Age-related toxicity of paracetamol in mouse hepatocytes

Hepatocytes from postnatal and adult mice were isolated by perfusion of the liver with a collagenase-containing bicarbonate buffer. These were allowed to attach to collagen-coated tissue culture dishes and were then examined for their susceptibility to paracetamol toxicity. After an 8 hr incubation in either 0.1 or 1.0 mM paracetamol, the extent of lactate dehydrogenase leakage and depletion of glutathione were similar in hepatocytes from young (1-, 2- and 3-week-old) mice when compared to adult mice. The covalent binding of [14C]-paracetamol to protein was greater in the hepatocytes from young mice. The results indicate that while the amount of reactive metabolites free to react with cellular constituents is greater in hepatocytes from young mice, the amount of damage produced was not different than that found in those from adults.