THE EFFECT OF MALOTILATE ON TYPE-III AND TYPE-IV COLLAGEN, LAMININ AND FIBRONECTIN METABOLISM IN DIMETHYLNITROSAMINE-INDUCED LIVER FIBROSISIN THE RAT

Background/Aims: Dimethylnitrosamine-induced liver damage was used as an experimental model to study the effect of malotilate on liver fibro sis. Methods: Deposition of type III and IV collagens, laminin and fib ronectin were studied from liver section by immunohistochemical techni ques using specific antibodies. Serum concentrations of aminoterminal propeptide of type III procollagen, and aminoterminal and carboxytermi nal domains of type IV collagen were determined by radioimmunoassays f rom both malotilate-treated and untreated animals with dimethylnitrosa mine injury. Results: A significant elevation of all three serum param eters was observed after 3 weeks of hepatic injury in animals without malotilate treatment, and a constant increase was noted in the amounts of hepatic type III and IV collagens, laminin and fibronectin. Maloti late prevented increases in serum markers of type III and IV collagen synthesis as well as accumulation of the collagens, laminin and fibron ectin in the liver. Conclusions: The results suggest that serum marker determinations can be used to monitor changes in type III and IV coll agen synthesis in the liver. The data indicate that malotilate has a p reventive effect in dimethylnitrosamine-induced experimental hepatic f ibrosis.