The effect of malotilate on type III and type IV collagen, laminin and fibronectin metabolism in dimethylnitrosamine-induced liver fibrosis in the rat.
OBJECTIVE
Dimethylnitrosamine-induced liver damage was used as an experimental model to study the effect of malotilate on liver fibrosis.


METHODS
Deposition of type III and IV collagens, laminin and fibronectin were studied from liver section by immunohistochemical techniques using specific antibodies. Serum concentrations of aminoterminal propeptide of type III procollagen, and aminoterminal and carboxyterminal domains of type IV collagen were determined by radioimmunoassays from both malotilate-treated and untreated animals with dimethylnitrosamine injury.


RESULTS
A significant elevation of all three serum parameters 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. Malotilate prevented increases in serum markers of type III and IV collagen synthesis as well as accumulation of the collagens, laminin and fibronectin in the liver.


CONCLUSIONS
The results suggest that serum marker determinations can be used to monitor changes in type III and IV collagen synthesis in the liver. The data indicate that malotilate has a preventive effect in dimethylnitrosamine-induced experimental hepatic fibrosis.
Department of Internal Medicine, University of Oulu, Finland.
L
L
Ryhanen
F
F
Stenback
L
L
Ala-Kokko
E R
ER
Savolainen
D000818:Animals; D000918:Antibody Specificity; D003094:Collagen / Q000378:metabolism*; D004128:Dimethylnitrosamine; D005069:Evaluation Studies as Topic; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008314:Malonates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005353:Fibronectins; D007797:Laminin; D008314:Malonates; D003094:Collagen; D004128:Dimethylnitrosamine; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate