Monitoring of serum markers for fibrosis during CCl₄-induced liver damage. Effects of anti-fibrotic agents

Liver fibrosis was induced in rats by repeated peritoneal injections of carbon tetrachloride (CCl₄) over a period of 2-11 weeks. Serum procollagen III peptide (SPIIINP), prolidase (SP) and alanine aminotransferase (SALT) levels were monitored during the period of induction. The extent of fibrosis was semi-quantitatively estimated after collagen staining, and the anti-fibrotic effects of 16,16-dimethyl prostaglandin E₂ (DMPGE₂), colchicine, and zinc sulphate were studied. SPIIINP and SP were increased the first 2 weeks after CCl₄ administration and peaked at 6 weeks. Alterations in SPIIINP and SP correlated well to the semi-quantitative histological score of liver sections during the first 6 weeks, and SP was positively related to SPIIINP throughout the whole induction period. DMPGE₂ decreased SPIIINP, SP and SALT significantly in addition to a markedly decreased formation of liver collagens. Colchicine had a similar but less dramatic effect, whereas zinc sulphate only reduced SPIIINP without influencing liver damage. In conclusion SPIIINP seems to be a valuable indicator of liver fibrogenesis, and SP may play a limited role in indicating accelerated collagen metabolism in the liver. DMPGE₂ obviously inhibited the production of collagens induced by CCl₄. Colchicine also had an apparent effect on liver fibrosis, whereas zinc sulphate merely seemed to postpone it.