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Eur J Gastroenterol Hepatol ; 15(9): 951-7, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12923366

ABSTRACT

OBJECTIVE: Thalidomide has anti-inflammatory, anti-tumour necrosis factor-alpha and anti-collagen activities. Cirrhosis is characterized by inflammation and fibrosis. Thus, thalidomide was evaluated in an experimental model of liver cirrhosis. METHODS: Male Wistar rats were used. Group 1 (n = 8) received mineral oil i.p. (control); group 2 (n = 15) received CCl(4) i.p. for 8 weeks to induce cirrhosis; group 3 (n = 15) consisted of rats receiving CCl(4) plus thalidomide (200 mg/kg/12 h); animals in group 4 (n = 8) received thalidomide only. Alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gamma-GTP) and alkaline phosphatase (ALP) were measured in serum, while collagen (hydroxyproline), glycogen and lipid peroxidation were determined in liver samples. A liver histopathological analysis was performed by using Gomori's trichromic staining. RESULTS: Intoxication with CCl(4) induced 33.3% mortality, while thalidomide co-treatment reduced it to 13.3%. The serum activities of ALT, gamma-GTP and ALP increased 3, 2 and 4-fold by CCl(4) treatment; thalidomide completely prevented elevation of these enzymes. In the liver, lipid peroxidation increased about 20-fold and glycogen was abolished in CCl(4) cirrhotic rats; thalidomide completely prevented the former and partially (P < 0.05) the latter. CCl(4) treated rats revealed a loss of normal architecture and nodules of hepatocytes surrounded by thick bands of collagen. Thalidomide + CCl(4) treated rats showed minor histological alterations and thinner bands of collagen. The anti-fibrotic effect estimated by hydroxyproline was partial but significant (P < 0.05). CONCLUSION: Thalidomide prevented necrosis, cholestasis and fibrosis induced by CCl(4). Its mechanism of action may be related to its anti-inflammatory, anti-tumour necrosis factor-alpha and anti-fibrotic activities reported previously.


Subject(s)
Immunosuppressive Agents/therapeutic use , Liver Cirrhosis, Experimental/prevention & control , Thalidomide/therapeutic use , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Carbon Tetrachloride , Drug Evaluation, Preclinical , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/enzymology , Liver Cirrhosis, Experimental/pathology , Male , Rats , Rats, Wistar , Survival Analysis , gamma-Glutamyltransferase/blood
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