Chen Ruei-Ming, Wu Gong-Jhe, Chang Hwa-Chia, Chen Jue-Tai, Chen Tzeng-Fu, Lin Yi-Ling, Chen Ta-Liang
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 111, Hsing-Lung Rd., Sec. 3, Taipei 116, Taiwan.
Ann N Y Acad Sci. 2005 May;1042:448-59. doi: 10.1196/annals.1338.038.
2,6-Diisopropylphenol is an intravenous anesthetic agent used for induction and maintenance of anesthesia. Since it is similar to alpha-tocopherol, 2,6-diisopropylphenol may have antioxidant effects. Osteoblasts play important roles in bone remodeling. In this study, we attempted to evaluate the protective effects of 2,6-diisopropylphenol on oxidative stress-induced osteoblast insults and their possible mechanisms, using neonatal rat calvarial osteoblasts as the experimental model. Clinically relevant concentrations of 2,6-diisopropylphenol (3 and 30 microM) had no effect on osteoblast viability. However, 2,6-diisopropylphenol at 300 microM time-dependently caused osteoblast death. Exposure to sodium nitroprusside (SNP), a nitric oxide donor, increased amounts of nitrite in osteoblasts. 2,6-Diisopropylphenol did not scavenge basal or SNP-releasing nitric oxide. Hydrogen peroxide (HP) enhanced levels of intracellular reactive oxygen species in osteoblasts. 2,6-Diisopropylphenol significantly reduced HP-induced oxidative stress. Exposure of osteoblasts to SNP and HP decreased cell viability time-dependently. 2,6-Diisopropylphenol protected osteoblasts from SNP- and HP-induced cell damage. Analysis by a flow cytometric method revealed that SNP and HP induced osteoblast apoptosis. 2,6-Diisopropylphenol significantly blocked SNP- and HP-induced osteoblast apoptosis. Administration of SNP and HP increased caspase-3 activities. However, 2,6-diisopropylphenol significantly decreased SNP- and HP-enhanced caspase-3 activities. This study shows that a therapeutic concentration of 2,6-diisopropylphenol can protect osteoblasts from SNP- and HP-induced cell insults, possibly via suppression of caspase-3 activities.
2,6-二异丙基苯酚是一种用于诱导和维持麻醉的静脉麻醉剂。由于它与α-生育酚相似，2,6-二异丙基苯酚可能具有抗氧化作用。成骨细胞在骨重塑中起重要作用。在本研究中，我们试图以新生大鼠颅骨成骨细胞为实验模型，评估2,6-二异丙基苯酚对氧化应激诱导的成骨细胞损伤的保护作用及其可能机制。临床相关浓度的2,6-二异丙基苯酚（3和30微摩尔）对成骨细胞活力没有影响。然而，300微摩尔的2,6-二异丙基苯酚会随时间依赖性地导致成骨细胞死亡。暴露于一氧化氮供体硝普钠（SNP）会增加成骨细胞中亚硝酸盐的含量。2,6-二异丙基苯酚不能清除基础状态或释放SNP的一氧化氮。过氧化氢（HP）会提高成骨细胞内活性氧的水平。2,6-二异丙基苯酚能显著降低HP诱导的氧化应激。将成骨细胞暴露于SNP和HP会随时间依赖性地降低细胞活力。2,6-二异丙基苯酚可保护成骨细胞免受SNP和HP诱导的细胞损伤。通过流式细胞术分析发现，SNP和HP会诱导成骨细胞凋亡。2,6-二异丙基苯酚能显著阻断SNP和HP诱导的成骨细胞凋亡。给予SNP和HP会增加caspase-3的活性。然而，2,6-二异丙基苯酚能显著降低SNP和HP增强的caspase-3活性。本研究表明，治疗浓度的2,6-二异丙基苯酚可能通过抑制caspase-3活性来保护成骨细胞免受SNP和HP诱导的细胞损伤。
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