ergosta-4-6-8(14)-22-tetraen-3-one and Kidney-Failure--Chronic

Ergosta-4,6,8(14),22-tetraen-3-one (ergone), isolated from the medicinal fungus Polyporus umbellatus, has been proven to prevent the progression of renal injury and the subsequent renal fibrosis. Ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) (MS(E)) data collection technique was employed to investigate metabonomic characters of chronic renal failure (CRF) induced adenine and the protective effects of ergosta-4,6,8(14),22-tetraen-3-one (ergone). Coupled with blood biochemistry and kidney histopathology results, the significant difference in metabolic profiling between adenine-induced CRF group and ergone-treated CRF group by using pattern recognition analysis indicated that changes in global faecal metabolites were occurred. Seven endogenous metabolites were identified by using metabonomic method combined with multivariate data analysis, the accurate mass, isotopic pattern, MS(E) fragments information and MassLynx i-FIT algorithm. These biochemical changes in faecal metabolites are related to the perturbations of bile acid metabolism and phospholipid metabolism, which may be helpful to further understand the CRF and therapeutic mechanisms of ergone. This research proved that MS(E) can simultaneous acquire precursor ion information and fragment ion data at high and low collision energy in one analytical run, which facilitated the fast structural characterization of metabolites.

Topics: Adenine; Animals; Cholestenones; Chromatography, High Pressure Liquid; Discriminant Analysis; Feces; Histocytochemistry; Kidney Failure, Chronic; Mass Spectrometry; Metabolomics; Rats

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.

Topics: Adenine; Animals; Aspartic Acid; Cholestenones; Chromatography, High Pressure Liquid; Creatinine; Dopamine; Kidney; Kidney Failure, Chronic; Lipid Metabolism; Lysophosphatidylcholines; Male; Metabolomics; Phenylalanine; Principal Component Analysis; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization