title: Effects of a Tricaprylin Emulsion on Anti-glomerular Basement Membrane Glomerulonephritis in Rats: In Vivo and in Silico Studies.
abstract: Glomerulonephritis (GN) is a set of pathological conditions that result in the destruction of glomeruli and loss of renal function, commonly leading to the development of end-stage renal disease. Current pharmacotherapy is limited to immunosuppressive therapy. In the present study, we found a novel antinephritic effect of a tricaprylin emulsion in the anti-glomerular basement membrane (anti-GBM) GN rat model. We evaluated the treatment in vivo by comparing administration of the emulsion with administration of a casein kinase II (CK2) inhibitor in this rat model, and performed a gene ontology-based microarray analysis to reveal in silico the detailed mechanism of action. Our results showed that administration of the tricaprylin emulsion, or even tricaprylin alone, significantly ameliorated the anti-GBM antibody-induced renal dysfunction in these rats. We believe that tricaprylin is the key active antinephritic component of the emulsion and might be a promising drug for the effective treatment of nephritis. Moreover, with respect to microarray analysis, we developed a generally applicable and rapid method to compare gene expression profile data for multiple models of nephritis and clinical samples from a public domain microarray database.
authors.affiliation: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.forename: Misato
authors.initials: M
authors.lastname: Yasue
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takei
authors.forename: Hayato
authors.initials: H
authors.lastname: Sanefuji
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy*; D001323:Autoantibodies; D002210:Caprylates / Q000494:pharmacology / Q000627:therapeutic use*; D003198:Computer Simulation; D004655:Emulsions; D050533:Glomerular Basement Membrane; D005921:Glomerulonephritis / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008297:Male; D046228:Microarray Analysis; D011919:Rats, Inbred Strains; D059467:Transcriptome; D014280:Triglycerides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001323:Autoantibodies; D002210:Caprylates; D004655:Emulsions; D014280:Triglycerides; C051951:antiglomerular basement membrane antibody; C003637:tricaprylin