Effect of ergosta-4,6,8(14),22-tetraen-3-one (ergone) on adenine-induced chronic renal failure rat: A serum metabonomic study based on ultra performance liquid chromatography/high-sensitivity mass spectrometry coupled with MassLynx i-FIT algorithm

• Published in: Clinica chimica acta Vol. 413; no. 19-20; pp. 1438 - 1445
• Main Authors: Zhao, Ying-Yong, Cheng, Xian-Long, Cui, Ji-Hong, Yan, Xing-Rong, Wei, Feng, Bai, Xu, Lin, Rui-Chao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 09.10.2012
• Subjects: Adenine - adverse effects; Adenine - blood; Animals; Aspartic Acid - blood; Cholestenones - administration & dosage; Chromatography, High Pressure Liquid; Chronic renal failure; Creatinine - blood; Dopamine - blood; Ergosta-4,6,8,22-tetraen-3-one; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - prevention & control; Lipid Metabolism; Lysophosphatidylcholines - blood; Male; MassLynx i-FIT algorithm; Metabolomics; Metabonomics; Phenylalanine - blood; Polyporus umbellatus; Principal Component Analysis; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; UPLC/HSMS; Polyporus umbellatus; Chronic renal failure; UPLC/HSMS; MassLynx i-FIT algorithm; Ergosta-4,6,8,22-tetraen-3-one; Metabonomics
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2012.06.005

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. A serum metabonomic method based on the UPLC Q-TOF/MS was undertaken to explore the excretion pattern of low molecular mass metabolites. 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. 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. ► Serum metabolic profiling of ergone therapeutic CRF rats was developed by UPLC–HSMS. ► The alterations were associated with amino acids and phospholipid metabolism. ► Metabonomics is helpful in understanding the therapeutic effect mechanism of CRF.