Effects of KF-14363 on Liver Fibrosis in Rats with Chronic Liver Injury Induced by Carbon Tetrachloride

  • YOSHITAKE Ikufumi
    Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co., Ltd.
  • OHISHI Eiko
    Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co., Ltd.
  • SANO Junichi
    Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co., Ltd.
  • MORI Tatsuya
    Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co., Ltd.
  • KUBO Kazuhiro
    Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co., Ltd.

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The present study examined the effects of (1-[(2-thiazolin-2-yl) amino]-acetyl-4-(1,3-dithiol-2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride (CCl_4). Liver injury in male rats was induced by repeated administration of CCl_4 at 0.5 ml/kg twice a week. The progression of liver fibrosis was checked in the 4th, 6th, 8th and 10th weeks using the relative amount of hepatic 4-hydroxy proline (4-hyp) to total proteine as an index of hepatic collagen. The relative amount of hepatic 4-hyp in these rats exceeded significantly that in rats not administered CCl_4 by the 4th week. This progressed in proportion to the duration of CCl_4 administration. In groups concurrently administered KF-14363 at 30 and 100 mg/kg/d from the 5th or 8th week of the CCl_4 administration, the relative amount of hepatic 4-hyp was found to be lower in the 10th week than at the start of the KF-14363 administration. The inhibition of liver fibrosis was also observed histopathologically. The concurrently co-administration with CCl_4 or KF-14363 at 30 and 100 mg/kg for 2 or 5 weeks inhibited the increases in serum transaminases and alkaline phosphatase induced by CCl_4. The results show that KF-14363 inhibits liver fibrosis in a dose dependent fashion in rats with progressive liver injury.

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