Abstract
We investigated whether rat livers with obstructive jaundice produced with bile duct ligation (BDL) for 2 weeks are more vulnerable to stress of lipopolysaccharide (LPS) than those with sham operation ; f uthermore, we examined the effects of N-acetylcysteine (NAC) on LPS stimulation in rats with BDL. Results of serum concentration of a glutathione-S-transferase showed that LPS stimulation induces more severe hepatocellular injury in cholestatic rats more than in the sham rats. In addition, LPS stimulation aggravated mitochondrial function in the cholestatic rats than in the sham rats, as shown by the results of the mitochondrial reduced and oxidized glutathione pool and the hepatic adenosine triphosphate concentration. Intraperitoneal administration of NAC for 2 weeks improved mitochondrial function and hepatocellular injury. However, oxidative stress of polymorphonuclear leukocytes (PMNLs) infiltrating the hepatic tissue increased by NAC administration. The present results indicate that the cholestatic liver is vulnerable to the stress of LPS, NAC administration suppresses stress of LPS in the cholestatic liver, and that oxidative stress of PMNLs is not involved in mitochondrial dysfunction and hepatocellular injury in the cholestatic liver.
