To investigate effects of hepatotropic growth factors on radical production in rat hepatocytes during sepsis.Rat hepatocytes, isolated by collagenase perfusion, were incubated with a lipopolysaccharide (LPS)-containing cytokine mixture of interleukin-1?, tumor necrosis factor-? and interferon-? to simulate sepsis and either co-incubated or pre-incubated with hepatotropic growth factors, e.g. hepatocyte growth factor, epidermal growth factor and/or transforming growth factor-?. Cells were analyzed for glutathione levels. Culture supernatants were assayed for production of reactive oxygen intermediates (ROIs) as well as NO(2) (-), NO(3) (-) and S-nitrosothiols. To determine cellular damage, release of aspartate aminotransferase (AST) into the culture medium was analyzed. Activation of nuclear factor (NF)-?B was measured by electrophoretic mobility shift assay.Rat hepatocytes treated with the LPS-containing cytokine mixture showed a significant increase in ROI and nitrogen oxide intermediate formation. AST leakage was not significantly increased in cells treated with the LPS-containing cytokine mixture, independent of growth-factor co-stimulation. However, pretreatment with growth factors significantly reduced AST leakage and ROI formation while increasing cellular glutathione. Application of growth factors did not result in increased NF-?B activation. Pretreatment with growth factors further increased formation of NO(2) (-), NO(3) (-) and S-nitrosothiols in hepatocytes stimulated with LPS-containing cytokine mixture. Thus, we propose that, together with an increase in glutathione increased NO(2) (-), NO(3) (-) formation might shift their metabolism towards non-toxic products.Our data suggest that hepatotropic growth factors positively influence sepsis-induced hepatocellular injury by reducing cytotoxic ROI formation via induction of the cellular protective antioxidative systems.     «

To investigate effects of hepatotropic growth factors on radical production in rat hepatocytes during sepsis.Rat hepatocytes, isolated by collagenase perfusion, were incubated with a lipopolysaccharide (LPS)-containing cytokine mixture of interleukin-1?, tumor necrosis factor-? and interferon-? to simulate sepsis and either co-incubated or pre-incubated with hepatotropic growth factors, e.g. hepatocyte growth factor, epidermal growth factor and/or transforming growth factor-?. Cells were analyze...     »