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Acta Haematologica 2019
Topics: Anemia, Sickle Cell; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Incidence; Venous Thromboembolism; Vitamin K
PubMed: 31315111
DOI: 10.1159/000501442 -
The Journal of Nutrition Apr 2022Vitamin K is a term that comprises a family of structurally related quinones, phylloquinone (PK) and the menaquinones (MKn), that share a common naphthoquinone ring but...
BACKGROUND
Vitamin K is a term that comprises a family of structurally related quinones, phylloquinone (PK) and the menaquinones (MKn), that share a common naphthoquinone ring but vary in sidechain length (n) and saturation. Dietary PK is a biosynthetic precursor to tissue menaquinone-4 (MK4), but little is known about the absorption and metabolism of dietary MKn.
OBJECTIVE
To characterize the absorption and metabolism of dietary MKn relative to PK.
METHODS
In the 4-week diet study, 10-week-old male and female C57BL/6 mice were pair-fed a vitamin K deficient diet (control) or a diet supplemented with 5.0 μmol/kg total PK, MK4, and/or MK9 (separately and in combination). In the 1-week stable isotope study, 12-week-old mice were pair-fed diets containing 2.2 μmol/kg PK (unlabeled control), 2H7PK, 13C11MK4, 2H7MK7, or 2H7MK9. Vitamin K tissue content was quantified by HPLC and/or LC-MS, and concentrations were compared by sex and diet group using 2-factor ANOVA.
RESULTS
Regardless of the form(s) of vitamin K provided in the diet, tissue MK4 concentrations did not differ across equimolar supplemented groups in the kidney, adipose, reproductive organ, bone, or pancreas in either males or females in the diet study (all P values > 0.05). Isotopic labeling confirmed the naphthoquinone ring of MK4 in tissues originated from the administered dietary PK or MKn. Despite equimolar supplementation, accumulation of the administered dietary form differed across diet groups in small intestinal segments (all P values < 0.002) and the liver (P < 0.001). Female mice had greater total vitamin K than males in every tissue examined (P < 0.05).
CONCLUSIONS
Dietary PK, MK4, MK7, and MK9 all served as precursors to tissue MK4 in mice. This study expands our understanding of vitamin K metabolism and supports a common conversion mechanism of all dietary vitamin K forms to MK4. Further investigation of the metabolism and physiological roles of MK4 that may be independent of classical vitamin K function is warranted.
Topics: Animals; Diet; Female; Male; Mice; Mice, Inbred C57BL; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 34550377
DOI: 10.1093/jn/nxab332 -
Blood May 1990
Comparative Study Review
Topics: Amino Acid Sequence; Blood Proteins; Carbon-Carbon Ligases; Humans; Ligases; Molecular Sequence Data; Sequence Homology, Nucleic Acid; Substrate Specificity; Vitamin K
PubMed: 2184900
DOI: No ID Found -
Blood Mar 1999
Review
Topics: 1-Carboxyglutamic Acid; Amino Acid Sequence; Animals; Blood Coagulation Factors; Carbon-Carbon Ligases; Humans; Molecular Sequence Data; Vitamin K
PubMed: 10068650
DOI: No ID Found -
Nutrients Jul 2021Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK may reduce... (Review)
Review
Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK may reduce the risk of death in patients with chronic liver failure. VK deficiency is associated with intrahepatic cholestasis, and is already being used as a drug for cholestasis-induced liver fibrosis in China. In Japan, to treat osteoporosis in patients with primary biliary cholangitis, VK formulations are prescribed, along with vitamin D. Animal studies have revealed that after bile duct ligation-induced cholestasis, PXR knockout mice manifested more hepatic damage than wild-type mice. Ligand-mediated activation of PXR improves biochemical parameters. Rifampicin is a well-known human PXR ligand that has been used to treat intractable pruritus in severe cholestasis. In addition to its anti-cholestatic properties, PXR has anti-fibrotic and anti-inflammatory effects. However, because of the scarcity of animal studies, the mechanism of the effect of VK on cholestasis-related liver disease has not yet been revealed. Moreover, the application of VK in cholestasis-related diseases is controversial. Considering this background, the present review focuses on the effect of VK in cholestasis-related diseases, emphasizing its function as a modulator of PXR.
Topics: Animals; Bile Acids and Salts; Cholestasis, Intrahepatic; Dietary Supplements; Humans; Mice; Pregnane X Receptor; Vitamin K; Vitamin K Deficiency
PubMed: 34444675
DOI: 10.3390/nu13082515 -
Nephrology, Dialysis, Transplantation :... Feb 2023Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.
BACKGROUND
Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease.
METHODS
A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest.
RESULTS
A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups.
CONCLUSION
We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.
Topics: Humans; Vitamin K; Vitamin K 1; Osteocalcin; Pilot Projects; Coronary Artery Disease; Vascular Calcification; Calcium-Binding Proteins; Extracellular Matrix Proteins; Renal Dialysis; Vitamin K 2
PubMed: 35641194
DOI: 10.1093/ndt/gfac191 -
The Korean Journal of Parasitology Aug 2016There is renewed interest in natural products as a starting point for discovery of drugs for schistosomiasis. Recent studies have shown that phytol reveals interesting...
There is renewed interest in natural products as a starting point for discovery of drugs for schistosomiasis. Recent studies have shown that phytol reveals interesting in vivo and in vitro antischistosomal properties against Schistosoma mansoni adult worms. Here, we report the in vitro antischistosomal activity of phytol against Schistosoma haematobium juvenile and adult worms and alterations on the tegumental surface of the worms by means of scanning electron microscopy. The assay, which was carried out with 6 concentrations (25, 50, 75, 100, 125, and 150 μg/ml) of phytol, has shown a promising activity in a dose and time-dependent manner. There was a significant decline in the motility of the worms and a mortality rate of 100% was found at 48 hr after they had been exposed to phytol in the concentration of 150 μg/ml. Male worms were more susceptible. On the ultrastructural level, phytol also induced tegumental peeling, disintegration of tubercles and spines in addition to morphological disfiguring of the oral and ventral suckers. This report provides the first evidence that phytol is able to kill S. haematobium of different ages, and emphasizes that it is a promising natural product that could be used for development of a new schistosomicidal agent.
Topics: Animals; Anthelmintics; Dose-Response Relationship, Drug; Female; Integumentary System; Locomotion; Male; Mesocricetus; Microscopy, Electron, Scanning; Phytol; Schistosoma haematobium; Snails; Survival Analysis; Time Factors
PubMed: 27658600
DOI: 10.3347/kjp.2016.54.4.477 -
Journal of Experimental Botany Dec 2017In a changing environment, plants need to cope with the impact of rising temperatures together with high light intensity. Here, we used lipidomics in the tomato model...
In a changing environment, plants need to cope with the impact of rising temperatures together with high light intensity. Here, we used lipidomics in the tomato model system to identify lipophilic molecules that enhance tolerance to combined high-temperature and high-light stress. Among several hundred metabolites, the two most strongly up-regulated compounds were α-tocopherol and plastoquinone/plastoquinol. Both are well-known lipid antioxidants and contribute to the protection of photosystem II (PSII) against photodamage under environmental stress. To address the protective function of tocopherol, an RNAi line (vte5) with decreased expression of VTE5 and reduced levels of α-tocopherol was selected. VTE5 encodes phytol kinase, which acts in the biosynthetic pathway of tocopherols. vte5 suffered strong photoinhibition and photobleaching when exposed to combined high-light and high-temperature stress, but neither stress alone produced a visible phenotype. As vte5 had plastoquinone levels similar to those of the wild type under combined stress, the strong phenotype could be attributed to the lack of α-tocopherol. These findings suggest that VTE5 protects against combined high-light and high-temperature stress and does so by supporting α-tocopherol production.
Topics: Light; Solanum lycopersicum; Phosphotransferases; Phytol; Plant Proteins; Stress, Physiological; Temperature; Tocopherols
PubMed: 29186558
DOI: 10.1093/jxb/erx356 -
Nutrients Oct 2023Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often...
Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.
Topics: Male; Humans; Female; Adult; Vitamin K 2; Enteral Nutrition; Intellectual Disability; Prothrombin; Biomarkers; Vitamin K; Osteocalcin; Vitamin K Deficiency; Dietary Supplements; Vitamin K 1
PubMed: 37960177
DOI: 10.3390/nu15214525 -
Applied and Environmental Microbiology Nov 2020Enterohemorrhagic (EHEC) causes serious foodborne disease worldwide. It produces the very potent Shiga toxin 2 (Stx2). The Stx2-encoding genes are located on a...
Enterohemorrhagic (EHEC) causes serious foodborne disease worldwide. It produces the very potent Shiga toxin 2 (Stx2). The Stx2-encoding genes are located on a prophage, and production of the toxin is linked to the synthesis of Stx phages. There is, currently, no good treatment for EHEC infections, as antibiotics may trigger lytic cycle activation of the phages and increased Stx production. This study addresses how four analogs of vitamin K, phylloquinone (K1), menaquinone (K2), menadione (K3), and menadione sodium bisulfite (MSB), influence growth, Stx2-converting phage synthesis, and Stx2 production by the EHEC O157:H7 strain EDL933. Menadione and MSB conferred a concentration-dependent negative effect on bacterial growth, while phylloquinone or menaquinone had little and no effect on bacterial growth, respectively. All four vitamin K analogs affected Stx2 phage production negatively in uninduced cultures and in cultures induced with either hydrogen peroxide (HO), ciprofloxacin, or mitomycin C. Menadione and MSB reduced Stx2 production in cultures induced with either HO or ciprofloxacin. MSB also had a negative effect on Stx2 production in two other EHEC isolates tested. Phylloquinone and menaquinone had, on the other hand, variable and concentration-dependent effects on Stx2 production. MSB, which conferred the strongest inhibitory effect on both Stx2 phage and Stx2 production, improved the growth of EHEC in the presence of HO and ciprofloxacin, which could be explained by the reduced uptake of ciprofloxacin into the bacterial cell. Together, the data suggest that vitamin K analogs have a growth- and potential virulence-reducing effect on EHEC, which could be of therapeutic interest. Enterohemorrhagic (EHEC) can cause serious illness and deaths in humans by producing toxins that can severely damage our intestines and kidneys. There is currently no optimal treatment for EHEC infections, as antibiotics can worsen disease development. Consequently, the need for new treatment options is urgent. Environmental factors in our intestines can affect the virulence of EHEC and help our bodies fight EHEC infections. The ruminant intestine, the main reservoir for EHEC, contains high levels of vitamin K, but the levels are variable in humans. This study shows that vitamin K analogs can inhibit the growth of EHEC and/or production of its main virulence factor, the Shiga toxin. They may also inhibit the spreading of the Shiga toxin encoding bacteriophage. Our findings indicate that vitamin K analogs have the potential to suppress the development of serious disease caused by EHEC.
Topics: Anti-Bacterial Agents; Coliphages; Escherichia coli O157; Shiga Toxin 2; Virulence; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3; Vitamins
PubMed: 32769190
DOI: 10.1128/AEM.00583-20