Badun Gennady A, Chernysheva Maria G, Zhernov Yury V, Poroshina Alina S, Smirnov Valery V, Pigarev Sergey E, Mikhnevich Tatiana A, Volkov Dmitry S, Perminova Irina V, Fedoros Elena I
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.
Department of General Hygiene, F. Erismann Institute of Public Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia.
Biomedicines. 2021 Nov 29;9(12):1787. doi: 10.3390/biomedicines9121787.
Natural products (e.g., polyphenols) have been used as biologically active compounds for centuries. Still, the mechanisms of biological activity of these multicomponent systems are poorly understood due to a lack of appropriate experimental techniques. The method of tritium thermal bombardment allows for non-selective labeling and tracking of all components of complex natural systems. In this study, we applied it to label two well-characterized polyphenolic compounds, peat fulvic acid (FA-Vi18) and oxidized lignin derivative (BP-Cx-1), of predominantly hydrophilic and hydrophobic character, respectively. The identity of the labeled samples was confirmed using size exclusion chromatography. Using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS), key differences in the molecular composition of BP-Cx-1 and FA-Vi18 were revealed. The labeled samples ([H]-FA-Vi18 (10 mg/kg) and [H]-BP-Cx-1 (100 mg/kg)) were administered to female BALB/c mice intravenously (i.v.) and orally. The label distribution was assessed in blood, liver, kidneys, brain, spleen, thymus, ovaries, and heart using liquid scintillation counting. Tritium label was found in all organs studied at different concentrations. For the fulvic acid sample, the largest accumulation was observed in the kidney (C 28.5 mg/kg and 5.6 mg/kg, respectively) for both routes. The organs of preferential accumulation of the lignin derivative were the liver (C accounted for 396.7 and 16.13 mg/kg for i.v. and p.o. routes, respectively) and kidney (C accounted for 343.3 and 17.73 mg/kg for i.v. and p.o. routes, respectively). Our results demonstrate that using the tritium labeling technique enabled successful pharmacokinetic studies on polyphenolic drugs with very different molecular compositions. It proved to be efficient for tissue distribution studies. It was also shown that the dosage of the polyphenolic drug might be lower than 10 mg/kg due to the sensitivity of the H detection technique.
几个世纪以来，天然产物（如多酚）一直被用作生物活性化合物。然而，由于缺乏合适的实验技术，这些多组分系统的生物活性机制仍知之甚少。氚热轰击法可以对复杂天然系统的所有成分进行非选择性标记和追踪。在本研究中，我们将其应用于标记两种特性明确的多酚化合物，分别是主要具有亲水性的泥炭富里酸（FA-Vi18）和主要具有疏水性的氧化木质素衍生物（BP-Cx-1）。使用尺寸排阻色谱法确认了标记样品的身份。利用超高分辨率傅里叶变换离子回旋共振质谱（FT ICR MS），揭示了BP-Cx-1和FA-Vi18分子组成的关键差异。将标记样品（[H]-FA-Vi18（10 mg/kg）和[H]-BP-Cx-1（100 mg/kg））静脉内（i.v.）和口服给予雌性BALB/c小鼠。使用液体闪烁计数法评估血液、肝脏、肾脏、大脑、脾脏、胸腺、卵巢和心脏中的标记分布。在所有研究的器官中都发现了不同浓度的氚标记。对于富里酸样品，两种给药途径在肾脏中观察到的积累量最大（分别为C 28.5 mg/kg和5.6 mg/kg）。木质素衍生物优先积累的器官是肝脏（静脉内和口服途径的C分别为396.7和16.13 mg/kg）和肾脏（静脉内和口服途径的C分别为343.3和17.73 mg/kg）。我们的结果表明，使用氚标记技术能够成功地对分子组成差异很大的多酚类药物进行药代动力学研究。它被证明对组织分布研究是有效的。还表明，由于H检测技术的敏感性，多酚类药物的剂量可能低于10 mg/kg。
