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Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat.
J Hepatol 2007; 46(2):286-94JH

Abstract

BACKGROUND/AIMS

In this study, we investigated the effect of dalteparin sodium, a low molecular weight (LMW)-heparin, on hepatic fibrogenesis caused by chronic carbon tetrachloride (CCl4) administration in the rat.

METHODS

Female Wistar rats were given a single, or repeated intraperitoneal injections of CCl4 (1ml/kg, twice per week) and dalteparin (50IU/kg, daily) for 7 weeks.

RESULTS

Dalteparin did not prevent acute CCl4-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 CCl4 and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12h after injection of CCl4 were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl4 treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl4-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.

CONCLUSIONS

Dalteparin enhances hepatic regeneration and minimizes hepatic fibrogenesis caused by chronic CCl4 treatment. The mechanism underlying these effects most likely involves both up-regulation of HGF and inhibition of HSC proliferation.

Authors+Show Affiliations

Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17166617

Citation

Abe, Wataru, et al. "Low Molecular Weight Heparin Prevents Hepatic Fibrogenesis Caused By Carbon Tetrachloride in the Rat." Journal of Hepatology, vol. 46, no. 2, 2007, pp. 286-94.
Abe W, Ikejima K, Lang T, et al. Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat. J Hepatol. 2007;46(2):286-94.
Abe, W., Ikejima, K., Lang, T., Okumura, K., Enomoto, N., Kitamura, T., ... Sato, N. (2007). Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat. Journal of Hepatology, 46(2), pp. 286-94.
Abe W, et al. Low Molecular Weight Heparin Prevents Hepatic Fibrogenesis Caused By Carbon Tetrachloride in the Rat. J Hepatol. 2007;46(2):286-94. PubMed PMID: 17166617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat. AU - Abe,Wataru, AU - Ikejima,Kenichi, AU - Lang,Tie, AU - Okumura,Kyoko, AU - Enomoto,Nobuyuki, AU - Kitamura,Tsuneo, AU - Takei,Yoshiyuki, AU - Sato,Nobuhiro, Y1 - 2006/10/25/ PY - 2006/04/02/received PY - 2006/08/18/revised PY - 2006/08/27/accepted PY - 2006/12/15/pubmed PY - 2007/3/17/medline PY - 2006/12/15/entrez SP - 286 EP - 94 JF - Journal of hepatology JO - J. Hepatol. VL - 46 IS - 2 N2 - BACKGROUND/AIMS: In this study, we investigated the effect of dalteparin sodium, a low molecular weight (LMW)-heparin, on hepatic fibrogenesis caused by chronic carbon tetrachloride (CCl4) administration in the rat. METHODS: Female Wistar rats were given a single, or repeated intraperitoneal injections of CCl4 (1ml/kg, twice per week) and dalteparin (50IU/kg, daily) for 7 weeks. RESULTS: Dalteparin did not prevent acute CCl4-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 CCl4 and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12h after injection of CCl4 were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl4 treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl4-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. CONCLUSIONS: Dalteparin enhances hepatic regeneration and minimizes hepatic fibrogenesis caused by chronic CCl4 treatment. The mechanism underlying these effects most likely involves both up-regulation of HGF and inhibition of HSC proliferation. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/17166617/Low_molecular_weight_heparin_prevents_hepatic_fibrogenesis_caused_by_carbon_tetrachloride_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(06)00513-7 DB - PRIME DP - Unbound Medicine ER -