Preventive effect of malotilate on carbon tetrachloride-induced liver damage and collagen accumulation in the rat.
Malotilate is a new drug suggested for use in chronic liver diseases. It is shown here to prevent liver damage caused by CCl4. The concomitant administration of malotilate with CCl4 significantly decreased hydroxyproline accumulation in the liver, liver prolyl 4-hydroxylase and liver and serum galactosylhydroxylysyl glucosyltransferase activities. However, it had no effect on the daily urinary hydroxyproline excretion or the hydroxyproline content of the skin, liver or lungs in normal young growing rats. It also had no specific inhibitory effect on hydroxyproline synthesis or secretion in fibroblast cultures, and did not affect the amount of procollagen-alpha 1(I)-specific mRNAs in these cultures. Thus it seems to have no direct inhibitory effect on collagen metabolism. In addition to inhibition of liver collagen accumulation, malotilate was also able to prevent the development of morphological changes in the liver such as focal necrosis, fatty infiltration and inflammatory changes. It also normalized almost completely the standard liver-function tests. It is possible that malotilate may prevent excessive collagen deposition by inhibiting the inflammation caused by CCl4-induced liver damage.
Ala-Kokko
L
L
Collagen Research Unit, Biocenter, Oulu, Finland.
Stenbäck
F
F
Ryhänen
L
L
D000818:Animals; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005964:Glucosyltransferases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000517:prevention & control*; D008314:Malonates / Q000627:therapeutic use*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008314:Malonates; D003094:Collagen; D002251:Carbon Tetrachloride; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase; D005964:Glucosyltransferases; C023247:UDP glucose-collagen glucosyltransferase; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate