Increased
norepinephrine production by acute urine retention (AUR) induced sympathetic activation may contribute to acute liver injury (ALI) via the action of hepatic vasoconstriction and increased
reactive oxygen species (ROS) production. We evaluated whether
In-Chern-Hau-Tang, a hepatoprotective herb medicine, and its major ingredient
genipin, may ameliorate
norepinephrine-induced liver injury in the rat. We determined the effects of
In-Chern-Hau-Tang and
genipin on
norepinephrine-induced oxidative stress in the Kupffer and endothelial cells and AUR-induced ALI in the rat via a chemiluminescence analyzer, physiologic and biochemical determination and western blot. The results of in vitro study showed that
genipin with efficient H(2)O(2) and HOCl scavenging activities decreased
norepinephrine-enhanced ROS production in the Kupffer cell and endothelial cell cultures. AUR activated hepatic sympathetic nervous activity lead to a hepatic
hypoxia/hypoperfusion, and a reduction in bile flow. AUR increased intercellular adhesion molecular 1 (ICAM-1)
protein expression, and hepatic ROS production from the activated leukocyte
NADPH oxidase activity subsequently leading to plasma
aspartate aminotransferase (AST) elevation. Hepatic
sympathetic denervation, or oral pretreatment of
In-Chern-Hau-Tang or
genipin for 1 week ameliorated the level in AUR-induced hepatic
hypoxia/hypoperfusion, and bile stasis. Hepatic
denervation, In-Chern-Hau-Yang and
genipin inhibited AUR-enhanced hepatic
ICAM-1 expression, hepatic ROS production, leukocyte
NADPH oxidase activity and plasma AST activity. In conclusion,
In-Chern-Hau-Tang along with its active component,
genipin, can ameliorate AUR-induced ALI via the alleviation of oxidative stress possibly by the inhibition of sympathetic induced
hypoxia/hypoperfusion and leukocyte
NADPH oxidase activity.