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Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk for heart failure, yet preventive cardiac care is suboptimal in this population. Pyridoxamine (PM), a vitamin B6 analog, has been shown to exert protective effects in metabolic and cardiovascular diseases. In this study, we aimed to investigate whether PM limits adverse cardiac remodeling and dysfunction in rats who develop T2DM. Male rats received a standard chow diet or Western diet (WD) for 18 weeks to induce prediabetes. One WD group received additional PM (1 g/L) via drinking water. Glucose tolerance was assessed with a 1 h oral glucose tolerance test. Cardiac function was evaluated using echocardiography and hemodynamic measurements. Histology on left ventricular (LV) tissue was performed. Treatment with PM prevented the increase in fasting plasma glucose levels compared to WD-fed rats (p < 0.05). LV cardiac dilation tended to be prevented using PM supplementation. In LV tissue, PM limited an increase in interstitial collagen deposition (p < 0.05) seen in WD-fed rats. PM tended to decrease 3-nitrotyrosine and significantly lowered 4-hydroxynonenal content compared to WD-fed rats. We conclude that PM alleviates interstitial fibrosis and oxidative stress in the hearts of WD-induced prediabetic rats. [ABSTRACT FROM AUTHOR]

AIM: To determine whether the microRNA-27b-3p (miR-27b-3p)/NF-E2-related factor 2 (Nrf2) pathway plays a role in human retinal pigment epithelial (hRPE) cell response to high glucose, how miR-27b-3p and Nrf2 expression are regulated, and whether this pathway could be specifically targeted. METHODS: hRPE cells were cultured in normal glucose or high glucose for 1, 3, or 6d before measuring cellular proliferation rates using cell counting kit-8 and reactive oxygen species (ROS) levels using a dihydroethidium kit. miR-27b-3p, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) mRNA and protein levels were analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunocytofluorescence (ICF), respectively. Western blot analyses were performed to determine nuclear and total Nrf2 protein levels. Nrf2, NQO1, and HO-1 expression levels by RT-qPCR, ICF, or Western blot were further tested after miR-27b-3p overexpression or inhibitor lentiviral transfection. Finally, the expression level of those target genes was analyzed after treating hRPE cells with pyridoxamine. RESULTS: Persistent exposure to high glucose gradually suppressed hRPE Nrf2, NQO1, and HO-1 mRNA and protein levels and increased miR-27b-3p mRNA levels. High glucose also promoted ROS release and inhibited cellular proliferation. Nrf2, NQO1, and HO-1 mRNA levels decreased after miR-27b-3p overexpression and, conversely, both mRNA and protein levels increased after expressing a miR-27b-3p inhibitor. After treating hRPE cells exposed to high glucose with pyridoxamine, ROS levels tended to decreased, proliferation rate increased, Nrf2, NQO1, and HO-1 mRNA and protein levels were upregulated, and miR-27b-3p mRNA levels were suppressed. CONCLUSION: Nrf2 is a downstream target of miR-27b-3p. Furthermore, the miR-27b-3p inhibitor pyridoxamine can alleviate high glucose injury by regulating the miR-27b-3p/Nrf2 axis.

Doxorubicin (DOX) is commonly used in cancer treatment but associated with cardiotoxicity. Pyridoxamine (PM), a vitamin B6 derivative, could be a cardioprotectant. This study investigated the effect of PM on DOX cardiotoxicity and DOX antitumor effectiveness. Sprague Dawley rats were treated intravenously with DOX (2 mg/kg/week) or saline over eight weeks. Two other groups received PM via oral intake (1 g/L in water bottles) next to DOX or saline. Echocardiography was performed after eight weeks. PM treatment significantly attenuated the DOX-induced reduction in left ventricular ejection fraction (72 ± 2% vs. 58 ± 3% in DOX; p < 0.001) and increase in left ventricular end-systolic volume (0.24 ± 0.02 µL/cm2 vs. 0.38 ± 0.03 µL/cm2 in DOX; p < 0.0001). Additionally, LA7 tumor cells were exposed to DOX, PM, or DOX and PM for 24 h, 48 h, and 72 h. Cell viability, proliferation, cytotoxicity, and apoptosis were assessed. DOX significantly reduced LA7 cell viability and proliferation (p < 0.0001) and increased cytotoxicity (p < 0.05) and cleaved caspase-3 (p < 0.001). Concomitant PM treatment did not alter the DOX effect on LA7 cells. In conclusion, PM attenuated DOX-induced cardiomyopathy in vivo without affecting the antitumor effect of DOX in vitro, highlighting PM as a promising cardioprotectant for DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

The use of doxorubicin (DOX) chemotherapy is restricted due to dose-dependent cardiotoxicity. Pyridoxamine (PM) is a vitamin B6 derivative with favorable effects on diverse cardiovascular diseases, suggesting a cardioprotective effect on DOX-induced cardiotoxicity. The cardioprotective nature of PM was investigated in a rat model of DOX-induced cardiotoxicity. Six-week-old female Sprague Dawley rats were treated intravenously with 2 mg/kg DOX or saline (CTRL) weekly for eight weeks. Two other groups received PM via the drinking water next to DOX (DOX+PM) or saline (CTRL+PM). Echocardiography, strain analysis, and hemodynamic measurements were performed to evaluate cardiac function. Fibrotic remodeling, myocardial inflammation, oxidative stress, apoptosis, and ferroptosis were evaluated by various in vitro techniques. PM significantly attenuated DOX-induced left ventricular (LV) dilated cardiomyopathy and limited TGF-β1-related LV fibrotic remodeling and macrophage-driven myocardial inflammation. PM protected against DOX-induced ferroptosis, as evidenced by restored DOX-induced disturbance of redox balance, improved cytosolic and mitochondrial iron regulation, and reduced mitochondrial damage at the gene level. In conclusion, PM attenuated the development of cardiac damage after DOX treatment by reducing myocardial fibrosis, inflammation, and mitochondrial damage and by restoring redox and iron regulation at the gene level, suggesting that PM may be a novel cardioprotective strategy for DOX-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Ovarian advanced glycation end-products (AGEs) accumulation is associated with ovarian granulosa cells (GCs) dysfunction. Vitamin B6 derivatives positively affected reproduction. The current study was conducted to elucidate the AGEs effects on human luteinized mural GCs steroidogenesis in the presence or absence of pyridoxamine (PM). Methods and results: Isolated GCs of 50 healthy women were divided into four parts and treated with media alone (Control), PM alone, or human glycated albumin (HGA) with/without PM. Main steroidogenic enzymes and hormones were assessed by qRT-PCR and ELISA. The AGE receptor (RAGE) protein was also determined using Western blotting. The non-toxic concentration of HGA increased the expression of RAGE, StAR, 3β-HSD, and 17β-HSD (P < 0.0001 for all) but decreased the expression of CYP19A1 at mRNA levels. The increased RAGE protein expression was also confirmed by western blot analysis. These effects resulted in declined estradiol (E2), slightly, and a sharp rise in progesterone (P4) and testosterone (T) levels, respectively. PM, on its own, ameliorated the HGA-altered enzyme expression and, thereby, corrected the aberrant levels of E2, P4, and T. These effects are likely mediated by regulating the RAGE gene and protein expression. Conclusion: This study indicates that hormonal dysfunctions induced by the AGEs-RAGE axis in luteinized GCs are likely rectified by PM treatment. This effect is likely acquired by reduced expression of RAGE. A better understanding of how AGEs and PM interact in ovarian physiology and pathology may lead to more targeted therapy for treating ovarian dysfunction. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest‐observed‐effect‐level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a case–control study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2–2.5 mg/day (4–11 months), 3.2–4.5 mg/day (1–6 years), 6.1–10.7 mg/day (7–17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of pyridoxamine (PM), a B6 vitamer and dicarbonyl scavenger, on glycation and a large panel of metabolic and vascular measurements in a randomized double‐blind placebo‐controlled trial in abdominally obese individuals. Materials and methods: Individuals (54% female; mean age 50 years; mean body mass index 32 kg/m2) were randomized to an 8‐week intervention with either placebo (n = 36), 25 mg PM (n = 36) or 200 mg PM (n = 36). We assessed insulin sensitivity, β‐cell function, insulin‐mediated microvascular recruitment, skin microvascular function, flow‐mediated dilation, and plasma inflammation and endothelial function markers. PM metabolites, dicarbonyls and advanced glycation endproducts (AGEs) were measured using ultra‐performance liquid chromatography tandem mass spectrometry. Treatment effects were evaluated by one‐way ANCOVA. Results: In the high PM dose group, we found a reduction of plasma methylglyoxal (MGO) and protein‐bound Nδ‐(5‐hydro‐5‐methyl‐4‐imidazolon‐2‐yl)‐ornithine (MG‐H1), as compared to placebo. We found a reduction of the endothelial dysfunction marker soluble vascular cell adhesion molecule‐1 (sVCAM‐1) in the low and high PM dose group and of soluble intercellular adhesion molecule‐1 (sICAM‐1) in the high PM dose, as compared to placebo. We found no treatment effects on insulin sensitivity, vascular function or other functional outcome measurements. Conclusions: This study shows that PM is metabolically active and reduces MGO, AGEs, sVCAM‐1 and sICAM‐1, but does not affect insulin sensitivity and vascular function in abdominally obese individuals. The reduction in adhesion markers is promising because these are important in the pathogenesis of endothelial damage and atherosclerosis. [ABSTRACT FROM AUTHOR]

The use of doxorubicin (DOX) chemotherapy is restricted due to dose-dependent cardiotoxicity. Pyridoxamine (PM) is a vitamin B6 derivative with favorable effects on diverse cardiovascular diseases, suggesting a cardioprotective effect on DOX-induced cardiotoxicity. The cardioprotective nature of PM was investigated in a rat model of DOX-induced cardiotoxicity. Six-week-old female Sprague Dawley rats were treated intravenously with 2 mg/kg DOX or saline (CTRL) weekly for eight weeks. Two other groups received PM via the drinking water next to DOX (DOX+PM) or saline (CTRL+PM). Echocardiography, strain analysis, and hemodynamic measurements were performed to evaluate cardiac function. Fibrotic remodeling, myocardial inflammation, oxidative stress, apoptosis, and ferroptosis were evaluated by various in vitro techniques. PM significantly attenuated DOX-induced left ventricular (LV) dilated cardiomyopathy and limited TGF-β1-related LV fibrotic remodeling and macrophage-driven myocardial inflammation. PM protected against DOX-induced ferroptosis, as evidenced by restored DOX-induced disturbance of redox balance, improved cytosolic and mitochondrial iron regulation, and reduced mitochondrial damage at the gene level. In conclusion, PM attenuated the development of cardiac damage after DOX treatment by reducing myocardial fibrosis, inflammation, and mitochondrial damage and by restoring redox and iron regulation at the gene level, suggesting that PM may be a novel cardioprotective strategy for DOX-induced cardiomyopathy.

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old control mice, but was maintained in pyridoxamine treated mice. Large artery stiffness decreased in pyridoxamine-treated mice but was unaffected in control mice. Pyridoxamine-treated mice had greater cerebral artery endothelium-dependent dilation compared with old control mice, and not different from young mice. Old control mice had impaired cognitive function; however, pyridoxamine only partially preserved cognitive function in old mice. In summary, pyridoxamine treatment in old mice prevented age-related increases in blood pressure, reduced large artery stiffness, preserved cerebral artery endothelial function, and partially preserved cognitive function. Taken together, these results suggest that pyridoxamine treatment may limit vascular aging. [ABSTRACT FROM AUTHOR]

Vitamin B6 is defined as the sum of pyridoxal, pyridoxine and pyridoxamine vitamers. The content of each form is quite different in various types of vegetables. This investigation aimed to determine the amount and bioaccessibility of pyridoxal, pyridoxine and pyridoxamine vitamers of vitamin B6 in various vegetables. In the study, it was determined that the total vitamin B6 content in various vegetables (carrots, broccoli, brussels sprouts, zucchini, potatoes, cucumbers, red pepperoni, tomatoes, chard, green peppers, parsley, spinach, onions, green beans, leek and curly lettuce) ranged from 0.25 mg·kg-1 to 5.93 mg·kg-1. The average proportion of pyridoxal, pyridoxine and pyridoxamine forms in vegetables was 25.9 %, 50.3 %, and 23.8 %, respectively. However, these proportions were 34.7 %, 34.7 % and 14.8 % in green leafy vegetables. The bioaccessibility of total vitamin B6 in samples ranged from 17 % to 69 %, and the average bioaccessibility of pyridoxal, pyridoxine and pyridoxamine vitamers was 43 %, 34 % and 51 %, respectively. The lowest and highest average bioaccessibility was determined for pyridoxine and pyridoxamine vitamers, respectively. [ABSTRACT FROM AUTHOR]

Context: Type 2 diabetes (T2D) patients have reduced bone turnover and increased fractures. Advanced glycation endproducts (AGEs) impair osteoblasts and are implicated in diabetic fractures. Pyridoxamine (PM) is a vitamin B6 metabolite which inhibits formation of AGEs., Objective: We hypothesized that PM treatment in older T2D patients, by inhibiting AGEs, would increase bone formation., Design: Double-blind RCT., Setting: Academic center., Participants: Older T2D women (n=55)., Intervention: Oral PM 200 mg twice daily for one year., Main Outcomes: The primary outcome was the change in the bone formation marker P1NP. Other outcomes were changes in bone resorption, bone mineral density (BMD), HbA1c and skin autofluorescence (SAF), and in a bone biopsy sub-group, the correlation between bone fluorescent AGEs (fAGEs) and SAF., Results: P1NP increased 23.0% with PM (95% CI: 9, 37; within-group p=0.028) vs. 4.1% with placebo (-9, 17; within-group p=0.576; between-groups p=0.056). BMD increased at the femoral neck (PM: 2.6±5% vs. placebo: -0.9±4%; between-groups p=0.007). Bone resorption markers and SAF did not change. HbA1c decreased (PM: -0.38 ± 0.7% vs. placebo: 0.05 ± 1.7%; between-groups p =0.04). Within the PM group, the HbA1c change correlated inversely with the % P1NP change (r =-0.50, p=0.034). Cortical bone biopsy fAGEs correlated with SAF (r=0.86, p=0.001). Adverse events were similar between groups., Conclusion: PM tended to increase P1NP in older T2D women, as well as increasing bone density and reducing HbA1c. Further studies are needed to investigate the potential of PM as a disease mechanism-directed approach to reduce fractures in T2D., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO‐induced dysfunction. We observed that the accumulation of MGO‐derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO‐derived AGEs in the wound tissue of type‐2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1‐like macrophages induced by lipopolysaccharide (LPS), but not those of M0‐like macrophages induced by PMA or of M2‐like macrophages induced by interleukins 4 (IL‐4) and 13 (IL‐13); the impaired phagocytosis of M1‐like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non‐healing diabetic wounds. [ABSTRACT FROM AUTHOR]

B6 vitamers are important natural compounds for human life, principally for amino acid metabolism, and have been reported as potent scavenger molecules of both endogenous and exogenous reactive oxygen species (ROS). However, under UV-light excitation from UVC (200–280 nm) to UVA (315–400 nm), B6 vitamers act as endogenous photosensitizers that promote both cellular photodamage and enzyme inactivation. This occurs through classical photochemical mechanisms mediated by ROS, toxic photoproducts, and the formation of adducts with active protein sites. This minireview aimed to present and discuss the dual roles of B6 vitamers as generators and scavengers of singlet oxygen (an important reactive species in photodynamic processes) and various other ROS. We also examine the basic photophysical, photochemical, and protolytic equilibria principles of B6 vitamers and their role as photodamaging and photoprotecting compounds in UV-light mediated photobiological processes.

Raquel Rangel Silvares1,*, Evelyn Nunes Goulart da Silva Pereira1,*, Edgar Eduardo Ilaquita Flores1, Karine Lino Rodrigues1, Adriana Ribeiro Silva2, Cassiano Felipe Gonçalves-de-Albuquerque2,3, Anissa Daliry1 1Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; 2Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; 3Laboratory of Immunopharmacology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil*These authors contributed equally to this workCorrespondence: Anissa DaliryInstituto Oswaldo Cruz, Fiocruz, Pavilhão Ozório de Almeida, Manguinhos, Rio de Janeiro, CEP: 21.040-360, RJ, BrazilEmail daliry@ioc.fiocruz.brIntroduction: This study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction.Methodology: In Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1β). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression.Results: Wistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1β were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFD-induced MetS rats in comparison to CTLs.Conclusions: Our findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage.Keywords: metabolic syndrome, kidney endothelial dysfunction, pyridoxamine, advanced glycation end products

Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their phosphorylated derivatives including the biological active pyridoxal 5′-phosphate (PLP). While PN toxicity is known to complicate several treatments, PM has shown promise in relation to the treatment of metabolic and age-related diseases by blocking oxidative degradation and scavenging toxic dicarbonyl compounds and reactive oxygen species. We aimed to assess the metabolization of oral PM supplements in a single and three daily dose. We optimized and validated a method for the quantification of the B6 vitamers in plasma and urine using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five healthy volunteers were recruited to study PM metabolization after a single oral dose of 200 mg PM or a three daily dose of 67 mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, 24 h urine and fasted second void urine samples were collected. After a single oral dose of 200 mg PM, plasma PM increased in the first 3 h to a maximum of 2324 ± 266 nmol/L. While plasma PM levels returned to baseline after ~10 h of PM intake, PLP increased to a maximum of 2787 ± 329 nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5 ± 2.1 nmol/L; it was nearly undetectable after ~12 h. With a three daily dose of 67 mg PM we observed an increase and decline of plasma PM, PL, and PN concentrations after each PM intake. PLP showed a similar increase as in the single dose protocol and accumulated over time. In this study we showed high plasma levels of PM after oral PM supplementation. We found steadily increasing levels of the biologically active PLP, with minimal formation of PN. The B6 vitamer PM is an interesting supplement as an inhibitor of harmful processes in metabolic diseases and for the treatment of vitamin B6 deficiency. The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588. [ABSTRACT FROM AUTHOR]

High plasma levels of the sphingolipid intermediates ceramide (Cer) and sphingosine-1-phosphate (S1P) are suggested to be involved in the development of insulin resistance (IR). Recent evidence indicates that advanced glycation endproducts (AGEs) can alter the sphingolipids metabolism equilibrium. Since enzymes responsible for sphingolipid rheostat maintenance are highly expressed in liver, we thus investigated whether AGEs accumulation can affect hepatic sphingolipids metabolism in insulin resistant mice. Two different models of IR were examined: genetically diabetic LeptrDb-/- (DbDb) and diet-induced insulin resistant C57Bl/6J mice fed a 60% trans -fat diet (HFD). In addition, a group of HFD mice was supplemented with the anti-AGEs compound pyridoxamine. AGEs were evaluated in the liver by western blotting. Cer and S1P were measured by UHPLC-MS/MS. The expression of RAGE and of enzymes involved in sphingolipid metabolism were assessed by RT-PCR and western blotting. HepG2 cells were used to study the effect of the major AGE Nε-(carboxymethyl)lysine (CML)-albumin on sphingolipid metabolism and the role of the receptor of AGEs (RAGE). High levels of AGEs and RAGE were detected in the liver of both DbDb and HFD mice in comparison to controls. The expression of enzymes of sphingolipid metabolism was altered in both models, accompanied by increased levels of Cer and S1P. Specifically, ceramide synthase 5 and sphingosine kinase 1 were increased, while neutral ceramidase was reduced. Pyridoxamine supplementation to HFD mice diminished hepatic AGEs and prevented alterations of sphingolipid metabolism and the development of IR. CML administration to HepG2 cells evoked alterations similar to those observed in vivo , that were in part mediated by the binding to RAGE. The present study shows a direct involvement of AGEs in alterations of sphingolipid metabolism associated to the development of IR. The modulation of sphingolipids metabolism through the prevention of AGEs accumulation by pyridoxamine may reduce the development of IR. [Display omitted] • In insulin resistant mice sphingolipid rheostat and related enzymes are compromised. • AGEs accumulation in liver is associated to impaired sphingolipid metabolism. • AGE/RAGE signalling is in part responsible for altered enzymes expression. • Inhibition of AGEs production by pyridoxamine prevents sphingolipids alterations. • Inhibition of AGEs production by pyridoxamine prevents insulin resistance. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to examine the effect of a diet intervention and pyridoxamine (PM) supplementation on hepatic microcirculatory and metabolic dysfunction in nonalcoholic fatty liver disease (NAFLD). Methods: NAFLD in Wistar rats was induced with a high-fat diet for 20 weeks (NAFLD 20 weeks), and control animals were fed with a standard diet. The NAFLD diet intervention group received the control diet between weeks 12 and 20 (NAFLD 12 weeks), while the NAFLD 12 weeks + PM group also received PM. Fasting blood glucose (FBG) levels, body weight (BW), visceral adipose tissue (VAT), and hepatic microvascular blood flow (HMBF) were evaluated at the end of the protocol. Results: The NAFLD group exhibited a significant increase in BW and VAT, which was prevented by the diet intervention, irrespective of PM treatment. The FBG was elevated in the NAFLD group, and caloric restriction improved this parameter, although additional improvement was achieved by PM. The NAFLD group displayed a 31% decrease in HMBF, which was partially prevented by caloric restriction and completely prevented when PM was added. HMBF was negatively correlated to BW, FBG, and VAT content. Conclusion: PM supplementation in association with lifestyle modifications could be an effective intervention for metabolic and hepatic vascular complications. [ABSTRACT FROM AUTHOR]

AIM: To observe the effects of pyridoxamine(PM)on RAGE, ROS and apoptosis in RPE cells treated with advanced glycation end products(AGEs), and to investigate the protective effect of PM on RPE cells in diabetic retinopathy. METHODS:Primary cultured human RPE cells, the third generation of cells were synchronized with serum-free Dulbecco-modified Eagle medium for 24h, and then grouped: 1)Control group: cultured with 100mg/L BSA for 48h; 2)AGEs-treated group: cultured with 200mg/L AGEs for 48h; 3)PM group: PM1 group: cultured with 16mg/L PM+200mg/L AGEs for 48h; PM2 group: cultured with 32mg/L PM+200mg/L AGEs for 48h. The expression of RAGE protein was detected by immunohistochemistry. The formation of ROS was observed by fluorescence microscopy. The apoptosis of cells was detected by TUNEL. RESULTS:The expression of RAGE protein, ROS and apoptosis of RPE cells in PM group were significantly lower than those in AGEs-treated group, and decreased with the increase of PM concentration. CONCLUSION:Pyridoxamine can inhibit the expression of RAGE and the production of ROS, reduce apoptosis, and have a protective effect on RPE cells.

The amount of vitamin B6 in foods is reported in the literature as the sum of the pyridoxal (PL), pyridoxamine (PM), and pyridoxine (PN) forms. The levels of the PL, PM, and PN forms of vitamin B6 are different from each other. The aim of the present study was to reveal how cooking methods affect PL, PM, and PN levels in cooked fish samples. Therefore, the widely consumed fish species European anchovy (Engraulis encrasicolus), gilthead seabream (Sparus aurata), and Atlantic bonito (Sarda sarda) were cooked using grilling and baking techniques. The measurable PN amount was negligible. However, significant destruction of both PL and PM in all cooked fishes was detected. The loss in PL ranged from 54 to 97%, while the loss in PM was between 19 and 78%. The loss of PL in baked Atlantic bonito (97%) was significantly higher than in the other fish samples (p <.05). The cooking loss of total vitamin B6 in anchovy, gilthead seabream, and Atlantic bonito was 64, 55, and 85% when grilled and 61, 60, and 89% when baked, respectively. [ABSTRACT FROM AUTHOR]

Vitamin B6 comprises an important set of molecules tightly interwoven with the human amino acid, fatty acid, and carbohydrate metabolism. Analytical methods striving for the quantification of individual B6 vitamers so far mostly rely on methods based on HPLC in combination with fluorescence detection, but their application encounters multiple difficulties due to the chemical divergence of the single vitamers. The present study describes the development of a method based on LC-MS/MS and stable isotope dilution assay (SIDA) for the simultaneous quantification of five vitamers (PN, PL, PM, PMP, and PNG) of the B6 group in food samples. [13C3]-PN, [13C3]-PL, and [13C6]-PNG were applied as internal standards for the analysis of PN, PL, and PNG. PM and PMP were quantified via matrix-matched calibration referring to [13C3]-PN. The developed method was validated using starch matrix. The limits of detection and quantification ranged from 0.0028 to 0.02 mg/kg and from 0.0085 to 0.059 mg/kg, respectively, for all analytes. Calculated recoveries varied from 92 to 111%. Intra-injection precisions ranged from 0 to 9%, inter-day precisions from 4 to 10%, and intra-day precisions from 4 to 10%. A total of 14 plant-based food samples including fruits, vegetables, and cereals were examined for their content of vitamin B6 using the validated method. Furthermore, the first quantitation of PNG without enzymatic steps or divergent internal standards was undertaken utilizing LC-MS/MS and SIDA. [ABSTRACT FROM AUTHOR]

Diabetic neuropathic pain is a common complication of diabetes mellitus and requires a substantial amount of societal resources. Pyridoxamine is an inhibitor of advanced glycation and lipoxidation end products. Several animal and clinical studies have confirmed that pyridoxamine can inhibit a range of pathological changes in diabetes-induced organ injury and alleviate certain kinds of neuropathic pain. However, no studies have attempted to explore the effects of pyridoxamine on diabetic neuropathic pain. We conducted animal experiments to examine whether pyridoxamine could alleviate diabetic neuropathic pain and to explore the mechanism underlying these effects. Adult male Sprague Dawley rats were randomly assigned to the normal + sterile water group, diabetic + sterile water group, diabetic + pyridoxamine100 group, diabetic +pyridoxamine200 group, diabetic + pyridoxamine400 group, or normal + pyridoxamine group. The rats in the diabetic +pyridoxamine100, diabetic + pyridoxamine200, diabetic + pyridoxamine400, and normal + pyridoxamine groups received pyridoxamine at dosages of 100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day, and 400 mg/kg/day, respectively, via intragastric administration. The rats in the other groups received water daily. Pyridoxamine alleviated diabetic neuropathic pain at least partially by suppressing the activity of the spinal receptor for advanced glycation end products-nuclear factor-κB/extracellular signal-regulated kinase signaling pathway; additionally, pyridoxamine decreased advanced glycation end product-modified low-density lipoprotein, oxidized low-density lipoprotein, and interleukin-1β levels in the serum. The immunofluorescence staining results revealed that most phosphorylated nuclear factor-κB was localized to neuronal cells and not to microglia or astrocytes; this pattern may be associated with the upregulated expression of pain-related proteins. The abovementioned results indicate that pyridoxamine is a promising choice for the clinical treatment of diabetic neuropathic pain. Further investigations need to be carried out to confirm the benefits of pyridoxamine. [ABSTRACT FROM AUTHOR]

Objective: We investigated the protective effects of pyridoxamine against metabolic and microcirculatory complications in nonalcoholic fatty liver disease. Methods: Nonalcoholic fatty liver disease was established by a high‐fat diet administration over 28 weeks. Pyridoxamine was administered between weeks 20 and 28. The recruitment of leukocytes and the number of vitamin A‐positive hepatic stellate cells were examined by in vivo microscopy. Laser speckle contrast imaging was used to evaluate microcirculatory hepatic perfusion. Thiobarbituric acid reactive substances measurement and RT‐PCR were used for oxidative stress and inflammatory parameters. advanced glycation end products were evaluated by fluorescence spectroscopy. Results: The increase in body, liver, and fat weights, together with steatosis and impairment in glucose metabolism observed in the nonalcoholic fatty liver disease group were attenuated by pyridoxamine treatment. Regarding the hepatic microcirculatory parameters, rats with high‐fat diet‐induced nonalcoholic fatty liver disease showed increased rolling and adhesion of leukocytes, increased hepatic stellate cells activation, and decreased tissue perfusion, which were reverted by pyridoxamine. Pyridoxamine protected against the increased hepatic lipid peroxidation observed in the nonalcoholic fatty liver disease group. Pyridoxamine treatment was associated with increased levels of tumor necrosis factor alpha (TNF‐α) mRNA transcripts in the liver. Conclusion: Pyridoxamine modulates oxidative stress, advanced glycation end products, TNF‐α transcripts levels, and metabolic disturbances, being a potential treatment for nonalcoholic fatty liver disease‐associated microcirculatory and metabolic complications. [ABSTRACT FROM AUTHOR]

Neonatal epileptic encephalopathy (NEE), as a result of pyridoxine 5′-phosphate oxidase (PNPO) deficiency, is a rare neural disorder characterized by intractable seizures and usually leads to early infant death. The clinical phenotypes do not respond to antiepileptic drugs but are alleviated in most cases by giving large doses of pyridoxal 5′-phosphate (PLP). PLP is the active form of vitamin B6 participating in more than 100 enzymatic pathways. One of the causes of NEE is pathogenic mutations in the gene for human PNPO (hPNPO). PNPO is a key enzyme in converting pyridoxine (PN), the common dietary form of vitamin B6, and some other B6 vitamers to PLP. More than 25 different mutations in hPNPO, which result in reduced catalytic activity, have been described for PNPO-deficiency NEE. To date, no animal model is available to test new therapeutic strategies. In this report, we describe using zebrafish with reduced activity of Pnpo as an animal model. Knocking down zPnpo resulted in developmental anomalies including brain malformation and impaired locomotor activity, similar to the clinical features of PNPO-deficiency NEE. Other anomalies include a defective circulation system. These anomalies were significantly alleviated by co-injecting either zpnpo or hPNPO mRNAs. As expected from clinical observations in humans, supplementing with PLP improved the morphological and behavioral anomalies. PN only showed marginal positive effects, and only in a few anomalies. Remarkably, pyridoxamine (PM), another dietary form of vitamin B6, showed rescue effects even at a lower concentration than PLP, presenting a possible new therapeutic treatment for PNPO-deficiency NEE. Finally, GABA, a neurotransmitter whose biosynthesis depends on a PLP-dependent enzyme, showed some positive rescue effect. These results suggest zebrafish to be a promising PNPO-deficiency model for studying PLP homeostasis and drug therapy in vivo.

Diabetes mellitus is recognized as a major predisposing factor for Moraxella keratitis. However, how diabetes mellitus contributes to Moraxella keratitis remains unclear. In this study, we examined Moraxella keratitis; based on the findings, we investigated the impact of advanced glycation end products (AGEs) deposition in the cornea of individuals with diabetic mellitus on the adhesion of Moraxella isolates to the cornea. A retrospective analysis of 27 culture-proven cases of Moraxella keratitis at Ehime University Hospital (March 2006 to February 2022) was performed. Moraxella isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the patients, 30.4% had diabetes mellitus and 22.2% had the predominant ocular condition of using steroid eye drops. The species identified were Moraxella nonliquefaciens in 59.3% and Moraxella lacunata in 40.7% of patients. To investigate the underlying mechanisms, we assessed the effects of M. nonliquefaciens adherence to simian virus 40-immortalized human corneal epithelial cells (HCECs) with or without AGEs. The results demonstrated the number of M. nonliquefaciens adhering to HCECs was significantly increased by adding AGEs compared with that in controls (p < 0.01). Furthermore, in the corneas of streptozotocin-induced diabetic C57BL/6 mice treated with or without pyridoxamine, an AGE inhibitor, the number of M. nonliquefaciens adhering to the corneas of diabetic mice was significantly reduced by pyridoxamine treatment (p < 0.05). In conclusion, the development of Moraxella keratitis may be significantly influenced by the deposition of AGEs on the corneal epithelium of patients with diabetes mellitus., (© 2024. The Author(s).)

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The impact of diabetes mellitus on the central nervous system is less widely studied than in the peripheral nervous system, but there is increasing evidence that it elevates the risk of developing cognitive deficits. The aim of this study was to characterize the impact of experimental diabetes on the proteome and metabolome of the hippocampus. We tested the hypothesis that the vitamin B6 isoform pyridoxamine is protective against functional and molecular changes in diabetes. We tested recognition memory using the novel object recognition (NOR) test in streptozotocin (STZ)-induced diabetic, age-matched control, and pyridoxamine- or insulin-treated diabetic male Wistar rats. Comprehensive untargeted metabolomic and proteomic analyses, using gas chromatography-mass spectrometry and iTRAQ-enabled protein quantitation respectively, were utilized to characterize the molecular changes in the hippocampus in diabetes. We demonstrated diabetes-specific, long-term (but not short-term) recognition memory impairment and that this deficit was prevented by insulin or pyridoxamine treatment. Metabolomic analysis showed diabetes-associated changes in 13/82 identified metabolites including polyol pathway intermediates glucose (9.2-fold), fructose (4.9-fold) and sorbitol (5.2-fold). We identified and quantified 4807 hippocampal proteins; 806 were significantly altered in diabetes. Pathway analysis revealed significant alterations in cytoskeletal components associated with synaptic plasticity, glutamatergic signaling, oxidative stress, DNA damage and FXR/RXR activation pathways in the diabetic rat hippocampus. Our data indicate a protective effect of pyridoxamine against diabetes-induced cognitive deficits, and our comprehensive 'omics datasets provide insight into the pathogenesis of cognitive dysfunction enabling development of further mechanistic and therapeutic studies. • Pyridoxamine prevented long-term recognition memory deficits in diabetic rats. • Hippocampal protein changes are revealed by comprehensive untargeted proteomics. • Hippocampal metabolomic analysis showed increased polyol pathway intermediates. • Pyridoxamine altered synaptic plasticity-associated proteins in diabetic rats. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction. Methodology: In Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1β). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression. Results: Wistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1β were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFD-induced MetS rats in comparison to CTLs. Conclusions: Our findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage. [ABSTRACT FROM AUTHOR]

Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knockout and vitamin B6-deficient mice (KO/VB6 (-) mice), which are susceptible to methylglyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modified protein and the carbonyl stress status in the brain. A comparison between Wild/VB6(+) mice and KO/VB6(−) mice for accumulated carbonyl proteins levels, with several advanced glycation end products (AGEs) in the brain, revealed that carbonyl protein levels with the Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl) ornithine (MG-H1) moiety were significantly increased in the hippocampus, prefrontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrometry analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-adrenergic receptor kinase 1, and T-complex protein in the hippocampus region of KO/VB6(−) mice, but not in Wild/VB6(+) mice. In particular, MG-H1 modification of mitochondrial creatine kinase was quite notable. These results suggest that further studies focusing on MG-H1-modified and accumulated proteins in the hippocampus may reveal the onset mechanism of CS-SCZ induced by MGO-induced oxidative damages.

Diabetic complications present a serious health problem. Functional damage to proteins due to post-translational modifications by glycoxidation reactions is a known factor contributing to pathology. Extracellular proteins are especially vulnerable to diabetic damage because robust antioxidant defenses are lacking outside the cell. We investigated glucose-induced inactivation of peroxidasin (PXDN), a heme protein catalyzing sulfilimine crosslinking of collagen IV that reinforce the basement membranes (BM). Experiments using physiological diabetic glucose levels were carried out to exclude several potential mechanisms of PXDN inactivation i.e., direct adduction of glucose, reactive carbonyl damage, steric hindrance, and osmotic stress. Further experiments established that PXDN activity was inhibited via heme degradation by reactive oxygen species. Activity of another extracellular heme protein, myeloperoxidase, was unaffected by glucose because its heme was resistant to glucose-induced oxidative degradation. Our findings point to specific mechanisms which may compromise BM structure and stability in diabetes and suggest potential modes of protection. • Peroxidasin (PXDN) catalyzes crosslinking of collagen IV, thus contributing to extracellular matrix (ECM) stability. • PXDN is rapidly inactivated in the presence of diabetic levels of glucose. • PXDN inactivation is due to degradation of the heme by hydroxyl radical derived from oxidation of glucose. • Our findings point to specific mechanisms which may affect ECM functionality in diabetes. [ABSTRACT FROM AUTHOR]

The thermodynamic stability of 11 complexes of Cu(II) and 26 complexes of Fe(III) is studied, comprising the ligands pyridoxamine (PM), ascorbic acid (ASC), and a model Amadori compound (AMD). In addition, the secondary antioxidant activity of PM is analyzed when chelating both Cu(II) and Fe(III), relative to the rate constant of the first step of the Haber-Weiss cycle, in the presence of the superoxide radical anion (O2•−) or ascorbate (ASC−). Calculations are performed at the M05(SMD)/6-311+G(d,p) level of theory. The aqueous environment is modeled by making use of the SMD solvation method in all calculations. This level of theory accurately reproduces the experimental data available. When put in perspective with the stability of various complexes of aminoguanidine (AG) (which we have previously studied), the following stability trends can be found for the Cu(II) and Fe(III) complexes, respectively: ASC < AG < AMD < PM and AG < ASC < AMD < PM. The most stable complex of Cu(II) with PM (with two bidentate ligands) presents a ΔGf0 value of −35.8 kcal/mol, whereas the Fe(III) complex with the highest stability (with three bidentate ligands) possesses a ΔGf0 of −58.9 kcal/mol. These complexes can significantly reduce the rate constant of the first step of the Haber-Weiss cycle with both O2•− and ASC−. In the case of the copper-containing reaction, the rates are reduced up to 9.70 × 103 and 4.09 × 1013 times, respectively. With iron, the rates become 1.78 × 103 and 4.45 × 1015 times smaller, respectively. Thus, PM presents significant secondary antioxidant activity since it is able to inhibit the production of ·OH radicals. This work concludes a series of studies on secondary antioxidant activity and allows potentially new glycation inhibitors to be investigated and compared relative to both PM and AG.

Pyridoxamine (PM) is one of the natural vitamins B6 (VB6) and functions as an endogenous inhibitor for the formation of AGEs (advanced glycation end products). The AGEs are implicated in aging, diabetes, and various neuropsychiatric disease, including schizophrenia, Alzheimer's disease, and Parkinson's disease. However, it is unclear whether the absence of PM per se accumulates AGEs in vivo and causes behavioral dysfunctions. To address these points, we raised PM-deficient fruit flies, Drosophila melanogaster, with the sterilized defined medium. Flies reared in a PM-deficient medium accumulated AGEs and reduced lifespan, impaired gustatory response, sleep, courtship behavior, and olfactory learning. These results suggest that PM suppresses AGE accumulation in vivo and is required for regulating innate and empirical behaviors.

Naturally occurring forms of vitamin B6 include six interconvertible water-soluble compounds: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their respective monophosphorylated derivatives (PNP, PLP, and PMP). PLP is the catalytically active form which works as a cofactor in approximately 200 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. Most of vitamers can counteract the formation of reactive oxygen species and the advanced glycation end-products (AGEs) which are toxic compounds that accumulate in diabetic patients due to prolonged hyperglycemia. Vitamin B6 levels have been inversely associate with diabetes, while vitamin B6 supplementation reduces diabetes onset and its vascular complications. The mechanisms at the basis of the relation between vitamin B6 and diabetes onset are still not completely clarified. In contrast more evidence indicates that vitamin B6 can protect from diabetes complications through its role as scavenger of AGEs. It has been demonstrated that in diabetes AGEs can destroy the functionality of macromolecules such as protein, lipids, and DNA, thus producing tissue damage that result in vascular diseases. AGEs can be in part also responsible for the increased cancer risk associated with diabetes. In this chapter the relationship between vitamin B6, diabetes and AGEs will be discussed by showing the acquired knowledge and questions that are still open., (Copyright © 2024. Published by Elsevier Inc.)

Pyridoxamine, which is a form of vitamin B 6 , is a promising candidate for a prophylactic and/or remedy for diabetic complications. Pyridoxamine is chemically synthesized by an oxidative method in manufacturing. However, pyridoxamine production by bioconversion, which is generally preferable for environmental and energetic aspects, has been little investigated. Therefore, I aimed to produce pyridoxamine from pyridoxine, which is a readily and economically available starting material, by bioconversion using a Rhodococcus expression system. I found in the bioconversion of pyridoxine to pyridoxal, approximately 450 mM pyridoxal was produced from 500 mM pyridoxine using recombinant Rhodococcus erythropolis expressing the pyridoxine 4-oxidase gene derived from Mesorhizobium loti. Next, in the bioconversion of pyridoxal to pyridoxamine using recombinant R. erythropolis expressing the pyridoxamine-pyruvate aminotransferase gene derived from M. loti , the bioconversion rate was approximately 80% under the same conditions as pyridoxal production. Finally, in the bioconversion of pyridoxine to pyridoxamine through pyridoxal using recombinant R. erythropolis coexpressing the genes for pyridoxine 4-oxidase and pyridoxamine-pyruvate aminotransferase, the bioconversion rate was approximately 75%. Based on these findings, pyridoxamine production by bioconversion using a Rhodococcus expression system may be of interest for future industrial applications. [ABSTRACT FROM AUTHOR]

Abstract Hyperglycaemia is considered to be a driving factor for advanced glycated end products (AGEs). Inhibiting the process of glycation play an important role in reducing the diabetes related complications. We have explored the glucose mediated glycation and antiglycation activity of pyridoxamine using human serum albumin (HSA). Protein was incubated with glucose for 28 days at physiological temperature to achieve glycation. Antiglycation activity was assessed by the estimation of carbonyl content, free lysine and AGE specific fluorescence. Molecular docking was used to study the interaction of pyridoxamine with HSA and to get a detailed understanding of binding sites and binding energy. Glycation was reduced by pyridoxamine to commendable levels which was evident by the quantification of free lysine and carbonyl content. Pyridoxamine treatment also prevented the loss in secondary structure induced by glycation. It has also emerged as the quencher of reactive oxygen species which lead to the protection of DNA from oxidative damage. Pyridoxamine was found to be located at subdomain IIA of HSA with binding energy of −5.6 kcal/mol. These results are high points in the antiglycation activity of pyridoxamine. Its antioxidant nature and antiglycation activity are proof of its potential in preventing disease progression in diabetes. [ABSTRACT FROM AUTHOR]