In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride.
Isolated rat hepatocytes exposed to CCl4 showed a stimulated formation of malonaldehyde after only 30-60 min incubation. Conversely, the onset of hepatocyte death was a relatively late event, being significant only after 2-3 h of treatment. A cause-effect relationship between the two phenomena has been demonstrated by using hepatocytes isolated from rats pretreated with alpha-tocopherol. Comparable results were obtained in vivo where supplementation with alpha-tocopherol 15 h before CCl4 dosing induced a partial or complete protection against the drug's necrogenic effect, depending on the concentration of the haloalkane used. Moreover, the vitamin supplementation prevented the CCl4-induced increase of liver total calcium content, probably by blocking alterations in the liver cell plasma membranes due to lipid peroxidation.
Department of Experimental Medicine and Oncology, University of Turin, Italy.
F
F
Biasi
E
E
Albano
E
E
Chiarpotto
F P
FP
Corongiu
M A
MA
Pronzato
U M
UM
Marinari
M
M
Parola
M U
MU
Dianzani
G
G
Poli
D000818:Animals; D002122:Calcium Chloride / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology
D014810:Vitamin E; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D002122:Calcium Chloride