Hypothyroidism protects rat liver from acetaminophen hepatotoxicity

Citation
R. Bruck et al., Hypothyroidism protects rat liver from acetaminophen hepatotoxicity, DIG DIS SCI, 44(6), 1999, pp. 1228-1235
Citations number
33
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
DIGESTIVE DISEASES AND SCIENCES
ISSN journal
01632116 → ACNP
Volume
44
Issue
6
Year of publication
1999
Pages
1228 - 1235
Database
ISI
SICI code
0163-2116(199906)44:6<1228:HPRLFA>2.0.ZU;2-G
Abstract
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.