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.
Biasi
F
F
Department of Experimental Medicine and Oncology, University of Turin, Italy.
Albano
E
E
Chiarpotto
E
E
Corongiu
F P
FP
Pronzato
M A
MA
Marinari
U M
UM
Parola
M
M
Dianzani
M U
MU
Poli
G
G
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