Thalidomide ameliorates carbon tetrachloride induced cirrhosis in the rat

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 CCl4 i.p. for 8 weeks to induce cirrhosis; group 3 (n=15) consisted of rats receiving CCl4 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 CCl4 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 CCl4 treatment; thalidomide completely prevented elevation of these enzymes. In the liver, lipid peroxidation increased about 20-fold and glycogen was abolished in CCl4 cirrhotic rats; thalidomide completely prevented the former and partially (P<0.05) the latter. CCl4 treated rats revealed a loss of normal architecture and nodules of hepatocytes surrounded by thick bands of collagen. Thalidomide + CCl4 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 CCl4. Its mechanism of action may be related to its anti-inflammatory, anti-tumour necrosis factor-alpha and anti-fibrotic activities reported previously. (C) 2003 Lippincott Williams Wilkins.