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Hypothyroidism Protects Rat Liver from Acetaminophen Hepatotoxicity

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Abstract

Recent data from animal studies suggest thatinduced hypothyroidism inhibits the development of liverinjury in several animal models, including livercirrhosis and fulminant hepatic failure in rats, and immune-mediated acute liver injury in mice. Theaim of the present study was to determine whetherhypothyroidism would likewise preventacetaminophen-induced hepatic damage in rats. Liverdamage was induced by acetaminophen (2 g/kg) administered bygavage to fasting rats as a single dose. Hypothyroidismwas induced by methimazole, propylthiouracil, orsurgical thyroidectomy and confirmed by elevated serum levels of TSH. Hypothyroidism significantlyinhibited acetaminophen-induced liver damage asmanifested by the decreased serum levels of liverenzymes, malondialdehyde and blood ammonia, as well asby the higher hepatic glutathione content, in allthree groups of hypothyroid rats compared to euthyroidcontrols (P < 0.01). Histopathologic analysis showedsignificantly less liver necrosis and inflammation in the acetaminophen-treated hypothyroid rats.Oxygen extraction, measured in isolated perfused ratliver preparation, was also reduced in the hypothyroidlivers to 42 ± 8% compared to 81 ± 14% ofcontrols (P < 0.01). However, the expression ofCYP2E1 in the livers of hypothyroid rats, as measured bywestern blot analysis, was not decreased compared tocontrol rats. These results suggest that inducedhypothyroidism, regardless of the mode of induction, protectsrat liver from acetaminophen hepatotoxicity. This effectmay be related to hypometabolism of liver cells, but theexact mechanism needs further clarification.

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Authors
  1. Rafael Bruck
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  2. Daniela Frenkel
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  3. Haim Shirin
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  4. Hussein Aeed
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  5. Zipora Matas
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  6. Moshe Papa
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  7. Liliana Zaidel
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  8. Yona Avni
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  9. Ran Oren
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  10. Zamir Halpern
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Bruck, R., Frenkel, D., Shirin, H. et al. Hypothyroidism Protects Rat Liver from Acetaminophen Hepatotoxicity. Dig Dis Sci 44, 1228–1235 (1999). https://doi.org/10.1023/A:1026652913347

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  • DOI: https://doi.org/10.1023/A:1026652913347

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