Antioxidant; Nrf-2/HO-1; Microbial Metabolite; Endogenous Metabolite

In addition to reducing ROS levels, cytoplasmic Nrf2 expression, and whole-cell HO-1 expression, pyridoxine has anti-adrenaline properties[1].
Pyridoxine is a water- soluble pyridine derivative. The effect of pyridoxine in cell models of Alzheimer's disease (AD), and the potential mechanisms involved, are not fully understood. In this study, the anti-AD effects of pyridoxine were studied in an AD cell model using a combination of techniques viz MTT assay, western blotting and assays for reactive oxygen species (ROS). Assays were also carried out to determine the mechanism underlying the antioxidant effects of pyridoxine. The results obtained revealed that pyridoxine exerted a protective potential against AD, attenuated ROS levels, decreased the expressions of cytoplasmic Nrf2, and upregulated whole-cell HO-1 expression. These results suggest that the anti-AD effect of pyridoxine may be attributed to its anti-oxidant property elicited via stimulation of the Nrf2/HO-1 pathway [1].

Objective: Linezolid is often used to treat antibacterial-resistant infections. Linezolid can cause side effects. To date, the effectiveness of the simultaneous administration of pyridoxine and linezolid is unclear. Here we investigate the protective effect of pyridoxine on linezolid-induced hematological toxicity, hepatotoxicity, and oxidative stress in rats.
Material and methods: The 40 male pediatric Spraque-Dawley rats were separated into 4 groups: control, linezolid, pyridoxine, and linezolid-pyridoxine. A complete blood count, liver function test, and measurements of antioxidant enzyme activities for superoxide dismutase, glutathione peroxidase, catalase, and lipid peroxidation were performed in blood before treatment and 2 weeks after administration of the treatment.
Results: White blood cell and hemoglobin counts for the linezolid group decreased, and the alanine aminotransferase level in the linezolid group increased compared to their respective baseline values. Post-treatment white blood cell decreased in the linezolid and linezolid- pyridoxine groups compared to those in the control group (P < .001). Alanine aminotransferase levels increased in the linezolid and linezolid-pyridoxine groups compared to those in the control group (P < .001 and P < .05, respectively). The activity of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde levels increased in the linezolid group compared to the control group (P < .001, P < .05, P < .001, and P < .001, respectively). Linezolid plus pyridoxine treatment caused a significant decrease in malondialdehyde levels and superoxide dismutase, catalase, and glutathione peroxidase enzyme activities compared to the linezolid group (P < .001, P < .01, P < .001, and P < .01, respectively).
Conclusion: pyridoxine may be an effective adjuvant agent for the prevention of linezolid toxicity in rat models [2].

Forty male pediatric Spraque–Dawley rats (8 weeks old, weighing 200-250 g) were divided into 4 groups: control (C, n = 10), linezolid (L, n = 10), pyridoxine (P, n = 10), and linezolid plus pyridoxine (LP, n = 10). For 14 days, by gavage twice a day, 1 mL of saline solution was administered to the C group. In addition, 125 mg/kg/day of linezolid was administered to the L group;100 mg/kg/day of pyridoxine was administered to the P group, and 125 mg/kg/day of linezolid and 100 mg/kg/day of pyridoxine to the LP group.

Absorption, Distribution and Excretion
Except for malabsorption syndrome, B vitamins are readily absorbed from the gastrointestinal tract. Pyridoxine is primarily absorbed in the jejunum. Peak plasma concentration (Cmax) of pyridoxine is reached within 5.5 hours. The major metabolite of pyridoxine, 4-pyridoxic acid, is inactive and excreted in the urine. The major active metabolite of pyridoxine, 5'-pyridoxal phosphate, is released into the bloodstream (accounting for at least 60% of circulating vitamin B6) and is highly bound to proteins, primarily albumin. Metabolism/Metabolites Pyridoxine is a prodrug, primarily metabolized in the liver. The metabolic pathway of pyridoxine is complex, involving the formation of primary and secondary metabolites and their interconversion with pyridoxine. The major metabolite of pyridoxine is 4-pyridoxic acid. Hepatic metabolism. Half-life: 15-20 days Biological half-life The total amount of pyridoxine in the adult body is 16 to 25 mg. Its half-life is approximately 15 to 20 days.

Toxicity Summary
Vitamin B6 is a collective term for three related compounds: pyridoxine (PN), pyridoxal (PL), and pyridoxamine (PM), as well as their phosphorylated derivatives: pyridoxine phosphate (PNP), pyridoxal phosphate (PLP), and pyridoxamine phosphate (PMP). While technically all six compounds should be called vitamin B6, the term "vitamin B6" is often used interchangeably with one of these compounds—pyridoxine. Vitamin B6 exists primarily in its biologically active coenzyme form—pyridoxal phosphate—and participates in a variety of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemoglobin, sphingomyelin, and other sphingolipids, and the synthesis of neurotransmitters such as serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid (GABA). Toxicity Data
LD50: 4 g/kg (oral, rat)

[1]. Pyridoxine exerts antioxidant effects in cell model of Alzheimer's disease via the Nrf-2/HO-1 pathway. Cell Mol Biol (Noisy-le-grand). 2018 Jul 30;64(10):119-124.

[2]. The Protective Effects of Pyridoxine on Linezolid-Induced Hematological Toxicity, Hepatotoxicity, and Oxidative Stress in Rats. Turk Arch Pediatr. 2023 May;58(3):298-301.

Pharmacodynamics
Vitamin B6 (pyridoxine) is a water-soluble vitamin used to prevent and treat vitamin B6 deficiency and peripheral neuropathy in patients taking isoniazid (isonicotinic acid hydrazide, INH). Studies have found that vitamin B6 can lower systolic and diastolic blood pressure in a small subset of patients with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed that pyridoxine hydrochloride can inhibit ADP- or adrenaline-induced platelet aggregation and lower total cholesterol levels while increasing high-density lipoprotein cholesterol (HDL-C) levels; this study also involved a small subset of subjects. Research has found that vitamin B6, in the form of pyridoxal phosphate, can protect cultured vascular endothelial cells from damage by activated platelets. Endothelial injury and dysfunction are key initiating events in the pathogenesis of atherosclerosis. Human studies have shown that vitamin B6 deficiency affects cellular and humoral immune responses of the immune system. Vitamin B6 deficiency can lead to altered immune activity, including abnormal lymphocyte differentiation and maturation, weakened delayed-type hypersensitivity (DTH), impaired antibody production, reduced lymphocyte proliferation, and decreased interleukin (IL)-2 production. We observed significantly increased antioxidant enzyme activity and malondialdehyde (MDA) levels in the erythrocytes of rats treated with linezolid. Previous studies have shown that antioxidant enzyme activity typically decreases after oxidative damage. However, in this study, both MDA levels and antioxidant enzyme activity increased after linezolid administration. This indicates that the antioxidant system was activated to scavenge free radicals generated by linezolid. Despite erythrocyte membrane damage, hemoglobin levels did not increase due to the absence of hemolysis. On the other hand, antioxidant enzyme and MDA levels did not increase in the L and LP groups. These changes induced by pyridoxine have been shown to reduce free radicals generated by linezolid and/or pyridoxine itself. It is recommended that pyridoxine be added to the treatment of Gram-positive bacterial infections to reduce the side effects of linezolid, thereby improving efficacy and preventing complications. Because linezolid's hematologic toxicity limits its application against multidrug-resistant Gram-positive pathogens, we believe this study will provide guidance for future research. [2]

C8H11NO3

169.1778

205.05

C, 46.73; H, 5.88; Cl, 17.24; N, 6.81; O, 23.34

58-56-0

65-23-6; 58-56-0 (hydrochloride); 27280-85-9 (oxoglurate);

1054

White to off-white solid powder

491.9ºC at 760 mmHg

214-215 °C(lit.)

251.3ºC

0.882

3

4

2

12

142

0

ZUFQODAHGAHPFQ-UHFFFAOYSA-N

InChI=1S/C8H11NO3.ClH/c1-5-8(12)7(4-11)6(3-10)2-9-5;/h2,10-12H,3-4H2,1H3;1H

3-Hydroxy-4,5-dihydroxymethyl-2-methylpyridine hydrochloride

Pyridoxine hydrochloride; PYRIDOXINE HYDROCHLORIDE; 58-56-0; Pyridoxine HCl; Pyridoxol hydrochloride; Vitamin B6 hydrochloride; Hexa-Betalin; Aderoxine; Alestrol; pyridoxol. vitamin B6.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 50 mg/mL (~243.14 mM)
DMSO : ≥ 50 mg/mL (~243.14 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (486.29 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)