Lipid peroxidation and cell viability in isolated hepatocytes in a redesigned oxystat system: evaluation of the hypothesis that lipid peroxidation, preferentially induced at low oxygen partial pressures, is decisive for CCl4 liver cell injury.
An oxystat system is described which is capable of maintaining steady-state oxygen partial pressures (PO2) at levels between 0.1 and 300 mm Hg for hours or even days in incubations of respiring cells. The system was used to study effects of the hepatotoxin carbon tetrachloride (CCl4) on lipid peroxidation and cell viability in isolated hepatocytes from phenobarbital-pretreated rats at various steady-state PO2. At PO2 below 35 mm Hg, with a maximum effect at 7 mm Hg, CCl4 induced an immediate lipid peroxidation, the rate of which slowed down during further incubation. AT PO2 between 35 and 70 mm Hg, CCl4 initially induced only slight lipid peroxidation, while there was a significant increase in lipid peroxidation after approximately 30 min. At PO2 above 100 mm Hg, no lipid peroxidation was induced by CCl4. At PO2 of 70 mm Hg and below, with the maximum effect at 3 mm Hg, CCl4 also induced marked losses of cell viability. Under anaerobic conditions and at PO2 greater than 70 mm Hg, CCl4 was without effect on the viability of the liver cells. Cells isolated from the pericentral area of the liver lobule showed more lipid peroxidation and loss of cell viability than cells from the periportal area of the lobule. These results provide further evidence for the decisive role of lipid peroxidation, preferentially induced at low PO2, in CCl4 liver injury.
De Groot
H
H
Institut für Physiologische Chemie I, Universität Düsseldorf, West Germany.
Littauer
A
A
Hugo-Wissemann
D
D
Wissemann
P
P
Noll
T
T
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002470:Cell Survival; D056486:Chemical and Drug Induced Liver Injury; D066298:In Vitro Techniques; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D010313:Partial Pressure; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D010100:Oxygen