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Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7

Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arterie...

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Autores principales: Pucaj, Kresimir, Rasmussen, Henrik, Moller, Mona, Preston, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Informa Healthcare 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172146/
https://www.ncbi.nlm.nih.gov/pubmed/21781006
http://dx.doi.org/10.3109/15376516.2011.568983
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author Pucaj, Kresimir
Rasmussen, Henrik
Moller, Mona
Preston, Tom
author_facet Pucaj, Kresimir
Rasmussen, Henrik
Moller, Mona
Preston, Tom
author_sort Pucaj, Kresimir
collection PubMed
description Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arteries. The objective of this study was to examine the potential toxicity of synthetic MK-7 in BomTac:NMRI mice and in Sprague-Dawley rats. In an acute oral toxicity test, mice were administered a single oral dose of 2000 mg/kg body weight (limit dose) and no toxicity was observed during the 14-day observation period. In the subchronic oral toxicity test in rats, animals were administered MK-7 for 90 days by gavage at the following doses: 0 (vehicle control, corn oil), 2.5, 5, and 10 mg/kg body weight/day. All generated data, including clinical observations, ophthalmology, clinical pathology, gross necropsy, and histopathology, revealed no compound-related toxicity in rats. Any statistically significant findings in clinical pathology parameters and/or organ weights noted were considered to be within normal biological variability. Therefore, under the conditions of this experiment, the median lethal dose (LD(50)) of MK-7 after a single oral administration in mice was determined to be greater than the limit dose level of 2000 mg/kg body weight. The no observed adverse effect level (NOAEL) of MK-7, when administered orally to rats for 90 days, was considered to be equal to 10 mg/kg body weight/day, the highest dose tested, based on lack of toxicity during the 90-day study period.
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spelling pubmed-31721462011-09-15 Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7 Pucaj, Kresimir Rasmussen, Henrik Moller, Mona Preston, Tom Toxicol Mech Methods Research Article Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arteries. The objective of this study was to examine the potential toxicity of synthetic MK-7 in BomTac:NMRI mice and in Sprague-Dawley rats. In an acute oral toxicity test, mice were administered a single oral dose of 2000 mg/kg body weight (limit dose) and no toxicity was observed during the 14-day observation period. In the subchronic oral toxicity test in rats, animals were administered MK-7 for 90 days by gavage at the following doses: 0 (vehicle control, corn oil), 2.5, 5, and 10 mg/kg body weight/day. All generated data, including clinical observations, ophthalmology, clinical pathology, gross necropsy, and histopathology, revealed no compound-related toxicity in rats. Any statistically significant findings in clinical pathology parameters and/or organ weights noted were considered to be within normal biological variability. Therefore, under the conditions of this experiment, the median lethal dose (LD(50)) of MK-7 after a single oral administration in mice was determined to be greater than the limit dose level of 2000 mg/kg body weight. The no observed adverse effect level (NOAEL) of MK-7, when administered orally to rats for 90 days, was considered to be equal to 10 mg/kg body weight/day, the highest dose tested, based on lack of toxicity during the 90-day study period. Informa Healthcare 2011-09 2011-07-25 /pmc/articles/PMC3172146/ /pubmed/21781006 http://dx.doi.org/10.3109/15376516.2011.568983 Text en © 2011 Informa Healthcare USA, Inc. http://creativecommons.org/licenses/by/2.0/ This is an open access article distributed under the Supplemental Terms and Conditions for iOpenAccess articles published in Informa Healthcare journals (http://www.informaworld.com/mpp/uploads/iopenaccess_tcs.pdf) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pucaj, Kresimir
Rasmussen, Henrik
Moller, Mona
Preston, Tom
Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
title Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
title_full Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
title_fullStr Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
title_full_unstemmed Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
title_short Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
title_sort safety and toxicological evaluation of a synthetic vitamin k2, menaquinone-7
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172146/
https://www.ncbi.nlm.nih.gov/pubmed/21781006
http://dx.doi.org/10.3109/15376516.2011.568983
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