Anti-inflammatory and antioxidative effects of propofol on lipopolysaccharide-activated macrophages.

Sepsis is a serious and life-threatening syndrome that often occurs in intensive care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide (NO) can be overproduced, causing tissue and cell injury. Propofol is an intravenous agent used for sedation of ICU patients. Our previous study showed that propofol has immunosuppressive effects on macrophage functions. This study was designed to evaluate the anti-inflammatory and antioxidative effects of propofol on the biosyntheses of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, and NO in lipopolysaccharide (LPS)- activated macrophages. Exposure to a therapeutic concentration of propofol (50 microM), LPS (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF-alpha, IL-1beta, and IL-6 protein levels in a time-dependent manner, whereas propofol significantly reduced the levels of LPS-enhanced TNF-alpha, IL-1beta, and IL-6 proteins. Data from RT-PCR showed that LPS induced TNF-alpha, IL-1beta, and IL-6 mRNA, but propofol inhibited these effects. LPS also increased NO production and inducible nitric oxide synthase (iNOS) expression in macrophages. Exposure of macrophages to propofol significantly inhibited the LPS-induced NO biosynthesis. The present study shows that propofol, at a therapeutic concentration, has anti-inflammatory and antioxidative effects on the biosyntheses of TNF-alpha, IL-1beta, IL-6, and NO in LPS-activated macro-phages and that the suppressive effects are exerted at the pretranslational level.

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.