Thalidomide salvages lethal hepatic necroinflammation and accelerates recovery from cirrhosis in rats.
OBJECTIVE
The authors investigated the feasibility of thalidomide employed to treat liver fibrosis.


METHODS
A cirrhotic model was established using Sprague-Dawley rats fed thioacetamide. Thalidomide-treated group was given thalidomide (10mg/kg/day) intraperitoneally for 10 consecutive days. Mortality, histopathological changes, TNFalpha, TGFbeta1, TIMP-1 and TIMP-2 were determined. Expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from the experimental rats were determined.


RESULTS
The mortality rates of thalidomide-treated group and vehicle-treated group were 8 and 32%, respectively. The total Knodell score of thalidomide-treated rats was lower than those of vehicle-treated rats. Micro-nodular cirrhosis resolved grossly in thalidomide-treated rats on day 28; while vehicle-treated rats continued to display uneven liver surface on day 28. Expression of TNFalpha, TGFbeta1, TIMP-1, and TIMP-2 was decreased in thalidomide-treated rats compared to those treated with vehicles. Finally, the expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from rats treated with thalidomide were much lower than those treated with vehicle.


CONCLUSIONS
Thalidomide salvages lethal hepatic necroinflammation, accelerates recovery from cirrhosis in rats, and works by suppressing of TNFalpha and TGFbeta1 production of Kupffer's cells.
Yeh
Ta-Sen
TS
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. surglab@adm.cgmh.org.tw
Ho
Yu-Pin
YP
Huang
Shiu-Feng
SF
Yeh
Jun-Nan
JN
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D000818:Animals; D017364:Collagenases / Q000378:metabolism; D006505:Hepatitis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016879:Salvage Therapy; D013792:Thalidomide / Q000627:therapeutic use*; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C508962:Tgfb1 protein, rat; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat