Effect of Poly(D, L-lactic acid) Nanoparticles as Triptolide Carrier on Abating Rats Renal Toxicity by NMR-Based Metabolic Analysis

Abstract

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.