Kuo Jung-Hua Steven, Lin Yi-Lin, Tseng Jo-Wen
Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road, Sec. 1, Jen-Te, Tainan 717, Taiwan.
Colloids Surf B Biointerfaces. 2008 Jul 15;64(2):208-15. doi: 10.1016/j.colsurfb.2008.01.024. Epub 2008 Feb 7.
Tyloxapol is reported to prevent macrophages from reacting to endotoxin. However, the intracellular responses that tyloxapol induces in macrophages are still not fully explored. Hence, the objective of this study was to evaluate the intracellular events in macrophages treated with tyloxapol and assess the antioxidant properties of tyloxapol in endotoxin-activated macrophages. Using flow cytometry, we examined intracellular responses in macrophages: reactive oxygen species (ROS) content, mitochondria membrane potential, and cell cycle profiles. We also assessed the antioxidant properties of tyloxapol in endotoxin-activated macrophages. Kinetic hydrogen peroxide production tended to decline with increasing doses. Tyloxapol produced a progressive increase followed by a decline in superoxide anion production in macrophages with increasing doses. Tyloxapol also caused unstable fluctuations in mitochondrial membrane potential. Apoptosis had developed at higher doses after 4h of incubation time. After 2h of tyloxapol-pretreatment, tyloxapol acted as an antioxidant only at lower doses. Most tyloxapol-pretreated cells at lower doses fully recovered from the changes in superoxide anion and hydrogen peroxide production. Our findings contribute to a better understanding of the molecular action of tyloxapol in macrophages and how it protects macrophages against endotoxin.
据报道，聚氧乙烯蓖麻油可以阻止巨噬细胞对内毒素产生反应。然而，聚氧乙烯蓖麻油在巨噬细胞中诱导的细胞内反应仍未得到充分研究。因此，本研究的目的是评估用聚氧乙烯蓖麻油处理的巨噬细胞中的细胞内事件，并评估聚氧乙烯蓖麻油在内毒素激活的巨噬细胞中的抗氧化特性。我们使用流式细胞术检测了巨噬细胞中的细胞内反应：活性氧（ROS）含量、线粒体膜电位和细胞周期谱。我们还评估了聚氧乙烯蓖麻油在内毒素激活的巨噬细胞中的抗氧化特性。随着剂量增加，过氧化氢生成动力学呈下降趋势。随着剂量增加，聚氧乙烯蓖麻油使巨噬细胞中超氧阴离子生成先逐渐增加后下降。聚氧乙烯蓖麻油还导致线粒体膜电位出现不稳定波动。孵育4小时后，高剂量时出现凋亡。聚氧乙烯蓖麻油预处理2小时后，仅在低剂量时起抗氧化作用。大多数低剂量聚氧乙烯蓖麻油预处理的细胞中超氧阴离子和过氧化氢生成的变化完全恢复。我们的研究结果有助于更好地理解聚氧乙烯蓖麻油在巨噬细胞中的分子作用以及它如何保护巨噬细胞免受内毒素侵害。
