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

通过降低 ROS 水平、下调细胞质 Nrf2 表达和上调全细胞 HO-1 表达，吡哆醇显示出其针对 AD 的保护潜力 [1]。 除了降低 ROS 水平、细胞质 Nrf2 表达和全细胞 HO-1 表达外，吡哆醇还具有抗肾上腺素特性 [1]。
吡哆醇是一种水溶性吡啶衍生物。吡哆醇在阿尔茨海默病（AD）细胞模型中的作用及其潜在机制尚不完全清楚。在这项研究中，使用MTT法、蛋白质印迹法和活性氧（ROS）测定法等技术，在AD细胞模型中研究了吡哆醇的抗AD作用。还进行了检测，以确定吡哆醇抗氧化作用的机制。所获得的结果表明，吡哆醇对AD具有保护作用，降低了ROS水平，降低了细胞质Nrf2的表达，上调了全细胞HO-1的表达。这些结果表明，吡哆醇的抗AD作用可能归因于其通过刺激Nrf2/HO-1途径引发的抗氧化特性[1]。

目的：利奈唑胺常用于治疗耐药性感染。利奈唑胺会引起副作用。迄今为止，同时给予pyridoxine/吡哆醇和利奈唑胺的有效性尚不清楚。在这里，我们研究了吡哆醇对利奈唑胺诱导的大鼠血液毒性、肝毒性和氧化应激的保护作用
材料和方法：将40只雄性幼年Spraque-Dawley大鼠分为4组：对照组、利奈唑胺组、吡哆醇组和利奈唑啉吡啶酮组。在治疗前和治疗后2周，在血液中进行全血细胞计数、肝功能测试以及超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶和脂质过氧化的抗氧化酶活性测量
结果：与各自的基线值相比，利奈唑胺组的白细胞和血红蛋白计数降低，丙氨酸氨基转移酶水平升高。与对照组相比，利奈唑啉和利奈唑胺-吡哆醇组治疗后白细胞减少（P<0.001）。与对照组相比，利奈唑啉和利奈唑胺-吡哆醇组的丙氨酸氨基转移酶水平升高（分别为P<0.001和P<0.05）。与对照组相比，利奈唑胺组的超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和丙二醛水平升高（分别为P<0.001、P<0.05、P<0.001和P<0.001）。与利奈唑胺组相比，利奈唑啉加吡哆醇治疗导致丙二醛水平和超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性显著降低（分别为P<0.001、P<0.01、P<0.001和P<0.01）
结论：pyridoxine/吡哆醇可能是预防大鼠利奈唑胺毒性的有效佐剂[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
The B vitamins are readily absorbed from the gastrointestinal tract, except in malabsorption syndromes. Pyridoxine is absorbed mainly in the jejunum. The Cmax of pyridoxine is achieved within 5.5 hours.
The major metabolite of pyridoxine, 4-pyridoxic acid, is inactive and is excreted in urine
Pyridoxine main active metabolite, pyridoxal 5’-phosphate, is released into the circulation (accounting for at least 60% of circulating vitamin B6) and is highly protein bound, primarily to albumin.

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Metabolism / Metabolites
Pyridoxine is a prodrug primarily metabolized in the liver. The metabolic scheme for pyridoxine is complex, with formation of primary and secondary metabolites along with interconversion back to pyridoxine. Pyridoxine's major metabolite is 4-pyridoxic acid.
Hepatic.
Half Life: 15-20 days

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Biological Half-Life
The total adult body pool consists of 16 to 25 mg of pyridoxine. Its half-life appears to be 15 to 20 days.

Toxicity Summary
Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

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Toxicity Data
LD50: 4 gm/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 in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.

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We observed a significant increase in antioxidant enzyme activity and MDA levels in erythrocytes for rats treated with linezolid. Previous studies have shown that antioxidant enzyme activities generally decrease after oxidative damage. However, in our study, MDA levels and antioxidant enzyme activities were increased after the administration of linezolid. This suggested that the antioxidant system was activated to remove free radicals from linezolid. Although membrane damage occurs in erythrocytes, the lack of adequate hemoglobin levels was attributed to the absence of hemolysis. On the other hand, both antioxidant enzymes and MDA levels were not elevated in L and LP groups. These changes induced by pyridoxine have been shown to decrease the free radical production due to linezolid and/or free radicals formed by the help of pyridoxine. The addition of pyridoxine to protect against the side effects of linezolid used in the treatment of gram-positive bacterial infections should be recommended to increase the effectiveness of treatment and prevent complications. Since the hematological toxic effects of linezolid limit its use against multidrug-resistance gram-positive pathogens, we believe that this study will be promising to guide future research. [2]

C8H11NO3

169.1778

169.073

C, 56.80; H, 6.55; N, 8.28; O, 28.37

65-23-6

Pyridoxine-d5;688302-31-0;Pyridoxine hydrochloride;58-56-0

1054

White to off-white solid powder

1.4±0.1 g/cm3

491.9±40.0 °C at 760 mmHg

159-162ºC

251.3±27.3 °C

0.0±1.3 mmHg at 25°C

1.621

-1.1

73.58

3

4

2

12

142

0

LXNHXLLTXMVWPM-UHFFFAOYSA-N

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

4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol

pyridoxine; 65-23-6; Pyridoxol; Pyridoxin; 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridine; Adermine; Gravidox; Hydoxin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~100 mg/mL (~591.09 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (12.29 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (12.29 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (12.29 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
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6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。