Scientific Opinion on the safety and efficacy of vitamin K3 (menadione sodium bisulphite and menadione nicotinamide bisulphite) as a feed additive for all animal species

Feed, EFSA Panel on Additives and Products or Substances used in Animal

doi:10.2903/j.efsa.2014.3532

Cited by 16 publications

(10 citation statements)

References 50 publications

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“…Naphthoquinones, derived from naphthalenes, are the most commonly occurring quinones, many of which have known antifungal activities (26). Menadione is a synthetic heterocyclic naphthoquinone, also known as vitamin K3, which functions as the water-soluble analog of vitamin K (26,34). Plumbagin is a plant-derived naphthoquinone that has been studied for broad activity against cancer and pathogenic microbes (28,35).…”

Section: Resultsmentioning

confidence: 99%

Differential Roles of a Family of Flavodoxin-Like Proteins That Promote Resistance to Quinone-Mediated Oxidative Stress in Candida albicans

Foderaro

Konopka

2021

Infect Immun

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Survival of the fungal pathogen Candida albicans within a mammalian host relies on its ability to resist oxidative stress. The four flavodoxin-like proteins (PstI, PstII, Pst3, and Ycp4) that reside on the inner surface of the C. albicans plasma membrane represent a recently discovered antioxidant mechanism that is essential for virulence. Flavodoxin-like proteins combat oxidative stress by promoting a two-electron reduction of quinone molecules, which prevents formation of toxic semiquinone radicals. Previous studies indicated that Pst3 played a major role in promoting resistance to the small quinone molecules p-benzoquinone and menadione. Analysis of additional quinones confirmed this role for Pst3. To better define their function, antibodies were raised against each of the four flavodoxin-like proteins and used to quantify protein levels. Interestingly, the basal level of flavodoxin-like proteins differed, with Pst3 and Ycp4 being the most abundant. However, after induction with p-benzoquinone, PstI and Pst3 were the most highly induced, resulting in Pst3 becoming the most abundant. Constitutive expression of the flavodoxin-like protein genes from a TDH3 promoter resulted in similar protein levels and showed that PstI and Pst3 were better at protecting C. albicans against p-benzoquinone than PstII or Ycp4. In contrast, PstI and Ycp4 provided better protection against oxidative damage induced by tert-butyl hydroperoxide. Thus, both the functional properties and the relative abundance contribute to the distinct roles of the flavodoxin-like proteins in resisting oxidative stress. These results further define how C. albicans combats the host immune response and survives in an environment rich in oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Differential Roles of a Family of Flavodoxin-Like Proteins That Promote Resistance to Quinone-Mediated Oxidative Stress in Candida albicans

Foderaro

Konopka

2021

Infect Immun

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“…17 MSB has been widely used as an animal feed additive in Europe for a long time without a time limit. 18 It is considered as an adequate vitamin K resource to prevent animals' vitamin K deficiency. MSB is also intended for use in drinking water.…”

Section: ■ Introductionmentioning

confidence: 99%

Photoactive Water-Soluble Vitamin K: A Novel Amphiphilic Photoinduced Antibacterial Agent

Zhang

Wisuthiphaet

Nitin

et al. 2021

ACS Sustainable Chem. Eng.

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Menadione sodium bisulfite (MSB), also known as water-soluble vitamin K3 widely used as an animal food additive due to its low toxicity and low cost, is for the first time proven to be photoactive and antibacterial under various photoirradiation sources, evidenced by a computational modeling method and well-designed experiments. MSB demonstrates its robust photoactivity and application potential under ultraviolet A (UVA, 315–400 nm) irradiation. The results reveal that MSB could effectively generate reactive oxygen species (ROS) under UVA irradiation due to the formation of its oxidative triplet excited state. The photoinduced antibacterial tests also demonstrate the nonselective bacterial inactivation functions of MSB under proper photoirradiation. MSB was challenged against Gram-negative Escherichia coli (E. coli) and Gram-positive Listeria innocua (L. innocua) under UVA irradiation and exhibited excellent antibacterial performance (99.999% bacterial inactivation in 30 min of UVA exposure) in PBS. The antibacterial performance of MSB does not decay after five times of repeated exposures to bacteria and UVA irradiation, indicating the photostability and durability of MSB as a photoinduced antibacterial agent. More interestingly, solvents played a significant role in photoinduced antibacterial properties but not in the generation of ROS of MSB, indicating that the solvents may serve as contact media between MSB and bacteria cells. Intimate contact of MSB and microorganisms is thought of as a determinant in the bacterial inactivation by ROS or triplet excited states due to their relatively short lifetime and limited diffusion and function radius.

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“…TBT is an environmental contaminant known for its developmental toxicity, particularly in aquatic species, which also exerts endothelial cell toxicity (29–32). Menadione is a synthetic form of vitamin K, which is used as a nutritional and medicinal supplement in animals and sometimes in humans in low income countries (33) despite its well-known ability to stimulate oxidative stress in vitro (34–36) and a demonstrated toxicity toward endothelial cells (36, 37). To determine whether each individual ECFC clone can correctly distinguish a more potent chemical from its less potent counterpart, we selected four relatively nontoxic pairs to these toxicants.…”

Section: Introductionmentioning

confidence: 99%

“…To determine whether each individual ECFC clone can correctly distinguish a more potent chemical from its less potent counterpart, we selected four relatively nontoxic pairs to these toxicants. Specifically, we used ZnCl 2 as a relevant pair to CdCl 2 because the potential mechanism of Cd 2+ toxicity involves competition with Zn 2+ , an essential cofactor in proteins (38–41); sodium arsenate (or pentavalent As, Na 2 HAsO 4 ) as a less toxic counterpart to trivalent As (42–44); inorganic tin, SnCl 2 , as a less toxic counterpart of TBT (45, 46); and natural vitamin K1 (phytonadione) as a nontoxic matching pair to menadione (33).…”

Section: Introductionmentioning

confidence: 99%

Initial Assessment of Variability of Responses to Toxicants in Donor-Specific Endothelial Colony Forming Cells

Filonov

Tice

Luo

et al. 2018

Front. Public Health

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There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-forming cells (ECFCs) isolated from blood would be highly useful for this purpose because these cells are involved in neonatal and adult vasculogenesis. We characterized the cytotoxicity of four known toxic chemicals (NaAsO2, CdCl2, tributyltin [TBT], and menadione) and their four relatively nontoxic counterparts (Na2HAsO4, ZnCl2, SnCl2, and phytonadione, respectively) in eight ECFC clones representing four neonatal donors (2 male and 2 female donors, 2 clones per donor). ECFCs were exposed to 9 concentrations of each chemical in duplicate; cell viability was evaluated 48 h later using the fluorescent vital dye fluorescent dye 5-Carboxyfluorescein Diacetate (CFDA), yielding concentration-effect curves from each experiment. Technical (day-to-day) variability of the assay, assessed from three independent experiments, was low: p-values for the differences of results were 0.74 and 0.64 for the comparison of day 2 vs. day 1 and day 3 vs. day 1, respectively. The statistical analysis used to compare the entire concentration-effect curves has revealed significant differences in levels of cytotoxicity induced by the toxic and relatively nontoxic chemical counterparts, demonstrating that donor-specific ECFCs can clearly differentiate between these two groups of chemicals. Partitioning of the total variance in the nested design assessed the contributions of between-clone and between-donor variability for different levels of cytotoxicity. Individual ECFC clones demonstrated highly reproducible responses to the chemicals. The most toxic chemical was TBT, followed by NaAsO2, CdCl2, and Menadione. Nontoxic counterparts exhibited low cytotoxicity at the higher end of concentration ranges tested. Low variability was observed between ECFC clones obtained from the same donor or different donors for CdCl2, NaAsO2, and TBT, but for menadione, the between-donor variability was much greater than the between-clone variability. The low between-clone variability indicates that an ECFC clone may represent an individual donor in cell-based assays, although this finding must be confirmed using a larger number of donors. Such confirmation would demonstrate that an in vitro ECFC-based testing platform can be used to characterize the inter-individual variability of neonatal ECFCs exposed to drugs and/or environmental toxicants.

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Scientific Opinion on the safety and efficacy of vitamin K3 (menadione sodium bisulphite and menadione nicotinamide bisulphite) as a feed additive for all animal species

Cited by 16 publications

References 50 publications

Differential Roles of a Family of Flavodoxin-Like Proteins That Promote Resistance to Quinone-Mediated Oxidative Stress in Candida albicans

Differential Roles of a Family of Flavodoxin-Like Proteins That Promote Resistance to Quinone-Mediated Oxidative Stress in Candida albicans

Photoactive Water-Soluble Vitamin K: A Novel Amphiphilic Photoinduced Antibacterial Agent

Initial Assessment of Variability of Responses to Toxicants in Donor-Specific Endothelial Colony Forming Cells

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