首页> 外文期刊>Experimental Biology and Medicine: Journal of the Society for Experimental Biology and Medicine >Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism
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Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism

机译:谷胱甘肽介导的机制通过2-氰基-3,12-二氧代油菜-1,9-dien-28-咪唑并保护HepG2细胞对抗丙烯醛毒性

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摘要

Acrolein is an environmental toxicant, mainly found in smoke released from incomplete combustion of organic matter. Several studies showed that exposure to acrolein can lead to liver damage. The mechanisms involved in acrolein-induced hepatocellular toxicity, however, are not completely understood. This study examined the cytotoxic mechanisms of acrolein on HepG2 cells. Acrolein at pathophysiological concentrations was shown to cause apoptotic cell death and an increase in levels of protein carbonyl and thiobarbituric acid reactive acid substances. Acrolein also rapidly depleted intracellular glutathione (GSH), GSH-linked glutathione-S-transferases, and aldose reductase, three critical cellular defenses that detoxify reactive aldehydes. Results further showed that depletion of cellular GSH by acrolein preceded the loss of cell viability. To further determine the role of cellular GSH in acrolein-mediated cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. It was observed that depletion of cellular GSH by BSO led to a marked potentiation of acrolein-mediated cytotoxicity in HepG2 cells. To further assess the contribution of these events to acrolein-induced cytotoxicity, triterpenoid compound 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) was used for induction of GSH. Induction of GSH by CDDO-Im afforded cytoprotection against acrolein toxicity in HepG2 cells. Furthermore, BSO significantly inhibited CDDO-Im-mediated induction in cellular GSH levels and also reversed cytoprotective effects of CDDO-Im in HepG2 cells. These results suggest that GSH is a predominant mechanism underlying acrolein-induced cytotoxicity as well as CDDO-Im-mediated cytoprotection. This study may provide understanding on the molecular action of acrolein which may be important to develop novel strategies for the prevention of acrolein-mediated toxicity.
机译:丙烯醛是一种环境毒物,主要存在于有机物不完全燃烧释放的烟雾中。几项研究表明,接触丙烯醛会导致肝脏损害。然而,尚未完全了解丙烯醛诱导的肝细胞毒性的机制。这项研究检查了丙烯醛对HepG2细胞的细胞毒性机制。已显示病理生理浓度的丙烯醛会导致凋亡细胞死亡,并使蛋白质羰基和硫代巴比妥酸反应性酸性物质的含量增加。丙烯醛还迅速耗尽细胞内的谷胱甘肽(GSH),GSH连锁的谷胱甘肽S-转移酶和醛糖还原酶,这是使活性醛解毒的三个关键细胞防御系统。结果进一步表明,丙烯醛对细胞内GSH的耗竭先于细胞活力的丧失。为了进一步确定细胞GSH在丙烯醛介导的细胞毒性中的作用,使用了丁硫氨酸亚砜(BSO)抑制细胞GSH的生物合成。观察到,BSO对细胞GSH的消耗导致HepG2细胞中丙烯醛介导的细胞毒性显着增强。为了进一步评估这些事件对丙烯醛诱导的细胞毒性的贡献,将三萜类化合物2-氰基-3,12-二氧代油酸-1,9-二烯基-28-咪唑啉化物(CDDO-Im)用于诱导GSH。 CDDO-Im诱导GSH提供了针对HepG2细胞中丙烯醛毒性的细胞保护作用。此外,BSO显着抑制了CDDO-Im介导的细胞GSH水平诱导,并且逆转了CDDO-Im在HepG2细胞中的细胞保护作用。这些结果表明,GSH是丙烯醛诱导的细胞毒性以及CDDO-Im介导的细胞保护作用的主要机制。这项研究可以提供对丙烯醛分子作用的理解,这对于开发预防丙烯醛介导的毒性的新策略可能很重要。

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