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Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis

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Abstract

Purpose

The aim of this study is to investigate the role of hepatic stellate cells (HSCs) and the effect of vitamin A administration on liver damage induced by bile duct ligation (BDL) and administration of CCl4.

Methods

Two types of animal model were used; one was BDL as a model of biliary atresia, the other was CCl4-induced hepatic fibrosis. Pathological changes of the liver with or without administration of vitamin A were compared by light and electron microscopy with focusing on HSCs in each experimental group. Immunohistochemical examination was performed with anti-keratinocyte growth factor (KGF), anti-alpha-smooth muscle actin (α-SMA), and anti-glial fibrillary acidic protein (GFAP) antibodies, as markers of fibrosis.

Results

On light microscopic findings, periportal inflammation with bile ductular proliferation was obvious in BDL group and pericentral necrosis with fatty degeneration was observed in CCl4 group, both of which were ameliorated by subcutaneous injection of vitamin A. Electron microscopy showed lipid droplets were almost depleted in the HSCs treated with BDL or CCl4, which improved with vitamin A administration. Immunohistochemistry demonstrated that enhanced expression of all three fibrotic markers in the BDL group was diminished by vitamin A administration.

Conclusions

Although most of our data are qualitative observation, vitamin A may ameliorate hepatic fibrosis in the BDL model by restoring vitamin A in the HSCs.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Ken-ichi Murakami & Hiroshi Matsufuji

  2. Department of Pediatric Surgery, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Tatsuru Kaji, Ryuichi Shimono & Yoshihiro Hayashida

  3. Department of Structural Cell Biology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Shinichiro Tsuyama, Rie Maezono & Ken-ichiro Kosai

  4. Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Hideo Takamatsu

Authors
  1. Ken-ichi Murakami
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  2. Tatsuru Kaji
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  4. Yoshihiro Hayashida
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  6. Shinichiro Tsuyama
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  7. Rie Maezono
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  8. Ken-ichiro Kosai
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  9. Hideo Takamatsu
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Correspondence to Ken-ichi Murakami.

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Murakami, Ki., Kaji, T., Shimono, R. et al. Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis. Pediatr Surg Int 27, 863–870 (2011). https://doi.org/10.1007/s00383-011-2853-0

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  • DOI: https://doi.org/10.1007/s00383-011-2853-0

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