Cell protection by fructose is independent of adenosine triphosphate (ATP) levels in paracetamol injury to rat liver slices.
Fructose protects cells against several types of injury but the mechanism of protection is uncertain. We have used paracetamol injury in rat liver slices as a model system to investigate the role of ATP levels in protection by fructose. Fructose depletes ATP levels in a concentration-dependent fashion in liver slices obtained from non-induced rats. Liver slices recover their ATP levels in the presence of fructose concentrations up to 10 mM. However, in the presence of of 20mM fructose, ATP levels are depleted for the duration of 240 min incubation. Adenine at 100 microM reverses the ATP depletion induced by 20 mM fructose in slices over 240 min incubation. Liver slices obtained from phenobarbitone induced rats were exposed to 10 mM paracetamol for 120 min and, then, incubated without paracetamol, with or without fructose for another 240 min. Introduction of 10 mM or 20 mM fructose in the second stage of incubation prevents paracetamol-induced injury. Fructose at 20 mM induces a rapid and marked depletion in slice ATP levels and these remain low throughout the second 240 min incubation period. Fructose at 10 mM maintains high ATP levels, even in paracetamol-treated slices. There is a profound protective effect against paracetamol-induced injury by either concentration. This suggests that protection is not dependent on high or on low ATP levels. Incubation of paracetamol-treated slices in the presence of 20 mM fructose plus 100 microM adenine in the second 240 min incubation period still results in the same level of protection as with 20 or 10 mM fructose along while reversing the ATP depletion observed with 20 mM fructose.
Martin
F L
FL
Department of Medicine, University College London, UK.
McLean
A E
AE
D000082:Acetaminophen / Q000633:toxicity*; D000225:Adenine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008867:Microtomy; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D005632:Fructose; D000082:Acetaminophen; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000225:Adenine