2. Academic Validation
  3. 8,9-Epoxyeicosatrienoic acid protects the glomerular filtration barrier

8,9-Epoxyeicosatrienoic acid protects the glomerular filtration barrier

  • Prostaglandins Other Lipid Mediat. 2009 Jun;89(1-2):43-51. doi: 10.1016/j.prostaglandins.2009.04.004.
Mukut Sharma 1,  Ellen T McCarthy,  D Sudarshan Reddy,  Paresh K Patel,  Virginia J Savin,  Meetha Medhora,  John R Falck
Affiliations

Affiliation

  • 1 Division of Nephrology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. msharma@mcw.edu
PMID: 19480064 DOI: 10.1016/j.prostaglandins.2009.04.004
Abstract

Glomerular dysfunction and proteinuria characterize focal segmental glomerulosclerosis (FSGS) associated with chronic kidney disease. FSGS is resistant to treatment and a circulating permeability factor (FSPF) frequently causes post-renal transplantation recurrence. In order to explore the role of 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs), we determined their effect on FSPF-induced increase in glomerular albumin permeability (P alb) using an in vitro assay. Exogenous 8,9-EET (1-1000 nM) dose-dependently prevented the FSPF-induced increase in P alb. The Other three EET regioisomers, 8,9-EET metabolite, 8,9-dihydroxyeicosatrienoic acid and unrelated 11,14-eicosadienoic acid (100 nM each) were not effective suggesting specificity of the observed glomerular protection by 8,9-EET. Synthetic analogs of 8,9-EET containing one double bond antagonized the effect of 8,9-EET on the FSPF-induced increase in P alb. Analogs containing two double bonds did not antagonize the effect of 8,9-EET and significantly blocked the FSPF-induced increase in P alb. These novel findings suggest a unique protective role for 8,9-EET in the glomerulus. Stable analogs of 8,9-EET may be valuable in developing effective management/treatment of glomerular dysfunction.

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