Altered energy metabolism and oxidative injury following endotoxemia in rats with normal or cirrhotic livers.
The release of oxygen-derived free radicals has been implicated in endotoxin-mediated hepatic injury. The effect of hepatic lipid peroxidation on tissue energy reserves in the livers of normal and cirrhotic rats was studied following administration of E. coli endotoxin. Before endotoxin injection, the basal hepatic energy charge was lower and levels of hepatic malondialdehyde (MDA) and total glutathione (GSH) higher in cirrhotic rats than in normal rats. Virtually identical levels of blood endotoxin were obtained in the two groups 24 h after injection of LD50 doses of endotoxin (20 mg/kg and 1 mg/kg in normal and cirrhotic rats, respectively). Hepatic energy charge, tissue blood flow, GSH and glutathione peroxidase (GPX) were consistently or transiently decreased up to 24 h after the injection of endotoxin in both normal and cirrhotic rats. MDA, significantly increased in normal rats 1 h after injection of endotoxin, returned to normal levels 3-12 h after endotoxin administration, but was again elevated at 24 h. Cirrhotic rats did not show any significant change in MDA following endotoxin injection. In normal rats, endotoxin appears to trigger the liberation of free radicals accelerating depletion of hepatic energy reserves, over and above the effect of decreased hepatic blood flow. In contrast, increased lipid peroxidation was not detected in cirrhotic rats despite GSH and GPX consumption during endotoxemia (indicating oxygen radical generation). Cirrhotic livers were apparently protected against oxygen radical injury by higher levels of endogenous GSH and GPX. Reduced hepatic blood flow may be mainly responsible for the alteration in energy metabolism of the cirrhotic liver.
First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
K
K
Ouchi
J
J
Tanabe
T
T
Tominaga
K
K
Ito
S
S
Saijo
S
S
Matsuno
D000818:Animals; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014115:Toxemia / Q000378:metabolism*
D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D005978:Glutathione