性，临床上用于治疗化疗引起的粘膜炎。方法：测试别嘌呤醇、褪黑激素、甲磺酸卡莫司他、甲磺酸加贝酯、对苯二酚和 BIQAC 对四种不同自由基种类的自由基清除活性：使用标准方法测定1,1-二苯基-2-三硝基苯肼基(DPPH)自由基和2,2'-连氮基-双(3-乙基苯并噻唑啉-6-磺酸)阳离子自由基(ABTS(中心点+))，使用电子自旋共振测定超氧阴离子自由基(O-2(-))和羟基自由基(OH中心点)。结果：别嘌呤醇仅对O-2(-)具有自由基清除活性。褪黑素对ABTS(中心点+)有较强的自由基清除活性，对DPPH自由基和OH中心点活性较弱。甲磺酸卡莫司他对 OH 中心点具有弱的自由基清除活性。甲磺酸加贝酯对这些自由基没有自由基清除活性。对苯二酚对DPPH自由基和ABTS(中心点+)具有较强的自由基清除活性，对O-2(-)和OH中心点具有中等活性。 BIQAC对DPPH自由基具有中等的自由基清除活性，对ABTS(中心点+)和O-2(-)自由基具有较强的自由基清除活性，对OH中心点的自由基清除活性较弱。结论：BIQAC具有最广谱的自由基清除活性，提示其可能对化疗引起的粘膜炎有效。这些发现还表明，这种针对四种自由基的自由基清除活性筛选方法可能有助于筛选新的天然和合成化学品的自由基清除活性。
Background and objective: Oral mucositis is a major severe toxic side-effect of systemic chemotherapy and irradiation in patients with cancer. Various free radical scavengers have been shown to prevent chemotherapy-induced skin necrosis. The objective of this study was to determine the antioxidant activity of a bisbenzylisoquinoline alkaloidal compound (BIQAC) and a series of chemicals, including allopurinol, used clinically for the treatment of chemotherapy-induced mucositis.Methods: Allopurinol, melatonin, camostat mesilate, gabexate mesilate, hydroquinone and BIQAC were tested for their radical scavenging activities on four different radical species: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) cation radical (ABTS(center dot+)) using standard methods, and superoxide anion radical (O-2(-)) and hydroxyl radical (OH center dot) using electron spin resonance.Results: Allopurinol had radical scavenging activity against O-2(-) only. Melatonin had strong radical scavenging activity against ABTS(center dot+), and weak activity against DPPH radical and OH center dot. Camostat mesilate had weak radical scavenging activity against OH center dot. Gabexate mesilate had no radical scavenging activity against any of these radicals. Hydroquinone had strong radical scavenging activity against DPPH radical and ABTS(center dot+), and moderate activity against both O-2(-) and OH center dot. BIQAC had moderate radical scavenging activity against DPPH radical, strong radical scavenging activity against ABTS(center dot+) and O-2(-), and weak activity against OH center dot.Conclusion: The BIQAC had the most braod-spectrum radical scavenging activity, suggesting that it may be effective against chemotherapy-induced mucositis. These findings also suggest that this radical-scavenging activity screening method, against four kinds of radicals, may be useful for the screening of radical scavenging activity of new natural and synthetic chemicals.