During thioacetamide-induced acute liver failure, the proliferative response of hepatocytes to thyroid hormone is maintained, indicating a potential therapeutic approach to toxin-induced liver disease.
In toxic liver injury, proliferation of preexisting hepatocytes helps restore liver mass and function. While loss of liver mass per se stimulates hepatocyte proliferation, exogenous mitogens have a potential role in enhancing liver regeneration. The aim of this study was to characterize the effects of the mitogen, tri-iodothyonine, on the regenerative capacity of hepatocytes during thioacetamide-induced liver failure. Rats received (two) thioacetamide injections and, 12 hr later, either tri-iodothyonine or vehicle-only control. Liver cell proliferation was assessed and comparison made with other control groups receiving tri-iodothyonine or vehicle only. In rats with thioacetamide-induced hepatitis the proportion of hepatocytes in S-phase was greater in the tri-iodothyonine group (27+/-3.5%) compared to the vehicle-only group (20+/-2.5%; P < 0.05), with, notably, a greater number of midzonal (BrdU) positive hepatocytes in the tri-iodothyonine group. We conclude that the ability of hepatocytes in the midzonal areas of rat liver to proliferate in response to tri-iodothyonine is maintained during severe acute toxic injury.
Malik
Raza
R
Centre for Hepatology, Department of Medicine, Royal Free Campus, Royal Free and University College Medical School, Rowland Hill Street, Hampstead, London, United Kingdom, NW3 2PF. r.malik@medsch.ucl.ac.uk
Saich
Rebecca
R
Rahman
Tony
T
Hodgson
Humphrey
H
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology*; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D013853:Thioacetamide; D014284:Triiodothyronine / Q000494:pharmacology*
D008934:Mitogens; D014284:Triiodothyronine; D013853:Thioacetamide