NAD⁺ deficiency has recently been linked with increased occurrences of congenital abnormalities and embryonic death in human and animal subjects. Early embryonic death is a major component of pregnancy loss in mares and very little is known regarding the requirement for NAD⁺ in horses. The aim of this study was to quantify NAD⁺ and its metabolites in the plasma and urine of mares after orally administering an acute dose of nicotinic acid and determine the absorption, metabolism and excretion of this essential precursor for NAD⁺ biosynthesis. Nicotinic acid (5 g per os) was administered to four mares via a dosing syringe. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6 and 22 h, and urine samples were collected at 0, 3, 6 and 22 h. The samples were processed and analysed by mass spectrometry. A general additive model was applied to all metabolite concentration values followed by a post-hoc multiple comparisons test. Nicotinic acid was rapidly absorbed into peripheral blood within 15 min of administration and the concentrations of nicotinic acid, nicotinamide (NAM), nicotinuric acid, nicotinic acid mononucleotide and nicotinic acid adenine dinucleotide (NaAD) increased significantly in plasma at 30 min. The concentrations of NAM, nicotinic acid riboside and NaAD increased significantly in urine at 3 h. The levels of NAM and NaAD remained significantly elevated in plasma at 22 h, sixfold and ninefold greater, respectively, than the basal levels at 0 h. While the extracellular levels of NAD⁺ in the samples remained undetected, the large, sustained elevation of NaAD levels in plasma indicates that the NAD⁺ levels were boosted within the cellular compartments. The results show that nicotinic acid supplementation increases the bioavailability of NAD⁺ precursors in mares, which is proposed to be beneficial during periods of peak NAD⁺ demand, such as during early embryo development.

中文翻译：

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以超生理剂量补充烟酸可增加母马 NAD+ 前体的生物利用度

NAD ⁺缺乏最近与人类和动物受试者中先天性异常和胚胎死亡的发生率增加有关。^{早期胚胎死亡是母马妊娠丢失的主要组成部分，而关于马对 NAD +}的需求知之甚少。本研究的目的是量化口服急性剂量烟酸后母马血浆和尿液中的NAD ^{+及其代谢物，并确定这种 NAD +必需前体的吸收、代谢和排泄}生物合成。通过给药注射器向四匹母马施用烟酸（每口 5 克）。0、0.25、0.5、1、2、4、6、22 h采集血样，0、3、6、22 h采集尿样。样品经过质谱处理和分析。对所有代谢物浓度值应用通用加法模型，然后进行事后多重比较测试。烟酸在给药后15分钟内迅速吸收到外周血中，30分钟血浆中烟酸、烟酰胺（NAM）、烟尿酸、烟酸单核苷酸和烟酸腺嘌呤二核苷酸（NaAD）的浓度显着增加。3 h时尿液中NAM、烟酸核苷和NaAD的浓度显着增加。血浆中 NAM 和 NaAD 的水平在 22 小时时仍然显着升高，分别是 0 小时时的基础水平的 6 倍和 9 倍。虽然 NAD 的细胞外水平^{样本中的+}仍未检测到，血浆中 NaAD 水平的大幅持续升高表明 NAD ⁺水平在细胞隔间内得到了提高。结果表明，补充烟酸可提高母马中 NAD ⁺前体的生物利用度，这在 NAD ⁺需求高峰期（例如早期胚胎发育期间）是有益的。