Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat.
OBJECTIVE
Thromboxane levels correlate with severity of liver injury in rats given alcohol. The aim of this study was to evaluate the effect of thromboxane inhibitors on pathological changes in experimental alcoholic liver disease.


METHODS
Male Wistar rats were given a liquid diet and ethanol intragastrically for 1 month. The thromboxane inhibitors tested were a thromboxane receptor antagonist (TXRA) and a thromboxane synthase inhibitor (TXSI). Pathological changes, liver and plasma thromboxane levels, 6-ketoprostaglandin F1 alpha levels, lipid peroxidation, and messenger RNA levels for tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF) beta were evaluated.


RESULTS
Treatment with thromboxane inhibitors prevented necrosis and inflammation. In the TXSI-treated group, fatty liver was also decreased. Ethanol administration led to a 3-4-fold increase in liver thromboxane levels; a reduction in thromboxane levels and lipid peroxidation was seen in the TXSI group. In all treatment groups, TNF-alpha and TGF-beta messenger RNA levels were decreased.


CONCLUSIONS
The prevention of necroinflammatory changes in thromboxane-treated groups is related to a decrease in TNF-alpha levels. Inhibition of TGF-beta expression may also prevent fibrosis in ethanol-treated rats.
Nanji
A A
AA
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Khwaja
S
S
Rahemtulla
A
A
Miao
L
L
Zhao
S
S
Tahan
S R
SR
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D005235:Fatty Liver, Alcoholic / Q000097:blood / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000473:pathology; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000097:blood*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood*; D016211:Transforming Growth Factor alpha / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D010080:Oxazoles; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D013929:Thromboxane B2; D013928:Thromboxane A2; C078904:ifetroban