Kourounakis A P, Rekka E A, Kourounakis P N
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece.
J Pharm Pharmacol. 1997 Sep;49(9):938-42. doi: 10.1111/j.2042-7158.1997.tb06140.x.
The effect of guaiazulene, a lipophilic azulene derivative widely found in nature, on radical-mediated processes is examined. The ability of guaizulene to inhibit rat hepatic microsomal membrane lipid peroxidation and to scavenge hydroxyl radicals, as well as to interact with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), was estimated. It was found that guaiazulene can inhibit lipid peroxidation very significantly, having an IC50 value of 9.8 microM. It can also scavenge hydroxyl radicals and interact with DPPH. The protection afforded by guaiazulene to rats with paracetamol-induced liver injury was also investigated. Paracetamol hepatotoxicity is caused by the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which causes oxidative stress and glutathione (GSH) depletion. Hepatic cytosolic protein, GSH, glutathione transferase and glutathione reductase levels are determined as indices of hepatic injury with or without the administration of guaiazulene. It was found that all parameters affected by paracetamol are restored to normal by guaiazulene treatment, while the administration of guaiazulene alone has no effect on the performed tests compared with the control values. It was concluded that the significant protection against paracetamol-induced GSH depletion and hepatic damage afforded by guaiazulene is probably connected with its antioxidant activity. A molecular mechanism of action of guaiazulene is suggested.
研究了愈创蓝油烃（一种在自然界中广泛存在的亲脂性薁衍生物）对自由基介导过程的影响。评估了愈创蓝油烃抑制大鼠肝微粒体膜脂质过氧化、清除羟自由基以及与1,1-二苯基-2-苦基肼自由基（DPPH）相互作用的能力。结果发现，愈创蓝油烃能够非常显著地抑制脂质过氧化，IC50值为9.8微摩尔。它还能清除羟自由基并与DPPH相互作用。还研究了愈创蓝油烃对扑热息痛诱导的肝损伤大鼠的保护作用。扑热息痛的肝毒性是由活性代谢产物N-乙酰对苯醌亚胺（NAPQI）引起的，它会导致氧化应激和谷胱甘肽（GSH）耗竭。测定肝胞质蛋白、GSH、谷胱甘肽转移酶和谷胱甘肽还原酶水平，作为给予或不给予愈创蓝油烃时肝损伤的指标。结果发现，愈创蓝油烃治疗可使所有受扑热息痛影响的参数恢复正常，而与对照值相比，单独给予愈创蓝油烃对所进行的测试没有影响。得出的结论是，愈创蓝油烃对扑热息痛诱导的GSH耗竭和肝损伤的显著保护作用可能与其抗氧化活性有关。提出了愈创蓝油烃的分子作用机制。
