Intravenous Pyridorin (pyridoxamine) / NephroGenex - LARVOL DELTA

Pyridoxamine Attenuates Doxorubicin-Induced Cardiomyopathy without Affecting Its Antitumor Effect on Rat Mammary Tumor Cells. (PubMed, Cells) - "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."

Journal • Preclinical • Tumor cell • Breast Cancer • Cardiomyopathy • Cardiovascular • Oncology • Solid Tumor • CASP3

Pyridoxamine Limits Cardiac Dysfunction in a Rat Model of Doxorubicin-Induced Cardiotoxicity. (PubMed, Antioxidants (Basel)) - "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."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Inflammation • TGFB1

New copper(II) and oxidovanadium(IV) complexes with a vitamin B Schiff base: mechanism of action and synergy studies on 2D and 3D human osteosarcoma cell models. (PubMed, Dalton Trans) - "We report the synthesis, characterization and anticancer activity of a new Schiff base (HL) derived from the condensation of pyridoxamine with pyridoxal and its novel copper(II) and oxidovanadium(IV) complexes: [Cu(HL)Cl] (1), [Cu(LH)(phen)]Cl (2), [Cu(LH)(amphen)]Cl (3), [VO(HL)Cl] (4), and [VO(LH)(phen)]Cl (5), where phen is 1,10-phenanthroline and amphen is its 5-amino derivative...Complexes 2 and 3 are also more active than cisplatin (CDDP)...Finally, compound 2 reduces the cell viability of MG-63 spheroids showing an IC value 7-fold lower than that of CDDP (8.5 ± 0.4 μM vs. 65 ± 6 μM). The combination of 2 and sorafenib also showed synergism on spheroids, suggesting that the combination of these drugs improves the anticancer effect against bone cancer cells."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Mechanism of peroxidasin inactivation in hyperglycemia: Heme damage by reactive oxygen species. (PubMed, Biochem Biophys Res Commun) - "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."

Journal • Diabetes • Metabolic Disorders • MPO

Pyridoxamine Limits Mitochondria-Dependent Ferroptosis in a Rat Model of Doxorubicin-Induced Cardiotoxicity (AHA 2023) - "In conclusion, we show that PM limits DOX-induced mitochondria-dependent ferroptosis, and could be a promising cardioprotective strategy for cancer patients."

Preclinical • Cardiovascular • Oncology

Gut Dysbiosis and Altered Gut-Derived Metabolites in Patients with Active Lupus Nephritis (KIDNEY WEEK 2023) - "LN is associated with gut dysbiosis and altered metabolite abundance. Whether these changes are of pathogenic significance remains to be established."

Clinical • Dysbiosis • Acute Kidney Injury • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Metabolic rewiring revealed by cell-specific rate analyses from nontargeted exometabolomics during simultaneous consumption of glucose and lactic acid in a CHO fed-batch process (ACS-Fall 2023) - "The analyses from the two metrics reveal a distinctive rearrangement of rates from the following metabolic pathways: (i) high secretion rates of carnitines as part of the acyl-group removal, (ii) low secretion rates of succinate, related to the tricarboxylic acid cycle and the electron transport chain, (iii) low secretion rates of pyridoxamine-5-phosphate – a co-factor for amino acid catabolism, transaminations, and transsulfuration, and (iv) increases in the consumption rates of glutamate and glycine, both used to produce glutathione. The rewiring in rates observed upon feeding lactic acid is best explained by the activation of pathways supporting homeostasis of acyl-groups and antioxidant synthesis, which are required for continuous proper functioning of oxidative phosphorylation."

Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE mice. (PubMed, Biomed Pharmacother) - "This study suggests that MGO spikes damages the vasculature independently of plasma glucose levels. Pyridoxamine and potentially other approaches to reduce MGO may prevent excess cardiovascular risk in diabetes."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • APOE • S100A9

Metabolic rewiring revealed by cell-specific rate analyses from nontargeted exometabolomics during simultaneous consumption of glucose and lactic acid in a CHO fed-batch process. (PubMed, J Biotechnol) - "The analyses from the two metrics reveal a distinctive rearrangement of rates from the following metabolic pathways: (i) high secretion rates of carnitines as part of the acyl-group removal, (ii) low secretion rates of succinate, related to the tricarboxylic acid cycle and the electron-transport chain, (iii) low secretion rates of pyridoxamine-5-phosphate - a co-factor for amino acid catabolism, transaminations, and transsulfuration, and (iv) increases in the consumption rates of glutamate and glycine, both used to produce glutathione. The rewiring in rates observed upon feeding lactic acid is best explained by the activation of pathways supporting homeostasis of acyl-groups and antioxidant synthesis, which are required for continuous proper functioning of oxidative phosphorylation."

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Exploitation of a rod-shaped, acid-labile curcumin-loaded polymeric nanogel system in the treatment of systemic inflammation. (PubMed, Mater Sci Eng C Mater Biol Appl) - "The constituent polymers of the nanogels were prepared via the conjugation of vitamin B derivatives, including pyridoxal and pyridoxamine, onto poly(glutamate) with ester bonds...Consequently, curcumin-loaded, rod-shaped nanogels displayed exceptional anti-inflammatory activity both in vitro and in vivo, by efficiently inhibiting pro-inflammatory mediator secretion. These results demonstrate the feasibility of our acid-labile, rod-shaped nanogels for the treatment of systemic inflammation."

Journal • Immunology • Inflammation

A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases. (PubMed, Eur J Pharmacol) - "Moreover, histopathological and immunohistological studies supported the ability of pyridoxamine to reduce liver fibrosis. The findings of the present study provide evidence that pyridoxamine is a novel target for the treatment of liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Oncology • CCL2 • MMP2 • MMP9 • TGFB1 • TIMP1 • TNFA

[VIRTUAL] Pyridoxamine Protects Against Cardiotoxicity After Doxorubicin Chemotherapy (AHA 2021) - "In conclusion, our data show that DOX causes dilated cardiomyopathy with reduced ejection fraction, accompanied by cardiac fibrosis and myocarditis. As PM limits this adverse phenotype, it could be a novel cardioprotective strategy for DOX-treated cancer patients."

Cardiomyopathy • Cardiovascular • Fibrosis • Heart Failure • Immunology • Inflammation • Oncology • IL6 • TGFB1

Biochemical and structural insights into PLP fold type IV transaminase from Thermobaculum terrenum. (PubMed, Biochimie) - "...The structures of TaTT in complex with the cofactor pyridoxal 5'-phosphate covalently bound to enzyme and in complex with its reduced form, pyridoxamine 5'-phosphate, were determined at resolutions of 2.19 Å and 1.5 Å, and deposited in the Protein Data Bank as entries 6GKR and 6Q8E, respectively...This study has shown for the first time that high substrate specificity towards both various L-amino acids and (R)-primary amines can be implemented within one pyridoxal 5'-phosphate-dependent active site of fold-type IV. These results complement our knowledge of the catalytic diversity of transaminases and indicate the need for further biochemical and bioinformatic studies to understand the sequence-structure-function relationship in these enzymes."

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