Reference - Detail
| RRC ID | 41332 |
|---|---|
| Author | Shiga M, Nishina K, Mikawa K, Obara H. |
| Title | The effects of lidocaine on nitric oxide production from an activated murine macrophage cell line. |
| Journal | Anesth Analg |
| Abstract |
UNLABELLED:Nitric oxide (NO), overproduced by activated macrophages, is important in the pathogenesis of various diseases, including septic shock and inflammatory tissue injury, as well as antibacterial host defense mechanisms. We examined the effects of lidocaine on NO production and the expression of inducible NO synthase (iNOS) protein and messenger RNA (mRNA) in activated macrophages. Murine macrophage-like cell line RAW 264 was stimulated for 8 h with lipopolysaccharide (10 mg/mL) and interferon-gamma (50 U/mL) in the presence of various concentrations of lidocaine (0-500 mg/mL). NO production was assessed by measuring levels of the stable metabolites, nitrite and nitrate (NOx), in the culture medium with an automatic analyzer using the Griess reaction. Expression of iNOS mRNA in harvested RAW 264 was quantified by Northern blot analysis using mouse iNOS complementary DNA probe. Expression of iNOS protein in the cells was assessed by Western blot analysis using anti-iNOS antibody. Lidocaine dose-dependently attenuated the increase in NOx levels in response to the stimulants. The drug at any concentration failed to decrease iNOS mRNA expression in RAW 264. Lidocaine at 500 mg/mL decreased iNOS protein levels. These data suggest that lidocaine reduced NO production in activated macrophages at multiple levels after transcription. The inhibitory site appeared to vary with the dose of lidocaine. IMPLICATIONS:Lidocaine dose-dependently inhibited nitric oxide production by activated macrophages, presumably at levels after transcription. The attenuating effect of lidocaine on organ injuries previously reported may be explained by the ability of the drug to suppress this inflammatory mediator. |
| Volume | 92(1) |
| Pages | 128-33 |
| Published | 2001-1-1 |
| DOI | 10.1097/00000539-200101000-00025 |
| PMID | 11133614 |
| MeSH | Anesthetics, Local / pharmacology* Animals Cell Line Dose-Response Relationship, Drug Drug Interactions Enzyme Induction / drug effects Interferon-gamma / antagonists & inhibitors Interferon-gamma / pharmacology Lidocaine / pharmacology* Lipopolysaccharides / antagonists & inhibitors Lipopolysaccharides / pharmacology Macrophage Activation / drug effects Macrophage Activation / physiology* Macrophages / drug effects* Macrophages / enzymology Macrophages / metabolism Mice Nitrates / metabolism Nitric Oxide / biosynthesis* Nitric Oxide Synthase / antagonists & inhibitors Nitric Oxide Synthase / biosynthesis* Nitric Oxide Synthase / genetics Nitric Oxide Synthase Type II Nitrites / metabolism RNA, Messenger / biosynthesis RNA, Messenger / genetics Recombinant Proteins |
| IF | 4.305 |
| Times Cited | 26 |
| WOS Category | ANESTHESIOLOGY |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |