The Relationship Between Vitamin B6, Diabetes and Cancer

Merigliano, Chiara; Mascolo, Elisa; Burla, Romina; Saggio, Isabella; Vernı̀, Fiammetta

doi:10.3389/fgene.2018.00388

Cited by 50 publications

(43 citation statements)

References 66 publications

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“…The major discovery of the present study is that VitB6 produces several beneficial effects to prevent inflammation in lung. Traditionally, VitB6 may treat depression, stroke, anaemia, nausea during pregnancy, clogged arteries, eye diseases, diabetes and inflammation associated with rheumatoid arthritis . Recently, we have identified that VitB6 improves insulin resistance in Apoe −/− mice fed with high‐fat diet and prevents isocarbophos‐induced vascular dementia in rats .…”

Section: Discussionmentioning

confidence: 99%

“…Traditionally, VitB6 may treat depression, stroke, anaemia, nausea during pregnancy, clogged arteries, eye diseases, diabetes and inflammation associated with rheumatoid arthritis. [28][29][30][31] Recently, we have identified that VitB6 improves insulin resistance in Apoe −/− mice fed with high-fat diet 32 and prevents isocarbophos-induced vascular dementia in rats. 33 Here, we further demonstrated that Mechanistically, we uncovered that the AMPK-DOK3 pathway contributes to the anti-inflammatory effects of VitB6 by inhibiting macrophage activation.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Shan

Zhou

et al. 2020

J Cellular Molecular Medi

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Macrophage activation participates in the pathogenesis of pulmonary inflammation. As a coenzyme, vitamin B6 (VitB6) is mainly involved in the metabolism of amino acids, nucleic acids, glycogen and lipids. We have previously reported that activation of AMP‐activated protein kinase (AMPK) produces anti‐inflammatory effects both in vitro and in vivo. Whether VitB6 via AMPK activation prevents pulmonary inflammation remains unknown. The model of acute pneumonia was induced by injecting mice with lipopolysaccharide (LPS). The inflammation was determined by measuring the levels of interleukin‐1 beta (IL‐1β), IL‐6 and tumour necrosis factor alpha (TNF‐α) using real time PCR, ELISA and immunohistochemistry. Exposure of cultured primary macrophages to VitB6 increased AMP‐activated protein kinase (AMPK) Thr172 phosphorylation in a time/dose‐dependent manner, which was inhibited by compound C. VitB6 downregulated the inflammatory gene expressions including IL‐1β, IL‐6 and TNF‐α in macrophages challenged with LPS. These effects of VitB6 were mirrored by AMPK activator 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR). However, VitB6 was unable to inhibit LPS‐induced macrophage activation if AMPK was in deficient through siRNA‐mediated approaches. Further, the anti‐inflammatory effects produced by VitB6 or AICAR in LPS‐treated macrophages were abolished in DOK3 gene knockout (DOK3−/−) macrophages, but were enhanced in macrophages if DOK3 was overexpressed. In vivo studies indicated that administration of VitB6 remarkably inhibited LPS‐induced both systemic inflammation and acute pneumonia in wild‐type mice, but not in DOK3−/− mice. VitB6 prevents LPS‐induced acute pulmonary inflammation in mice via the inhibition of macrophage activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Shan

Zhou

et al. 2020

J Cellular Molecular Medi

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“…In addition PLP acts as a modulator of steroid hormone receptor‐mediated gene expression (di Salvo, Contestabile, & Safo, ) and it is able to quench reactive oxygen species (ROS) and advanced glycation end products (AGEs) (Bilski, Li, Ehrenshaft, Daub, & Chignell, ). Based on its wide range of functions it is not surprising that PLP is beneficial for many human diseases such as schizophrenia, epilepsy, Alzheimer's disease, Parkinson's disease, malaria, diabetes, and cancer (di Salvo, Safo, & Contestabile, ; Merigliano, Mascolo, Burla, Saggio, & Verni, ).…”

Section: Introductionmentioning

confidence: 99%

Pyridoxine/pyridoxamine 5′‐phosphate oxidase (Sgll/PNPO) is important for DNA integrity and glucose homeostasis maintenance in Drosophila

Mascolo

Amoroso

Saggio

et al. 2019

Journal Cellular Physiology

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Pyridoxine/pyridoxamine 5′-phosphate oxidase (PNPO) and pyridoxal kinase (PDXK) cooperate to produce pyridoxal 5′-phosphate (PLP), the active form of vitamin B6. PDXK phosphorylates pyridoxine, pyridoxamine, and pyridoxal by producing PNP, PMP, and PLP, whereas PNPO oxidizes PNP, PMP, into PLP. We previously demonstrated that PDXK depletion in Drosophila and human cells impacts on glucose metabolism and DNA integrity.Here we characterized sgll, the Drosophila ortholog of PNPO gene, showing that its silencing by RNA interference elicits chromosome aberrations (CABs) in brains and induces diabetic hallmarks such as hyperglycemia and small body size. We showed that in sgll RNAi neuroblasts CABs are largely produced by the genotoxic effect of the advanced glycation end products triggered by high glucose. As in sgll RNAi cells, part of PLP is still produced by PDXK activity, these data suggest that PLP dosage need to be tightly regulated to guarantee glucose homeostasis and DNA integrity. K E Y W O R D S chromosome aberrations, diabetes, Drosophila, sgll/PNPO, vitamin B6

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“…For this reason, the present study focuses specifically on this form of vitamin B 6 to shed new light on one of the possible mechanisms underlying this inhibitory activity. The other two forms have also been reported to show antioxidant activity [66,67] and the aforementioned study on the ROS trapping ability of PN [28] shows that it shares some of the preferred reaction sites with PM (namely, the phenol group, the methylene moieties and the aromatic carbons adjacent to the pyridine nitrogen). Since PLP also displays all these structural elements, it is plausible that it also scavenges ROS by similar mechanisms.…”

Section: Discussionmentioning

confidence: 96%

How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity

et al. 2019

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Pyridoxamine, one of the natural forms of vitamin B 6 , is known to be an effective inhibitor of the formation of advanced glycation end products (AGEs), which are closely related to various human diseases. Pyridoxamine forms stable complexes with metal ions that catalyze the oxidative reactions taking place in the advanced stages of the protein glycation cascade. It also reacts with reactive carbonyl compounds generated as byproducts of protein glycation, thereby preventing further protein damage. We applied Density Functional Theory to study the primary antioxidant activity of pyridoxamine towards three oxygen-centered radicals (•OOH, •OOCH 3 and •OCH 3 ) to find out whether this activity may also play a crucial role in the context of protein glycation inhibition. Our results show that, at physiological pH, pyridoxamine can trap the •OCH 3 radical, in both aqueous and lipidic media, with rate constants in the diffusion limit (>1.0 × 10 8 M −1 s −1 ). The quickest pathways involve the transfer of the hydrogen atoms from the protonated pyridine nitrogen, the protonated amino group or the phenolic group. Its reactivity towards •OOH and •OOCH 3 is smaller, but pyridoxamine can still scavenge them with moderate rate constants in aqueous media. Since reactive oxygen species are also involved in the formation of AGEs, these results highlight that the antioxidant capacity of pyridoxamine is also relevant to explain its inhibitory role on the glycation process.Given the pathological implications of protein glycation, the design of molecules with the ability to attenuate its effects is a matter of utmost concern. The three main mechanisms by which these molecules, known as protein glycation inhibitors, prevent the formation of AGEs are: (i) the complexation of metal ions that catalyze the secondary reactions of protein glycation; (ii) the scavenging of RCS; and (iii) ROS generated as byproducts of those secondary reactions. In 1999, it was discovered that pyridoxamine (PM) had the ability of inhibiting the oxidation of Amadori compounds to form AGEs [10]. PM is one of the three natural forms of vitamin B 6 , together with pyridoxal (PL) and pyridoxine (PN). By that time, it was known that PM was very reactive towards carbonyl groups, since it acted as a coenzyme in transamination reactions between carbonyl compounds and amino groups [11], and this led to consider that it could be an effective AGE inhibitor. Thus far, several studies in both animal and human models have shown its therapeutic effects on diabetic kidney disease [12,13], as well as on retinopathies [14] and vascular diseases [15].Concerning its mechanism of action, it has been suggested that PM could be effective as a metal chelating agent, a RCS scavenger and/or a ROS scavenger. It can form stable complexes with Cu 2+ and Fe 3+ [16,17] and stable adducts with several dicarbonyl compounds [18][19][20][21], as well as inhibit the production of the hydroxyl radical from the Fenton reaction or directly react with it [22][23][24]. Some studies also suggest that ...

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The Relationship Between Vitamin B6, Diabetes and Cancer

Cited by 50 publications

References 66 publications

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Pyridoxine/pyridoxamine 5′‐phosphate oxidase (Sgll/PNPO) is important for DNA integrity and glucose homeostasis maintenance in Drosophila

How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity

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