2,6-Diisopropylphenol protects osteoblasts from oxidative stress-induced apoptosis through suppression of caspase-3 activation.
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.
Chen
Ruei-Ming
RM
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 111, Hsing-Lung Rd., Sec. 3, Taipei 116, Taiwan. rmchen@tmu.edu.tw
Wu
Gong-Jhe
GJ
Chang
Hwa-Chia
HC
Chen
Jue-Tai
JT
Chen
Tzeng-Fu
TF
Lin
Yi-Ling
YL
Chen
Ta-Liang
TL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D018384:Oxidative Stress; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D009573:Nitrites; D017382:Reactive Oxygen Species; D009599:Nitroprusside; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D015742:Propofol