title: Fructose 1,6-bisphosphate reduced TNF-alpha-induced apoptosis in galactosamine sensitized rat hepatocytes through activation of nitric oxide and cGMP production.
abstract: Fructose 1,6-P2 (F1,6BP) protects rat liver against experimental hepatitis induced by galactosamine (GalN) by means of two parallel effects: prevention of inflammation, and reduction of hepatocyte sensitization to tumour necrosis factor-alpha (TNF-alpha). In a previous paper we reported the underlying mechanism involved in the prevention of inflammation. In the present study, we examined the intracellular mechanisms involved in the F1,6BP inhibition of the apoptosis induced by TNF-alpha in parenchyma cells of GalN-sensitized rat liver. We hypothesized that the increased nitric oxide (NO) production in livers of F1,6BP-treated rats mediates the antiapoptotic effect. This hypothesis was evaluated in cultured primary rat hepatocytes challenged by GalN plus tumour necrosis factor-alpha (GalN+TNF-alpha), to reproduce in vitro the injury associated with experimental hepatitis. Our results show a reduction in apoptosis concomitant with an increase in NO production and with a reduction in oxidative stress. In such conditions, guanylyl cyclase is activated and the increase in cGMP reduces the TNF-alpha-induced apoptosis in hepatocytes. These results provide new insights in the protective mechanism activated by F1,6BP and confirm its interest as a hepatoprotective agent.
authors.affiliation: Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Calafell
authors.forename: Jordi
authors.initials: J
authors.lastname: Boada
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Santidrian
authors.forename: Joan
authors.initials: J
authors.lastname: Gil
authors.forename: Teresa
authors.initials: T
authors.lastname: Roig
authors.forename: Jose C
authors.initials: JC
authors.lastname: Perales
authors.forename: Jordi
authors.initials: J
authors.lastname: Bermudez