Abstract | BACKGROUND/AIMS: METHODS:
Cirrhosis was induced in male Wistar rats by intraperitoneal (i.p.) administration of thioacetamide (200 mg/kg twice weekly for 12 weeks). In the treated group, the Ras antagonist FTS (5 mg/kg, i.p./3 times/week) was administered for 8 weeks after liver cirrhosis has already been established. Control cirrhotic rats received PBS injections for 8 weeks. RESULTS: Rats treated with FTS for 8 weeks had lower histopathologic score of fibrosis (P = 0.01), lower hepatic hydroxyproline levels (P = 0.0002) and lower spleen weight (P = 0.02) than the cirrhotic rats treated with PBS. Following FTS treatment, the MMP-2 and MMP-9-induced collagenolytic activity and TIMP-2 expression, were increased in FTS-compared to PBS-treated rats. TUNEL assay of liver sections performed 8 weeks after thioacetamide withdrawal showed increased apoptotic figures in both groups (P = NS). CONCLUSIONS: These results indicate that the Ras antagonist FTS accelerates the regression of experimentally-induced hepatic cirrhosis. The mechanism may involve increased collagenolytic activity.
|
Authors | Shimon Reif, Hussein Aeed, Yael Shilo, Reuven Reich, Yoel Kloog, Young Oh Kweon, Rafael Bruck |
Journal | Journal of hepatology
(J Hepatol)
Vol. 41
Issue 2
Pg. 235-41
(Aug 2004)
ISSN: 0168-8278 [Print] Netherlands |
PMID | 15288472
(Publication Type: Journal Article)
|
Chemical References |
- Salicylates
- farnesylthiosalicylic acid
- Thioacetamide
- Tissue Inhibitor of Metalloproteinase-2
- Farnesol
- Metalloproteases
- Hydroxyproline
|
Topics |
- Animals
- Apoptosis
- Farnesol
(analogs & derivatives, pharmacology)
- Gene Expression
(drug effects)
- Genes, ras
- Hydroxyproline
(metabolism)
- In Situ Nick-End Labeling
- Liver
(drug effects, metabolism, pathology, physiopathology)
- Liver Cirrhosis, Experimental
(chemically induced, genetics, pathology, physiopathology)
- Male
- Metalloproteases
(metabolism)
- Organ Size
(drug effects)
- Rats
- Rats, Wistar
- Salicylates
(pharmacology)
- Spleen
(pathology)
- Thioacetamide
- Tissue Inhibitor of Metalloproteinase-2
(metabolism)
|