Methimazole alleviates hepatic encephalopathy in bile-duct ligated cirrhotic rats.
BACKGROUND
Acute or chronic liver damage may lead to hepatic encephalopathy. Previous studies have indicated the hemodynamic and hormonal mimicry between portal hypertension and hyperthyroidism. Furthermore, medically or surgically induced hypothyroidism has been found to be beneficial in ameliorating hyperdynamic circulation in the portal hypertensive state and in alleviating acute or chronic liver injury in rats. However, the effect of chronic thyroid hormone inhibition on chronic hepatic encephalopathy in cirrhosis remains unknown.


METHODS
Liver cirrhosis was induced by bile-duct ligation (BDL) in male Sprague-Dawley rats. Three weeks after BDL, rats were randomized to receive either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At the end of 6 weeks after BDL, severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters were measured. Blood samples were collected for determination of thyroid stimulating hormone, ammonia and liver biochemistry.


RESULTS
The heart rate of the methimazole-treated group was significantly lower than that of the control group (p = 0.015), whereas there were no differences in the mean arterial pressure and portal pressure. The total amount of movements were significantly increased in the methimazole group (p = 0.029). Plasma levels of ammonia, aspartate aminotransferase and alkaline phosphatase were significantly lower (p = 0.01) and thyroid stimulating hormone significantly higher (p = 0.035) in the methimazole group.


CONCLUSIONS
Chronic methimazole treatment alleviates hepatic encephalopathy and liver damage in rats with BDL-induced hepatic cirrhosis.
Chang
Ching-Chih
CC
Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan, R.O.C.
Chen
Yi-Chou
YC
Huang
Hui-Chun
HC
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Chan
Cho-Yu
CY
Wang
Sun-Sang
SS
Lee
Shou-Dong
SD
D000410:Alanine Transaminase / Q000097:blood; D000641:Ammonia / Q000097:blood; D000818:Animals; D013956:Antithyroid Agents / Q000627:therapeutic use*; D001652:Bile Ducts; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006501:Hepatic Encephalopathy / Q000188:drug therapy*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000150:complications; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013972:Thyrotropin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D013956:Antithyroid Agents; D014409:Tumor Necrosis Factor-alpha; D008713:Methimazole; D000641:Ammonia; D013972:Thyrotropin; D000410:Alanine Transaminase