Lee Chung Soo, Kim Yun Jeong, Han Eun Sook
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
Life Sci. 2007 Apr 17;80(19):1759-67. doi: 10.1016/j.lfs.2007.02.003. Epub 2007 Feb 11.
The present study was designed to assess the preventive effect of licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid against mitochondrial damage and cell death in lung epithelial cells exposed to 3-morpholinosydnonime, a donor of nitric oxide and superoxide. Treatment of lung epithelial cells with 3-morpholinosydnonime resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. Treatment of glycyrrhizin and 18beta-glycyrrhetinic acid attenuated the 3-morpholinosydnonime-induced mitochondrial damage, formation of reactive oxygen species and GSH depletion and revealed a maximal inhibitory effect at 10 and 1 muM, respectively; beyond these concentrations the inhibitory effect declined. Melatonin, carboxy-PTIO, rutin and uric acid reduced the 3-morpholinosydnonime-induced cell death. The results show that glycyrrhizin and 18beta-glycyrrhetinic acid seem to prevent the toxic effect of 3-morpholinosydnonime against lung epithelial cells by suppressing the mitochondrial permeability transition that leads to the release of cytochrome c and activation of caspase-3. The preventive effect may be ascribed to the inhibitory action on the formation of reactive oxygen species and depletion of GSH. The findings suggest that licorice compounds seem to prevent the nitrogen species-mediated lung cell damage.
本研究旨在评估甘草化合物甘草酸和18β-甘草次酸对暴露于3-吗啉代非那明（一种一氧化氮和超氧化物供体）的肺上皮细胞线粒体损伤和细胞死亡的预防作用。用3-吗啉代非那明处理肺上皮细胞导致核损伤、线粒体跨膜电位降低、细胞色素c的胞质积累、半胱天冬酶-3激活、活性氧形成增加和谷胱甘肽耗竭。甘草酸和18β-甘草次酸处理减弱了3-吗啉代非那明诱导的线粒体损伤、活性氧形成和谷胱甘肽耗竭，分别在10 μM和1 μM时显示出最大抑制作用；超过这些浓度，抑制作用下降。褪黑素、羧基-PTIO、芦丁和尿酸减少了3-吗啉代非那明诱导的细胞死亡。结果表明，甘草酸和18β-甘草次酸似乎通过抑制导致细胞色素c释放和半胱天冬酶-3激活的线粒体通透性转变来预防3-吗啉代非那明对肺上皮细胞的毒性作用。预防作用可能归因于对活性氧形成和谷胱甘肽耗竭的抑制作用。这些发现表明，甘草化合物似乎可以预防氮物种介导的肺细胞损伤。
