BACKGROUND: Ergosta-4,6,8(14),22-tetraen-3-one (ergone) has been proven to prevent the progression of renal injury and the subsequent renal fibrosis. We investigated the therapeutic effects and mechanism of ergone on a chronic renal failure model of rats induced by adenine. METHODS: A serum metabonomic method based on the UPLC Q-TOF/MS was undertaken to explore the excretion pattern of low molecular mass metabolites. RESULTS: Coupled with blood biochemistry and kidney histopathology results, the significant difference in metabolic profiling between adenine-induced chronic renal failure group and the ergone treated group by using pattern recognition analysis indicated that changes in global serum metabolites occurred. Some significantly changed metabolites like lysophosphatidylcholines, adenine, dopamine, creatinine, aspartic acid and phenylalanine have been found and identified. These biochemical changes in serum metabolites are related to the perturbations of amino acid metabolism and lecithin metabolism, which may be helpful to further understand the chronic renal failure and therapeutic mechanisms of ergone. CONCLUSION: The work shows that the metabonomic method is a valuable tool for studying the essence of chronic kidney disease and therapeutic effect mechanism of preclinical or clinical drug.
BACKGROUND:Ergosta-4,6,8(14),22-tetraen-3-one (ergone) has been proven to prevent the progression of renal injury and the subsequent renal fibrosis. We investigated the therapeutic effects and mechanism of ergone on a chronic renal failure model of rats induced by adenine. METHODS: A serum metabonomic method based on the UPLC Q-TOF/MS was undertaken to explore the excretion pattern of low molecular mass metabolites. RESULTS: Coupled with blood biochemistry and kidney histopathology results, the significant difference in metabolic profiling between adenine-induced chronic renal failure group and the ergone treated group by using pattern recognition analysis indicated that changes in global serum metabolites occurred. Some significantly changed metabolites like lysophosphatidylcholines, adenine, dopamine, creatinine, aspartic acid and phenylalanine have been found and identified. These biochemical changes in serum metabolites are related to the perturbations of amino acid metabolism and lecithin metabolism, which may be helpful to further understand the chronic renal failure and therapeutic mechanisms of ergone. CONCLUSION: The work shows that the metabonomic method is a valuable tool for studying the essence of chronic kidney disease and therapeutic effect mechanism of preclinical or clinical drug.
Authors: Ming Wang; Dan-Qian Chen; Lin Chen; Gang Cao; Hui Zhao; Dan Liu; Nosratola D Vaziri; Yan Guo; Ying-Yong Zhao Journal: Br J Pharmacol Date: 2018-05-22 Impact factor: 8.739