• Eduardo Cuesta, Jordi Boada, Roser Calafell, Jose C Perales, Teresa Roig, and Jordi Bermudez.
• Unitat de Biofísica, Departament de Ciències Fisiològiques II, IDIBELL, Universitat de Barcelona, Spain.
• Crit. Care Med. 2006 Mar 1; 34 (3): 807-14.

ObjectiveFructose 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.DesignProspective, controlled laboratory study.SettingAnimal resource facilities and research laboratory.SubjectsMale Sprague-Dawley rats (200-250 g body weight).InterventionsThe 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.Measurements And Main ResultsThe 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.ConclusionsThe 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.

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