Effects of a Tricaprylin Emulsion on Anti-glomerular Basement Membrane Glomerulonephritis in Rats: In Vivo and in Silico Studies

Biol Pharm Bull. 2015;38(8):1175-84. doi: 10.1248/bpb.b15-00124.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / drug therapy*
  • Autoantibodies
  • Caprylates / pharmacology
  • Caprylates / therapeutic use*
  • Computer Simulation
  • Emulsions
  • Glomerular Basement Membrane*
  • Glomerulonephritis / drug therapy
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney Failure, Chronic / prevention & control
  • Male
  • Microarray Analysis
  • Rats, Inbred Strains
  • Transcriptome
  • Triglycerides / pharmacology
  • Triglycerides / therapeutic use*

Substances

  • Autoantibodies
  • Caprylates
  • Emulsions
  • Triglycerides
  • antiglomerular basement membrane antibody
  • tricaprylin