Lipid peroxidation as molecular mechanism of liver cell injury during reperfusion after ischemia

doi:10.1016/0891-5849(94)90191-0

Free Radical Biology and Medicine

Volume 16, Issue 6, June 1994, Pages 763-770

https://doi.org/10.1016/0891-5849(94)90191-0 Get rights and content

Abstract

The pathophysiological importance of reactive oxygen species has been extensively documented in the pathogenesis of hepatic ischema-reperfusion injury. Kupffer cells and neutrophils were identified as the dominant sources of the postischemic oxidant stress. To test the hypothesis that a direct free radical-mediated injury mechanism (lipid peroxidation; LPO) may be involved in the pathogenesis, highly sensitive and specific parameters of LPO, i.e., hydroxy-eicosatetraenoic acids (HETES), and F₂-isoprostanes, were determined by gas chromatographic-mass spectrometric analysis in liver tissue and plasma during 45 min of hepatic ischemia and up to 24 h of reperfusion. A significant 60–250% increase of F₂-isoprostane levels in plasma was found at all times during reperfusion; the HETE content increased only significantly at 1 h of reperfusion and in severely necrotic liver tissue at 24 h with increases between 90–320%. On the other hand, in a model of LPO-induced liver injury (infusion of 0.8 μmol tert-butylhydroperoxide/min/g liver), the hepatic HETE content increased two to fourfold over baseline values at 45 min, i.e., before liver injury. A further increase to 12- to 30-fold of baseline was observed during moderate liver injury. Based on these quantitative comparisons of LPO and liver injury, it seems highly unlikely that LPO is the primary mechanism of parenchymal cell injury during reperfusion, although it cannot be excluded that LPO may be important as a damaging mechanism in a limited compartment of the liver, e.g., endothelial cells, close to the sources of reactive oxygen, e.g., Kupffer cells and neutrophils.

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Original contributionLipid peroxidation as molecular mechanism of liver cell injury during reperfusion after ischemia

Abstract

Chem. Biol. Interact.

Free Radic. Biol. Med.

Arch. Biochem. Biophys.

J. Surg. Res.

Free Radic. Biol. Med.

J. Surg. Res.

Clin. Biochem.

Biochem. Pharmacol.

Anal. Biochem.

Biochem. Pharmacol.

Chem. Biol. Interact.

Biochem. Pharmacol.

Anal. Biochem.

Anal. Biochem.

Prostaglandins, Leukotr. Essent. Fatty Acids

Arch. Biochem. Biophys.

Biochem. Biophys. Res. Commun.

FEBS Lett.

Chem. Biol. Interact.

Reactive oxygen species during ischemia-reflow injury in isolated perfused rat liver

J. Clin. Invest.

Oxidant stress during reperfusion of ischemic liver: No evidence for a role of xanthine oxidase

Hepatology

Cytochemical studies of hydrogen peroxide generation in postischemic hepatocytes

Am. J. Physiol.

Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver

Am. J. Physiol.

Original contribution
Lipid peroxidation as molecular mechanism of liver cell injury during reperfusion after ischemia