Inhibitory effect of acyclic retinoid (polyprenoic acid) on hepatic fibrosis in CCl4-treated rats
A study was conducted to examine the inhibitory effect of acyclic retinoid (polyprenoic acid) on the development of hepatic fibrosis induced by CC14 in rats. Oral administration of the compound brought about a significant reduction in both serum and tissue levels of immunoreactive prolyl hydroxylase, a key enzyme of collagen formation. The result indicated that the rate of collagen synthesis in the liver was decreased which was consistent with histological findings. Acyclic retinoid also decreased both AST and ALT activities in serum, demonstrating the reduction in hepatic parenchymal damage. This cytoprotective effect on parenchymal cells may be related, at least in part, to inhibition of hepatic fibrosis. No significant side effects were observed, despite a long-term administration of the acyclic retinoid. The present findings suggest the potential scope of therapy of hepatic fibrosis by retinoid.
Key wordscarbon tetrachloride hepatic fibrosis hydroxyproline prolyl hydroxylase retinoid
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- 2.Popper H: Hepatic fibrosis and collagen metabolism in the liver. In: Popper H, Beker K, eds. Collagen metabolism in the liver. Stratton Intercontinental Medical Book Corp, New York. 1975; 1–14Google Scholar
- 3.Moon RC, Itri LM: Rctinoids and Cancer. In: Sporn MB, Roberts AB, Goodman DS, eds. The Retinoids, Vol 2. Academic Press, New York. 1984;327-371Google Scholar
- 4.Muto Y, Moriwaki H: Antitumor activity of vitamin A and its derivatives. J Natl Cancer Inst 1984;47:2025–2044Google Scholar
- 6.Kamm JJ, Ashenfelter KO, Ehmann CW: Preclinical and clinical toxicology of selected retinoids. In: Sporn MB, Roberts AB, Goodman DS, eds. The Retinoids, Vol.2. Academic Press, New York. 1984;287-326Google Scholar
- 10.Prockop DJ, Berg RA, Kivirikko Kl, et al: Intracellular steps in the biosynthesis of collagen. In: Ramachandran GN, Reddi AH, eds. Biochemistry of collagen. Plenum Publishing Corp, New York. 1976;163–273Google Scholar
- 11.Muragaki Y: Experimental study on alteration of collagen metabolism in liver fibrosis. J Wakayama Med Soc 1985 ;26:195–208Google Scholar
- 12.Miyabishi C, Inoue K, Takahara T, et al: Serum prolyl hydroxylase value in liver diseases. Jpn J Gastroenterol 1986;83:2181–2189 (in Jpn)Google Scholar
- 13.Okai T, Satomura Y, Ohta H, et al: Serum prolyl hydroxylase levels in patients with various liver diseases. Acta Hepat Jap 1987;28:262–263 (in Jpn)Google Scholar
- 14.Yasuhara M, Matsushita Y, Takada A: Clinical significance of serum prolyl hydroxylase β-subunit levels determined using monoclonal antibody. Jpn J Gastroenterol 1987;84:1225–1232(in Jpn)Google Scholar
- 15.Suzuki H, Suzuki M, Okabe K, et al: Clinical significance of the determination of serum prolyl hydroxylase (IRPH) in hepatic fibrosis. Jpn J Gastroenterol 1987;84:1265–1271 (in Jpn)Google Scholar
- 18.Prockop DJ, Udenfriend S: A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem 1960;1:228–239Google Scholar
- 20.Hata R, Ninomiya Y, Nagai Y, et al: Active synthesis of collagen by albumin-producing liver parenchymal cell clones in culture. Proc Japan Acad Ser 1978;B54:391–396Google Scholar