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The influenceof exogenous leukotrienes and lipoxygenase inhibitors on apoptosis and necrosisin rat cultured hepatocytes.
G.N. Korniychuk N.V. Makogon I.N. Alexeyeva I.V. Lushnikova
A.A. Bogomoletz Institute of Physiology
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Abstract
Liver cell death by apoptosis and necrosis occurs upon
the liver injury. Lipoxygenase pathway of arachidonic
acid metabolism is known to regulate the viability
and apoptosis in some cell types, but its role in
hepatocyte cell death is not fully understood. We
studied the influence of leukotrienes (LT) and lipoxygenase
inhibitors on apoptosis and necrosis in
rat hepatocyte primary culture by double staining with
Hoechst 33342 and propidium iodide and electron
microscopy. Treatment with general lipoxygenase inhibitor
nordihydoguaiaretic acid and 5-lipoxygenase
inhibitor сaffeic acid (2 . 10 -5M) for 4 and 24 h indu-
ced hepatocyte apoptosis. LTB4 and LTC4 (10 -8M)
decreased the number of living cells and increased the
number of necrotic cells. LTs exerted the same necrotic
effect on hepatocytes, treated with lipoxygenase inhi-
bitors. It is important that LTs decreased apoptosis
induced by inhibitors treatment. These data suggest
that lipoxygenase pathway of arachidonic acid meta-
bolism is important regulator of hepatocytes viability
and apoptosis The increase of lipoxygenase product
formation, in particular LTs, may diminish apoptosis
and increase necrosis in hepatocytes upon the liver
injury.
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