Establishing a rat model for the study of vitamin K deficiency

Yanni Mi; Xue Xiao; Dongzheng Liu; Nana Ping; Yanbing Zhu; Bo Li; Lihui Long; Yongxiao Cao

doi:10.1111/iep.12178

Establishing a rat model for the study of vitamin K deficiency

International Journal of Experimental Pathology ◽

10.1111/iep.12178 ◽

2016 ◽

Vol 97 (2) ◽

pp. 187-193 ◽

Cited By ~ 3

Author(s):

Yanni Mi ◽

Xue Xiao ◽

Dongzheng Liu ◽

Nana Ping ◽

Yanbing Zhu ◽

...

Keyword(s):

Vitamin K ◽

Rat Model ◽

Vitamin K Deficiency ◽

K Deficiency

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Vitamin K Metabolism in a Rat Model of Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000451068 ◽

2016 ◽

Vol 45 (1) ◽

pp. 4-13 ◽

Cited By ~ 12

Author(s):

Kristin M. McCabe ◽

Sarah L. Booth ◽

Xueyan Fu ◽

Emilie Ward ◽

Michael A. Adams ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K ◽

Rat Model ◽

Relative Increase ◽

Kidney Cortex ◽

Vitamin K Deficiency ◽

Tissue Concentrations ◽

K Deficiency ◽

Very High

Background: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues. Methods: In the present study, we assessed tissue concentrations of K1 and MK-4 and the expression of vitamin K-related genes in a rat model of adenine-induced CKD. Results: It was found that rats with both mild and severe CKD had significantly lower amounts of K1 measured in liver, spleen and heart and higher levels of MK-4 measured in kidney cortex and medulla. All animals treated with high dietary K1 had an increase in tissue levels of both K1 and MK-4; however, the relative increase in K1 differed suggesting that the conversion of K1 to MK-4 may be a regulated/limiting process in some tissues. There was a decrease in the thoracic aorta expression of vitamin K recycling (Vkor) and utilization (Ggcx) enzymes, and a decrease in the kidney level of vitamin K1 to MK-4 bioconversion enzyme Ubiad1 in CKD. Conclusion: Taken together, these findings suggest that CKD impacts vitamin K metabolism, and this occurs early in the disease course. Our findings that vitamin K metabolism is altered in the presence of CKD provides further support that sub-clinical vitamin K deficiency may represent a modifiable risk factor for vascular and bone health in this population.

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Placental Transfer of Vitamin K1 and Its Implications in Fetal Hemostasis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647631 ◽

1988 ◽

Vol 60 (01) ◽

pp. 039-043 ◽

Cited By ~ 52

Author(s):

L Mandelbrot ◽

M Guillaumont ◽

M Leclercq ◽

J J Lefrère ◽

D Gozin ◽

...

Keyword(s):

Vitamin K ◽

High Performance ◽

Ultrasound Guidance ◽

Placental Transfer ◽

Vitamin K1 ◽

Vitamin K Deficiency ◽

Prothrombin Activity ◽

Oral Supplementation ◽

K Deficiency ◽

The Mean

SummaryVitamin K status was evaluated using coagulation studies and/ or vitamin IQ assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate.After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60 fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.

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Kinetic Aspects of the Interaction of Blood-Clotting Enzymes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651250 ◽

1968 ◽

Vol 20 (01/02) ◽

pp. 078-087 ◽

Cited By ~ 34

Author(s):

H. C Hemker ◽

A. D Muller

Keyword(s):

Vitamin K ◽

Blood Clotting ◽

Experimental Results ◽

Factor X ◽

Clotting Factors ◽

Vitamin K Deficiency ◽

K Deficiency

SummaryPIVKA, the circulating anticoagulant protein found in vitamin K deficiency can, on kinetical grounds, be recognized as an analogue of factor X. The existence of analogues of other vitamin K-dependent clotting factors cannot be ruled out, but need not be assumed to explain the experimental results.

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