Paracetamol toxicity and its prevention by cytoprotection with iloprost

Abstract

In a well-established two phase model of paracetamol toxicity in hamster hepatocytes cell death was accompanied, but not preceded, by a rise in cytosolic free calcium [Ca 2+] i. Cell death appears to involve reversible oxidative damage, possibly to the cytoskeleton or mitochondria. In this model low concentrations (10 −8 to 10 −14 M) of iloprost, a stable analogue of prostacyclin, offered protection against the toxic effects of paracetamol. In preliminary studies with a rat liver epithelial cell line transduced with murine P4501A2 the toxicity of paracetamol was attenuated by iloprost. Inhibition of protein synthesis with cycloheximide had no effect on paracetamol toxicity but abolished the cytoprotective effect of iloprost.