Integrated renal metabolomic and metallomic profiling revealed protective effect and metabolic mechanism of Gushudan on glucocorticoid-induced osteoporotic rat based on GC-MS and ICP-MS

Abstract

Based on the traditional Chinese medicine theory, kidney is considered to govern the bones and dominate the store of essence (‘jing’ in Chinese). Gushudan (GSD) is a traditional Chinese medicine prescription for the treatment osteoporosis in the clinic and is beneficial for improving kidney function and strengthening bone in vivo. This study aims to reveal the renal metabolic profiling of glucocorticoid-induced osteoporosis (GIOP) rats and the potential preventive effect of GSD based on an integrative metabolomic and metallomic approach. Gas chromatography-mass spectrometry (GC–MS) and inductively coupled plasma mass spectrometry (ICP-MS) were combined for the investigation of renal metabolomic and metallomic profiling. In the metabolomic analysis, 17 potential biomarkers were found to be related to GIOP, such as glucose, malate, γ-aminobutyric acid and arachidonic acid. And seven metallic elements, including Zn, Mn, Se, Fe, Mo, As and Ba, were identified in rat kidney tissue in the metallomic analysis. The major metabolic pathways included aerobic glycolysis, and neurotransmitter amino acids metabolism. It was worth mentioning that the levels of trace metal elements (Zn, Mn, Se, Fe, As and Ba) significantly reduced in the model group, while the contents of Zn, Mn, Se, Fe and As were elevated after administration of GSD. Finally, a correlation metabolic regulatory network and the metabolic pathways associated with trace metal elements were further investigated to illuminate the role of potential biomarkers and trace metal elements in GIOP rats. These variations of potential biomarkers and trace metal elements suggested the existence of kidney damage and metabolic disorder in GIOP rats, which indicated a close relationship between bone and kidney in vivo. Moreover, the integrated renal metabolomic and metallomic profiling could be as an effective supplementary measure to the plasma and urine metabolomic research, and it was helpful to further understand the holistic formation process of osetoporosis and the potential preventive effects of GSD on GIOP rats.