Metabolomic evaluation of Euphorbia pekinensis induced nephrotoxicity in rats

Context:Euphorbia pekinensis Rupr. (Euphorbiaceae) has long been used in the Orient, while its clinical use was limited due to its nephrotoxic effect. Objective: The possible mechanism of nephrotoxicity of Euphorbia pekinensis (EPR) and its related constituents were investigated. Materials and methods: Petroleum ether (PE), acetic ether (AE) and n-butanol (BUT) extracted sections of EPR were separately given to Wistar rats by gavage at the dose of 3 g/kg/day for 10 weeks to determine the nephrotoxic section of EPR. Then, renal metabolic profiling of EPR after oral administration of nephrotoxic section was investigated and its related constituents were identified by LC/Q-TOF-MS method. Results: The average values of creatinine (CREA) in PE, AE, BUT and control groups were 76.54 ± 9.52, 54.12 ± 10.34, 51.33 ± 5.19 and 48.23 ± 6.67 μmol/L. The average values of blood urea nitrogen (BUN) in PE, AE, BUT and control groups were 15.25 ± 3.37, 8.32 ± 0.89, 9.22 ± 1.78 and 8.47 ± 1.33 mmol/L, respectively. Only kidney section of rats in PE group showed that glomeruli had cellular or fibrocellular crescents. Renal metabolic profiling showed disturbed metabolic pathways of purine, amino acid, phospholipids and sphingolipids in EPR nephrotoxicity. A total of 25 compounds [(–)-(1S)-15-hydroxy-18-carboxycembrene is a new compound] in PE section and 10 compounds in rat serum after administration of PE section were identified. Conclusions: This is the first time that the toxic compounds of PER and action mechanism of EPR nephrotoxicity were explored to provide a new reference for studying the toxic components of Traditional Chinese Medicine (TCM).