Recent data from animal studies suggest that induced hypothyroidism inhibit
s the development of liver injury in several animal models, including liver
cirrhosis and fulminant hepatic failure in rats, and immune-mediated acute
liver injury in mice. The aim of the present study was to determine whethe
r hypothyroidism would likewise prevent acetaminophen-induced hepatic damag
e in rats. Liver damage was induced by acetaminophen (2 g/kg) administered
by gavage to fasting rats as a single dose. Hypothyroidism was induced by m
ethimazole, propylthiouracil, or surgical thyroidectomy and confirmed by el
evated serum levels of TSH, Hypothyroidism significantly inhibited acetamin
ophen-induced liver damage as manifested by the decreased serum levels of l
iver enzymes, malondialdehyde and blood ammonia, as well as by the higher h
epatic glutathione content, in all three groups of hypothyroid rats compare
d to euthyroid controls (P < 0.01). Histopathologic analysis showed signifi
cantly less liver necrosis and inflammation in the acetaminophen-treated hy
pothyroid rats. Oxygen extraction, measured in isolated perfused rat liver
preparation, was also reduced in the hypothyroid livers to 42 +/- 8% compar
ed to 81 +/- 14% of controls (P < 0.01). However, the expression of CYP2E1
in the livers of hypothyroid rats, as measured by western blot analysis, wa
s not decreased compared to control rats. These results suggest that induce
d hypothyroidism, regardless of the mode of induction, protects rat liver f
rom acetaminophen hepatotoxicity. This effect may be related to hypometabol
ism of liver cells, but the exact mechanism needs further clarification.