Anti-inflammatory effect of remifentanil in lipopolysaccharide-stimulated amniotic epithelial cells.

BACKGROUND: Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). METHODS: WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B (NF-κB) and p38 and the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, cyclooxygenase (COX)2, and prostaglandin E (PGE)2 were quantified using western blotting and RT-PCR, respectively. RESULTS: Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of NF-κB, and expression of COX2 and PGE2 in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of IL-1ß and TNF-α expression was also observed with RT-PCR. CONCLUSION: Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.

Remifentanil reduced the effects of hydrogen peroxide-induced oxidative stress in human keratinocytes via autophagy.

PURPOSE: Excess reactive oxygen species are detrimental to wound repair. Remifentanil decreases reactive oxygen species generation and inflammatory response; however, its effects on oxidative cell injury are not completely understood. Therefore, we investigated the effects of remifentanil on human keratinocytes under hydrogen peroxide-induced oxidative stress and the correlation of these effects with autophagy. MATERIALS AND METHODS: Human keratinocytes (HaCaT cell line) were randomly assigned to four groups: control, hydrogen peroxide, remifentanil pretreatment + hydrogen peroxide, and 3-methyladenine + remifentanil pretreatment + hydrogen peroxide. The MTT assay was performed to analyze cell viability. Apoptotic cell death was measured by Hoechst staining. A scratch assay was used to measure cell migration. The role of autophagy was ascertained by autophagosome staining and western blot analysis of autophagy-related proteins. RESULTS: Compared with the control group, the hydrogen peroxide group showed decreased cell viability, which was improved by remifentanil pretreatment. Hydrogen peroxide-induced apoptotic cell death and delayed cell migration were also improved by remifentanil pretreatment. Western blot analysis showed that the expression of autophagy-related proteins significantly increased in the remifentanil pretreatment + hydrogen peroxide group compared with that in the hydrogen peroxide group. CONCLUSIONS: This study demonstrated that remifentanil pretreatment ameliorates hydrogen peroxide-induced oxidative injury in human keratinocytes. In addition, our results show that the antioxidative effect of remifentanil against hydrogen peroxide-induced oxidative injury was mediated by autophagy.