Marianne Landmann1, Giridhar Kanuri1, Astrid Spruss2, Carolin Stahl2, Ina Bergheim3. 1. SD Model Systems of Molecular Nutrition, Friedrich-Schiller University, Jena, Germany. 2. Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany. 3. SD Model Systems of Molecular Nutrition, Friedrich-Schiller University, Jena, Germany. Electronic address: Ina.bergheim@uni-jena.de.
Abstract
OBJECTIVE: Acute and chronic consumption of alcohol can alter intestinal barrier function thereby increasing portal endotoxin levels subsequently leading to an activation of toll-like receptor (TLR) 4-dependent signaling cascades, elevated levels of reactive oxygen species and induction of tumor necrosis factor α in the liver. Recent studies suggest that chicoric acid found in Echinacea pupurea, chicory, and other plants, may possess antioxidant and anti-inflammatory effects. The aim of the present study was to determine if chicoric acid can reduce acute alcohol-induced liver damage. METHODS: Female mice were given chicoric acid orally (4 mg/kg body weight) for 4 d before acute ethanol administration (6 g/kg body weight). Furthermore, the effect of chicoric acid on the lipopolysaccharide (LPS)-dependent activation in an in vitro model of Kupffer cells (RAW264.7 macrophages) was assessed. RESULTS: Acute alcohol ingestion caused a significant increase in hepatic triacylglycerols accumulation, which was associated with increased protein levels of the inducible nitric oxide synthase (iNOS), 4-hydroxynonenal protein adducts, and active plasminogen activator inhibitor 1 protein in the liver. Pretreatment of animals with chicoric acid significantly attenuated these effects of alcohol on the liver. In LPS-treated RAW264.7 macrophages, pretreatment with chicoric acid significantly suppressed LPS-induced mRNA expression of iNOS and tumor necrosis factor α. CONCLUSION: These data suggest that chicoric acid may reduce acute alcohol-induced steatosis in mice through interfering with the induction of iNOS and iNOS-dependent signaling cascades in the liver.
OBJECTIVE: Acute and chronic consumption of alcohol can alter intestinal barrier function thereby increasing portal endotoxin levels subsequently leading to an activation of toll-like receptor (TLR) 4-dependent signaling cascades, elevated levels of reactive oxygen species and induction of tumor necrosis factor α in the liver. Recent studies suggest that chicoric acid found in Echinacea pupurea, chicory, and other plants, may possess antioxidant and anti-inflammatory effects. The aim of the present study was to determine if chicoric acid can reduce acute alcohol-induced liver damage. METHODS: Female mice were given chicoric acid orally (4 mg/kg body weight) for 4 d before acute ethanol administration (6 g/kg body weight). Furthermore, the effect of chicoric acid on the lipopolysaccharide (LPS)-dependent activation in an in vitro model of Kupffer cells (RAW264.7 macrophages) was assessed. RESULTS: Acute alcohol ingestion caused a significant increase in hepatic triacylglycerols accumulation, which was associated with increased protein levels of the inducible nitric oxide synthase (iNOS), 4-hydroxynonenal protein adducts, and active plasminogen activator inhibitor 1 protein in the liver. Pretreatment of animals with chicoric acid significantly attenuated these effects of alcohol on the liver. In LPS-treated RAW264.7 macrophages, pretreatment with chicoric acid significantly suppressed LPS-induced mRNA expression of iNOS and tumor necrosis factor α. CONCLUSION: These data suggest that chicoric acid may reduce acute alcohol-induced steatosis in mice through interfering with the induction of iNOS and iNOS-dependent signaling cascades in the liver.