Cited by 59Inflammatory mediators and NSAID effectsChronic Kidney Disease and DiabetesPeroxisome Proliferator-Activated Receptors

Fenofibrate Treatment of Diabetic Rats Reduces Nitrosative Stress, Renal Cyclooxygenase-2 Expression, and Enhanced Renal Prostaglandin Release

Chen, Yu-Jung, Quilley, John·2008·The Journal of Pharmacology and Experimental Therapeutics

Abstract

Renal cyclooxygenase (COX)-2 expression is increased in the diabetic rat and has been linked to increased glomerular filtration rate (GFR) and renal injury. Our studies indicate that oxidative stress in the form of peroxynitrite (ONOO) may be the stimulus for induction of COX-2. In this study, we addressed the effects of a peroxisome proliferator-activated receptor alpha agonist on renal COX-2 expression as fibrates exert renal protective effects. Forty-eight hours after the induction of diabetes with streptozotocin in male Wistar rats, fenofibrate treatment (100 mg/kg/day) was started, and the effects were compared with untreated diabetic rats and treated and untreated age-matched control rats (n = 5 per group). After 12 to 14 weeks of treatment, the right kidney was perfused to determine prostaglandin release in response to arachidonic acid (AA), and the left kidney was used to examine the expression of COX-2 and nitrotyrosine, an index of ONOO formation. Release of prostaglandin (PG) E(2) in response to AA was enhanced in the diabetic rat kidney compared with control (4.8 +/- 0.7 versus 1.9 +/- 0.7 ng/min) and reduced by fenofibrate to 0.6 +/- 0.2 ng/min. A similar pattern was obtained for AA-stimulated release of 6-ketoPGF(1alpha). The effects of fenofibrate were associated with reduced renal expression of COX-2 and nitrotyrosine in diabetic rats. We used creatinine clearance as an index of GFR, which was increased in the diabetic rat, 3.09 +/- 0.4 versus 1.15 +/- 0.1 ml/…

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Crossref · 10.1124/jpet.107.129197

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  • The investigators of the experimental study concluded that fenofibrate may attenuate diabetes-induced hyperfiltration by preventing the upregulation of renal cyclooxygenase-2 expression that accompanies diabetes.

    “The investigators concluded that fenofibrate may attenuate diabetes-induced hyperfiltration by preventing the upregulation of renal cyclooxygenase-2 expression that accompanies diabetes.26”

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Authors
Chen, Y.-J., & Quilley, J.
Affiliations
New York Medical College (US)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2008-02
Volume
324
Issue
2
Pages
658-663
ISSN
0022-3565 (ISSN-L)
OpenAlex
W2075372190
Cited by
59
References
37
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 6
FWCI
1.99
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL069061)
Topics
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
fenofibrate, diabetic nephropathy, cyclooxygenase-2, nitrosative stress, peroxynitrite, nitrotyrosine, arachidonic acid, glomerular filtration rate, PPARα, fibrates, streptozotocin-induced diabetes, kidney injury
MeSH terms
Animals, Diabetes Mellitus, Experimental, Kidney, Male, Fenofibrate, Prostaglandins, Tyrosine, Gene Expression Regulation, Enzymologic, Rats, Wistar, Rats, Cyclooxygenase 2

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