Newly Invented Micellized Vitamin K2 Recovered Prolonged Prothrombin Time under Obstructive Jaundice in Rats with Bile Duct Ligation

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  • HOSHINO Yoshiki
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • SUGIHARA Takaaki
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • IKEDA Suguru
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • TARUMOTO Ryohei
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • MATSUKI Yukako
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • KANDA Tsutomu
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • IYAMA Takuji
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • TAKATA Tomoaki
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • MATONO Tomomitsu
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • NAGAHARA Takakazu
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • OKANO Jun-ichi
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University
  • UEKI Masaru
    Division of Medical Education, School of Medicine, Tottori University
  • KODA Masahiko
    Department of Internal Medicine, Hino Hospital
  • OSAKI Mitsuhiko
    Division of Experimental Pathology, School of Medicine, Tottori University
  • OKADA Futoshi
    Division of Experimental Pathology, School of Medicine, Tottori University
  • ISOMOTO Hajime
    Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University

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Abstract

<p>In cholestatic liver diseases, coagulopathy is induced by malabsorption of vitamin K. Supplementation of vitamin K has previously been shown to prevent coagulopathy. In this study, we tested the efficacy of a newly invented micellized vitamin K2 (m-vitK2) in treating coagulopathy, using a rat bile duct ligation (BDL) model. Experiment 1: m-vitK2 (0.3 mg/kg) or m-vitK2 (0.3 mg/kg) mixed with taurocholic acid (TA) (10 mg/body) was orally administrated every day for 7 d from the fourth day after BDL (n=6 for each). Experiment 2: To evaluate absorption, m-vitK2 (0.3 mg/kg) with or without TA (10 mg/body) was orally administered on the fourth day after BDL and compared with the untreated control BDL (n=2 for each). These data were compared with sham-operated (n=6) and untreated control BDL rats (n=6). The m-vitK2 recovered prothrombin time (PT) in Experiment 1 (control 42.7±5.7 s vs. m-vitK2 24.0±9.3 s, p<0.05). Experiment 2 demonstrated that the mixture of m-vitK2 and TA enhanced absorption compared to m-vitK2 alone. Moreover, in Experiment 1, m-vitK2 mixed with TA completely recovered PT (control 42.7±5.7 s vs. m-vitK2+TA 14.9±1.2 s, p<0.01). Micelle sizes decreased with the m-vitK2 and TA treatment (m-vitK2 86.3±5.6 nm vs. m-vitK2+TA 71.9±4.7 nm, p<0.05). Orally administered, newly invented m-vitK2 recovered coagulopathy even under obstructive jaundice. TA decreased the mean micelle size and improved m-vitK2 absorption.</p>

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