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An epoxyeicosatrienoic acid analog treated adriamycin‐induced proteinuria and renal fibrosis
Author(s) -
Khan Md Abdul Hye,
Goldspink Paul,
Imig John D,
Falck John R
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.998.11
Subject(s) - proteinuria , medicine , kidney disease , population , kidney , urology , urine , excretion , metabolite , endocrinology , pharmacology , environmental health
Chronic Kidney Disease (CKD) is a global health concern affecting 16% of the population and an estimated 33 million Americans. Persistent proteinuria and renal fibrosis are the two major contributors in CKD and its progression to end‐stage renal disease. Epoxyeicosatrienoic acid (EET), a CYP epoxygenase metabolite of arachidonic acid, and the EET analogs demonstrated diverse biological actions including renal protection. The aim of this study was to determine if EET‐A, an EET analog, could be used as a treatment for CKD using an adriamycin‐induced kidney injury model. Adriamycin (ADR; 10mg/kg i.v.) was administered to two groups (n=8/group) of male Balb/c mice (8–10 weeks old) whilst the control received saline (i.v.). Urine samples were collected 5 days after ADR injection and 24hr urinary protein excretion was determined. The ADR mice (15.0±4 mg/d) developed elevated proteinuria 5 days after ADR injection compared to control (2.4±0.4 mg/d). After confirming proteinuria 5 days post ADR administration, the ADR mice were treated with vehicle or EET‐A (10mg/kg in drinking water) for two weeks. In ADR mice, EET‐A treatment was able to prevent further proteinuria (11±2 mg/d) compared to the vehicle (25±4 mg/d). EET‐A treatment also reduced renal fibrosis in ADR mice by lowering the collagen positive fibrotic area (1.0±0.1%) compared to vehicle (4.0±1.2%). Overall, the data demonstrated that EET‐A treated ADR‐induced proteinuria and renal fibrosis, and has potential for CKD treatment. Support or Funding Information Research Starter Grant to Md. AH Khan from PhRMA Foundation, USA