Preventive effect of malotilate on dimethylnitrosamine-induced liver fibrosis in the rat.
Dimethylnitrosamine-induced liver damage, which leads to hepatic failure and death of the animal, was prevented by treatment with malotilate. The accumulation of collagen and the morphologic changes caused by dimethylnitrosamine, such as inflammatory cell accumulation and fibrosis, were also prevented by this drug. Malotilate drastically reduced the increases in the amount of type I procollagen alpha 2-chain mRNA and activities of the enzymes prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, which are early events in liver fibrosis preceding the deposition of collagen. Even when started 14 days after dimethylnitrosamine induction, malotilate treatment was able to reduce liver damage. We suggest that the effect of malotilate is a result of the inhibition of inflammation.
Ala-Kokko
L
L
Department of Medical Biochemistry, University of Oulu, Finland.
Stenbäck
F
F
Ryhänen
L
L
D000818:Animals; D003094:Collagen / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects; D008314:Malonates / Q000494:pharmacology*; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D008314:Malonates; D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen; D004128:Dimethylnitrosamine; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate