Enhanced Lipid Peroxidation in Hepatic Cirrhosis

Abstract

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 F₂α, 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 F₂α, factor VII activity, endotoxemia, carotenoids and α-tocopherol were measured. In 10 patients 8-epi Prostaglandin F₂α was also measured before and 30 days after 300 mg b.i.d. vitamin E administration.

Results

Cirrhotic patients had significantly higher 8-epi Prostaglandin F₂α 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 F₂α 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 F₂α 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 F₂α [median (range): 342.5 (170-812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04].

Conclusion

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.