Fructose 1,6-bisphosphate prevented endotoxemia, macrophage activation, and liver injury induced by D-galactosamine in rats*
| Autor: | Jordi Boada, Teresa Roig, Jose C. Perales, Eduardo Cuesta, Jordi Bermúdez, Roser Calafell |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Potassium Channels
Fructose 1 6-bisphosphate Kupffer Cells medicine.medical_treatment Galactosamine Inflammation Pharmacology Critical Care and Intensive Care Medicine Histamine Release Rats Sprague-Dawley chemistry.chemical_compound Sepsis Intensive care Fructosediphosphates medicine Animals Immunologic Factors Liver injury Analysis of Variance Tumor Necrosis Factor-alpha business.industry Kupffer cell Fructose Liver Failure Acute Macrophage Activation medicine.disease Rats Disease Models Animal medicine.anatomical_structure Cytokine chemistry Immunology Hepatocytes Chemical and Drug Induced Liver Injury medicine.symptom business |
| Zdroj: | Critical Care Medicine. 34:807-814 |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/01.ccm.0000202016.60856.03 |
| Popis: | Fructose 1,6-bisphosphate (F1,6BP) protects organs against a wide range of challenges involving inflammation. We hypothesized that the primary action of F1,6BP is to prevent macrophage activation and cytokine release. Our aim was to determine the tissue and cellular targets for this bisphosphorylated sugar and to provide new insights into its mechanisms of action.Prospective, controlled laboratory study.Animal resource facilities and research laboratory.Male Sprague-Dawley rats (200-250 g body weight).The protective action of F1,6BP was analyzed in galactosamine (GalN)-induced hepatitis in rats. The in vivo effects of F1,6BP were evaluated by changes in transaminase activities, blood endotoxins, and tumor necrosis factor (TNF)-alpha production in GalN-challenged rats. The targets of F1,6BP to reduce macrophage response to lipopolysaccharide (LPS) were determined by correlation between changes in TNF-alpha production and K+ fluxes through cell membrane in primary cultures of Kupffer cells.The in vivo results indicate that F1,6BP treatment prevented GalN-induced injury in liver parenchymal cells. This protection was mainly associated with a reduction of the inflammatory response. F1,6BP prevention of GalN-induced endotoxemia correlated with preclusion of mast cell degranulation and histamine release that preceded the increased plasma endotoxins and liver production of TNF-alpha. In addition, F1,6BP treatment decreased sensitivity to LPS, which reduced the GalN-induced increase in TNF-alpha. The in vitro results show that F1,6BP inhibited Kupffer cell response and reduced TNF-alpha production by preventing LPS-induced K+ channel activation.The role of exogenous F1,6BP as a K+ channel modulator underlies its antihistaminic and anti-inflammatory action and increases its interest as a protective compound. |
| Databáze: | OpenAIRE |
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