Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats.
OBJECTIVE
To study the effect of leflunomide on CCl4-induced hepatic fibrosis in rats.


METHODS
Hepatic fibrosis was induced by subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-beta1 (TGF-beta1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-kappaB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin.


RESULTS
Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-kappaB expression in liver tissue, and reduced elevated serum TGF-kappa1 and NO levels in rats of hepatic fibrosis.


CONCLUSIONS
Leflunomide showed inhibitory action on hepatic fibrosis induced by CCl4 in rats.
Yao
Hong-wei
HW
Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, School of Medicine, Zhejiang University, Hangzhou 310031, China. yhgwei@163.com
Li
Jun
J
Chen
Ji-qiang
JQ
Xu
Shu-yun
SY
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning; D024061:Collagen Type III / Q000097:blood; D006909:Hydroxyproline / Q000097:blood; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1
D000276:Adjuvants, Immunologic; D024061:Collagen Type III; D007555:Isoxazoles; D016328:NF-kappa B; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077339:Leflunomide; D006909:Hydroxyproline