Prevention of paracetamol-induced liver injury by fructose.
Hepatic cell injury was studied in an in vitro system using rat liver slices incubated in two stages. During the first 2 hr slices were exposed to 10 mM paracetamol, this was absent during the subsequent 4 hr of incubation. Cell damage was quantified at the end by measuring leakage of lactic dehydrogenase, increase in water content and potassium loss. Treatment of slices with 20 mM fructose in the second period of incubation prevented paracetamol-induced damage. The effect of fructose was not modified by the continued presence of paracetamol in the second incubation period. The inhibition of glycolysis either with 1 mM NaF or 10 microM iodoacetate blocked the effect of fructose. The protective effect afforded by fructose was not duplicated by the addition of lactate. All these findings strongly suggest an increase in intracellular ATP levels as the most probable explanation for the protective effect of fructose, and point to fructose as a potentially useful therapeutic tool for protection of the liver late in paracetamol intoxication.
Mourelle
M
M
Department of Clinical Pharmacology, University College London, U.K.
Beales
D
D
McLean
A E
AE
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005001:Ethionine / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005632:Fructose; D000082:Acetaminophen; D007770:L-Lactate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D005001:Ethionine