Hi, I'm working with acute liver failure for 7 years, but now I'm interested in a model of subacute liver failure in mice induced by acetaminophen. However I didn't found any paper in PubMed. Does anyone have a model for this?
Dear André,
A reduced dosis of paracetamol will be necessary to obtain a subacute hepatitis. Andrea Pons works with 500mg/kg, however, the variability among paracetamol sources. In my opinion you should evaluate different dosis in mice.
Regards
Marcelo
Dear Andre,
Subacute liver failure models are scarce in the literature because they are hard to establish and to evaluate. For example, ALT levels present a lot of variation when using smaller doses of acetaminophen, because the number of injured and not injured mice fluctuates a lot. The same variability will impair histology and liver inflammation assessments.
I suggest you perform a dose-response curve and choose the smallest dose capable of inducing 1000 U/L of ALT in the serum, which will probably be 300-400mg/kg in fasted C57BL/6 mice. On the other hand, you may try several low-dose (200-300mg/kg) acetaminophen administrations to mice (along a week) and see their phenotype.
Good luck
Pedro
Dear Marcelo And Pedro,
thanks for the reply. I have now a nice idea where to start. I was looking for this subacute models, since I'll start to study the effects of suplementary dietary on liver during acetaminphen administrations.
Warm regards
Andre