Hypoxia potentiates killing of hepatocyte monolayers by leukotrienes, hydroperoxyeicosatetraenoic acids, or calcium ionophore A23187.
Potentiation of chemical toxicity by hypoxia was studied in confluent hepatocyte monolayers. Addition of either hydroperoxyarachidonic acid (50 micrograms), leukotriene C4 (10 micrograms), or calcium ionophore A23187 (1.8 micrograms) to hepatocyte monolayers followed by incubation in 2% oxygen for 24 h killed 95% of the hypoxic cells, but was without effect on the normoxic cells. The greater than 10-fold increase in toxicity of A23187 suggests that hypoxic cells are less able to regulate intracellular calcium. The increased toxicity of hydroperoxyarachidonic acid and leukotriene C4 may be due to a related reduction in activity of protective enzymes.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007975:Leukotriene B4 / Q000494:pharmacology; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology*; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000494:pharmacology*
D001095:Arachidonic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D013189:SRS-A; D007975:Leukotriene B4; D000001:Calcimycin; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D010100:Oxygen