Liu Mingxing, Dong Jing, Yang Yajiang, Yang Xiangliang, Xu Huibi
Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074, China.
J Nanosci Nanotechnol. 2008 Jul;8(7):3493-9. doi: 10.1166/jnn.2008.136.
The aim of this study is to investigate the effect of poly(D, L-lactic acid) (PLA) nanoparticles as triptolide carrier on abating renal toxicity for Sprague Dawley rats after oral administration. Triptolide has severe toxicities on digestive, urogenital and blood circulatory system. High-resolution 600-MHz 1H-nuclear magnetic resonance (1H-NMR)-based metabolic analysis was performed on urine samples obtained from five groups of Sprague Dawley rats administrated with free triptolide and triptolide-loaded PLA nanoparticles at day 5, 10 and 15. The relative concentrations of biomarkers for renal lesion caused by triptolide were determined by 1H-NMR. The disorder of metabolism was characterized by the exceptional changes of the relative concentrations of succinate, 2-oxoglutarate and citrate. Similarly, the renal lesion was characterized by an increase of the relative concentrations of trimethylamine N-oxide and dimethylglycine, and a decrease of that of urea and allantoin. These results revealed that triptolide-loaded PLA nanoparticles might abate the renal toxicity of triptolide in comparison with identical doses of the free drug. The higher the dose (0.6 mg/kg), the more pronounced was this trend during long-term application. These results were further confirmed by histopathological changes. These results indicated that PLA nanoparticles provided a promising new formulation to abate the renal toxicity caused by triptolide.
本研究旨在探讨聚（D，L-乳酸）（PLA）纳米颗粒作为雷公藤内酯醇载体对口服给药后Sprague Dawley大鼠肾脏毒性的减轻作用。雷公藤内酯醇对消化、泌尿生殖和血液循环系统有严重毒性。在第5、10和15天，对五组分别给予游离雷公藤内酯醇和载雷公藤内酯醇PLA纳米颗粒的Sprague Dawley大鼠采集的尿液样本进行基于600-MHz高分辨率1H-核磁共振（1H-NMR）的代谢分析。通过1H-NMR测定由雷公藤内酯醇引起的肾损伤生物标志物的相对浓度。代谢紊乱表现为琥珀酸、2-氧代戊二酸和柠檬酸相对浓度的异常变化。同样，肾损伤表现为氧化三甲胺和二甲基甘氨酸相对浓度升高，尿素和尿囊素相对浓度降低。这些结果表明，与相同剂量的游离药物相比，载雷公藤内酯醇PLA纳米颗粒可能减轻雷公藤内酯醇的肾脏毒性。剂量越高（0.6 mg/kg），长期应用时这种趋势越明显。组织病理学变化进一步证实了这些结果。这些结果表明，PLA纳米颗粒为减轻雷公藤内酯醇引起的肾脏毒性提供了一种有前景的新制剂。
