Dalteparin did not prevent acute CCl(4)-induced hepatic necrosis and elevation in serum aminotransferases levels; however, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were dramatically increased 24h after simultaneous administration of CCl(4) and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12h after injection of CCl(4) were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl(4) treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl(4)-induction of smooth muscle alpha-actin expression, alpha1(I)procollagen and transforming growth factor (TGF)-beta1 mRNA levels in the liver. Further, dalteparin blunted platelet-derived growth factor (PDGF)-induced increases in 5-bromo-2’deoxyuridine (BrdU) uptake in 3-day cultured hepatic stellate cells (HSCs) in a dose-dependent manner.
PMID: 17166617 (J Hepatol)