Green tea suppresses lipopolysaccharide-induced liver injury in D-galactosamine-sensitized rats

Abstract

We conducted a series of in vivo experiments to clarify the hepatoprotective activity of green tea against lipopolysaccharide (LPS) + D-galactosamine (GaIN)-induced liver injury and to elucidate the mechanism by which green tea exerts its effect in 7-wk-old male Wistar rats. Liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities. Green tea extract significantly suppressed LPS + GaIN-induced liver injury when added to the diet (30 or 35 g/kg) and fed to rats for 14 d or when force-fed alone (0.4-1.2 g/kg body) 1.5 h before the injection of drugs. Although all five of the fractions extracted from green tea extract with different organic solvents had significant suppressive effects, the caffeine-containing fraction exhibited the strongest effect, suggesting that the protective effect of green tea against LPS + GaIN-induced liver injury is attributable mainly to caffeine. Authentic caffeine also significantly suppressed LPS + GaIN-induced liver injury when added to the diet (2 g/kg) and fed to rats for 14 d. Dietary green tea suppressed LPS + GaIN-induced apoptosis of liver cells, as assessed by DNA fragmentation. However, dietary green tea did not suppress LPS-induced enhancement of plasma concentration of tumor necrosis factor (TNF)-α, the cytokine that is thought to play a pivotal role in the pathogenesis of LPS-induced liver injury, although it significantly suppressed plasma concentrations of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10 and interferon (IFN)-γ. TNF-α + GaIN-induced liver injury and apoptosis were also suppressed by dietary green tea. In contrast, dietary caffeine significantly suppressed LPS-induced enhancement not only of plasma IL-1β, IL-6, IL-10 and IFN-γ concentrations, but also of TNF-α concentration. The results suggest that green tea might suppress LPS + GaIN-induced liver injury mainly through the inhibition of TNF-α-induced apoptosis of hepatocytes, rather than through the suppression of TNF-α production, although the suppressed production of TNF-α may be associated with the hepatoprotective effect of caffeine.