Effect of poly(D, L-lactic acid) nanoparticles as triptolide carrier on abating rats renal toxicity by NMR-based metabolic analysis.
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.
Liu
Mingxing
M
Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074, China.
Dong
Jing
J
Yang
Yajiang
Y
Yang
Xiangliang
X
Xu
Huibi
H
D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage* / Q000633:toxicity* / Q000652:urine; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000633:toxicity / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008744:Methylamines / Q000652:urine; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000633:toxicity* / Q000652:urine; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012521:Sarcosine / Q000031:analogs & derivatives / Q000652:urine; D013997:Time Factors
D004224:Diterpenes; D004337:Drug Carriers; D004852:Epoxy Compounds; D008744:Methylamines; D010616:Phenanthrenes; D011091:Polyesters; D011108:Polymers; C001899:triptolide; D019344:Lactic Acid; C033616:poly(lactide); C025138:dimethylglycine; C005855:trimethyloxamine; D012521:Sarcosine