Enhanced lipid peroxidation in hepatic cirrhosis.
BACKGROUND
Lipid peroxidation is thought to play a role in the evolution of liver damage, based on evidence in experimental models. However, evidence that lipid peroxidation occurs in patients with liver disease remains to be provided. We addressed the hypothesis by measuring levels of 8-epi Prostaglandin F2 alpha a bioactive prostaglandin isomer produced by free radical catalyzed peroxidation of arachidonic acid, in patients with liver cirrhosis.


METHODS
In 42 patients with hepatic cirrhosis 8-epi Prostaglandin F2 alpha, factor VII activity, endotoxemia, carotenoids and alpha-tocopherol were measured. In 10 patients 8-epi Prostaglandin F2 alpha was also measured before and 30 days after 300 mg b.i.d. vitamin E administration.


RESULTS
Cirrhotic patients had significant higher 8-epi Prostaglandin F2 alpha, excretion than controls [median (range): 199.2 (60.0-812) vs 85.9 (55.6-160.0) pg/mg creatinine, p < 0.0001]. Patients with urinary 8-epi Prostaglandin F2 alpha above the range in controls were more likely to have moderate or severe than mild liver failure (p < 0.004). They also had lower factor VII activity (62 +/- 19 vs 74 +/- 15%, P < 0.02) than patients with normal levels of the isoprostane. Urinary excretion of 8-epi Prostaglandin F2 alpha correlated directly with endotoxemia (Rho = 0.56, p < 0.0002) and inversely with factor VII (Rho = -0.39, p < 0.02). Cirrhotic patients given vitamin E showed a significant decrease of urinary 8-epi Prostaglandin F 2 alpha [median (range): 342.5 (170 - 812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04].


CONCLUSIONS
This study demonstrated that lipid peroxidation is increased in vivo in patients with cirrhosis and suggests that oxidant stress might contribute to the deterioration of liver disease.
Pratico
D
D
Istituto di Clinica Medica I, University La Sapienza, Rome, Italy.
Iuliano
L
L
Basili
S
S
Ferro
D
D
Camastra
C
C
Cordova
C
C
FitzGerald
G A
GA
Violi
F
F
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D016022:Case-Control Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D028441:F2-Isoprostanes; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D028441:F2-Isoprostanes; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost