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1996 Fiscal Year Final Research Report Summary

IMMUNOPHARMACOLOGICAL STUDIES ON FULMINANT HEPATITIS MODEL USING THE SPHEROID CULTURE OF RAT LIVER CELLS

Research Project

Project/Area Number 07672343
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

UENO Koichi  CHIBA UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES, 薬学部, 助教授 (60125903)

Project Period (FY) 1995 – 1996
KeywordsSPHEROID / FULMINANT HEPATITIS / IMMUNITY / CYTOKINES / IL-8 / RAT / LEC / HEPATITIS MODEL
Research Abstract

An experimental acute liver injury model can be produced by the injection of bacterial lipopolysaccharide (LPS) into Propionibacterium acnes (P.acnes) pretreated rats. The massive liver cell necrosis is estimated by elevation of serum transaminase activities. In this study, we produced this necrosis in an in vitro model by using primary co-cultured rat liver cells. A novel method for the preparation of spheroids consisting of P.acnes pretreated parechymal and nonparechymal liver cells has been successfully developed quickly by the rotary culture system within 24 h although it takes 7 days to form the spheroid using a collagen-conjugated thermo-responsive polymer such as a cell substratum. Clear elevations of transaminase activities, TNF-a and CINC-1/gro/KC (IL-8) leaked from these spheroids into the medium caused by the exposure of 10 mug/ml LPS for 48 h were observed. These results suggest that this rotary co-culture system of rat liver cells is useful model as an alternative to animal tests for fulminant hepatitis. Therefore, several hepato-protective agents, tiopronin, bucillamine, catechin, gomisin A,and zinc porphyrins, were screened. These agents showed obvious hepato-protective activities in this hepatitis model as well as in vivo.
On the other hand, the distribution of copper in spheroids was examined using multicellular spheroids of LEC rat liver cells. When LEC rat spheroids were exposed to CuC12 at concentrations of more than 50 muM for 24h, copper contents in LEC rat spheroids were maintained for 24h after the withdrawal of CuC12 and higher than those of the SD rat spheroid.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Koichi Ueno: "Abnormal hepatic copper accumulation of spheroid oomposed of liver cells from LEC rats in vitro" Res.Commun.Molec.Pathol.Pharmacol.90・2. 191-210 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koichi Ueno: "Rapid formation of multicellular spheroids composed of Propionibacterium acnes pretreated adult rat liver cells by rotary culture and their immunologicalpropert" Res.Commun.Molec.Pathol.Pharmacol.90・3. 373-387 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koichi Ueno et al.: "Abnormal hepatic copper accumulation of spheroid composed of liver cells from LEC rats in vitro." Res.Commun.Molec.Pathol.Pharmacol.90 (2). 191-210 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koichi Ueno et al.: "Rapid formation of multicellular spheroids composed of Propionoibacterium acnes pretreated adult rat liver cells by rotary culture and their immunological properties." Res.Commun.Molec.Pathol.Pharmacol.90 (2). 191-210 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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