Atorvastatin Decreases Renal Menaquinone-4 Formation in C57BL/6 Male Mice

Menaquinone-4 (MK4), a vitamin K metabolite, is converted from phylloquinone through a process that requires intermediates of endogenous cholesterol production. Recent evidence suggests that MK4 is involved in kidney function. The purpose of this study was to determine the effect of atorvastatin tre...

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Bibliographic Details
Published in:The Journal of nutrition 2019-03, Vol.149 (3), p.416-421
Main Authors: Harshman, Stephanie G, Shea, M Kyla, Fu, Xueyan, Grusak, Michael A, Smith, Donald, Lamon-Fava, Stefania, Kuliopulos, Athan, Greenberg, Andrew, Booth, Sarah L
Format: Article
Language:English
Subjects:
Age
Animal models
Animal tissues
Animals
Atmospheric models
Atorvastatin
Atorvastatin - pharmacology
Brain
Cholesterol
Cholesterol - blood
cholesterol intermediates
Coenzyme A
Deuterium
Diet
Gene expression
Gene Expression Regulation - drug effects
geranylgeranyl pyrophosphate
Hydroxymethylglutaryl-CoA reductase
Intermediates
Intestine
Ionization
Kidneys
Lipid metabolism
Liver
Male
Males
menaquinones
Metabolism
Mice
Mice, Inbred C57BL
Organic chemistry
Organs
Original
Phylloquinone
Polymerase chain reaction
Prescription drugs
Regulatory mechanisms (biology)
RNA-directed DNA polymerase
Rodents
statins
Tissues
Triglycerides - blood
Vitamin K
Vitamin K 2 - analogs & derivatives
Vitamin K 2 - metabolism
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Summary:Menaquinone-4 (MK4), a vitamin K metabolite, is converted from phylloquinone through a process that requires intermediates of endogenous cholesterol production. Recent evidence suggests that MK4 is involved in kidney function. The purpose of this study was to determine the effect of atorvastatin treatment on MK4 formation in young and old male mice. C57BL/6 male mice (4-mo-old and 20-mo-old) were randomly assigned to either a diet containing 300 mg atorvastatin/kg with 3 mg phylloquinone/kg or a control diet containing 3 mg phylloquinone/kg for 8 wk. During week 8, all mice received deuterium-labeled phylloquinone in the diet. Labeled and unlabeled phylloquinone and MK4 in liver, kidney, brain, and intestine were measured by atmospheric pressure chemical ionization LC/MS. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene expression was quantified by reverse transcriptase-PCR. Tissue MK4 and phylloquinone concentrations were compared between atorvastatin treatment groups with use of general linear models. There was no age-treatment interaction on MK4 tissue concentrations. In atorvastatin-treated mice, total MK4 and percentage of deuterium-labeled MK4 in kidney were both approximately 45% lower compared to values in mice not given atorvastatin (all P 
ISSN:0022-3166
1541-6100
DOI:10.1093/jn/nxy290