TY - JOUR
T1 - A pharmaco-metabonomic study on chronic kidney disease and therapeutic effect of Ergone by UPLC-QTOF/HDMS
AU - Zhao, Ying Yong
AU - Chen, Hua
AU - Tian, Ting
AU - Chen, Dan Qian
AU - Bai, Xu
AU - Wei, Feng
AU - Dzeja, Petras
N1 - Publisher Copyright:
© 2014 Zhao et al.
PY - 2014/12/23
Y1 - 2014/12/23
N2 - Chronic kidney disease (CKD) is an important public health problem. Ergone has been proved to prevent the progression of CKD. UPLC-QTOF/HDMS was employed for metabolic profiling of adenine-induced CKD and to investigate the nephroprotective effects of ergone. Pharmacology parameters including blood biochemistry, histopathological evaluation and Western blot analysis were performed concurrently. The UPLC-MS data were analyzed by partial least squares-discriminate analysis, correlation analysis, heatmap analysis and mapped to KEGG pathways. Blood and serum biochemistry were observed to be significantly different in the CKD group than in the control group. In conjunction with biochemistry, histopathology and protein expression results, identified metabolites indicated perturbations in fatty acid metabolism, purine metabolism and amino acid metabolism as changes associated with adenine-induced CKD and the interventions of ergone. Upregulated expression of TGF-b1, ED-1, CTGF, bFGF and collagen I was observed in the CKD group. However, downregulated expression of these proteins was observed after oral administration of ergone. These results suggest that expression changes in these proteins had implications for fatty acid metabolism, purine metabolism and amino acid metabolism in the development of CKD and that ergone treatment could delay the development of CKD by normalizing or blocking abnormal changes in biomarker metabolites and protein expression in the CKD group.
AB - Chronic kidney disease (CKD) is an important public health problem. Ergone has been proved to prevent the progression of CKD. UPLC-QTOF/HDMS was employed for metabolic profiling of adenine-induced CKD and to investigate the nephroprotective effects of ergone. Pharmacology parameters including blood biochemistry, histopathological evaluation and Western blot analysis were performed concurrently. The UPLC-MS data were analyzed by partial least squares-discriminate analysis, correlation analysis, heatmap analysis and mapped to KEGG pathways. Blood and serum biochemistry were observed to be significantly different in the CKD group than in the control group. In conjunction with biochemistry, histopathology and protein expression results, identified metabolites indicated perturbations in fatty acid metabolism, purine metabolism and amino acid metabolism as changes associated with adenine-induced CKD and the interventions of ergone. Upregulated expression of TGF-b1, ED-1, CTGF, bFGF and collagen I was observed in the CKD group. However, downregulated expression of these proteins was observed after oral administration of ergone. These results suggest that expression changes in these proteins had implications for fatty acid metabolism, purine metabolism and amino acid metabolism in the development of CKD and that ergone treatment could delay the development of CKD by normalizing or blocking abnormal changes in biomarker metabolites and protein expression in the CKD group.
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U2 - 10.1371/journal.pone.0115467
DO - 10.1371/journal.pone.0115467
M3 - Article
C2 - 25535749
AN - SCOPUS:84919798332
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 12
M1 - e115467
ER -