Effect of dietary fat on the in vitro hepatotoxicity of paracetamol.
In the present study, we have examined the effect of dietary fat on paracetamol-induced liver injury in an in vitro rat liver slice model. Rats were fed, for 7-10 days, diets containing either butter or polyunsaturated vegetable margarine, two fat sources commonly consumed in the human diet. Liver slices were then exposed to paracetamol for 2 hr and further incubated for 4 hr without paracetamol. Cell damage in the slices was quantified at 6 hr by measuring leakage of lactate dehydrogenase, increase in water content and potassium loss. Covalent binding of radioactive paracetamol to liver and the membrane fatty acid composition of the liver were also measured. Liver slices from rats fed butter diets were significantly more sensitive to the toxic effects of paracetamol than those from margarine fed rats. The membrane lipid composition of the livers also reflected the differing fatty acid content of the two diets.
McDanell
R E
RE
Department of Medicine, Rayne Institute, University College London, U.K.
Beales
D
D
Henderson
L
L
Sethi
J K
JK
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011188:Potassium / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014867:Water / Q000032:analysis
D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D014867:Water; D000082:Acetaminophen; D007770:L-Lactate Dehydrogenase; D011188:Potassium