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

• Published in: Journal of Nutritional Science and Vitaminology Vol. 67; no. 6; pp. 397 - 403
• Main Authors: HOSHINO, Yoshiki, SUGIHARA, Takaaki, IKEDA, Suguru, TARUMOTO, Ryohei, MATSUKI, Yukako, KANDA, Tsutomu, IYAMA, Takuji, TAKATA, Tomoaki, MATONO, Tomomitsu, NAGAHARA, Takakazu, OKANO, Jun-ichi, UEKI, Masaru, KODA, Masahiko, OSAKI, Mitsuhiko, OKADA, Futoshi, ISOMOTO, Hajime
• Format: Journal Article
• Language: English
• Published: Japan Center for Academic Publications Japan 01.01.2021
• Subjects: Animals; Bile Ducts - surgery; Cholestasis; cirrhosis; coagulopathy; Jaundice, Obstructive - drug therapy; Jaundice, Obstructive - etiology; Liver; obstructive jaundice; Prothrombin Time; Rats; vitamin K; Vitamin K 2; coagulopathy; cholestasis; obstructive jaundice; vitamin K; cirrhosis
• ISSN: 0301-4800; 1881-7742
• DOI: 10.3177/jnsv.67.397

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.