Ciprofibrate — racemate and enantiomers: Effects of a four-week treatment on male inbred Fischer rats. A biochemical and morphological study

Klinger, W; Lupp, Amelie; Karge, E.; Oelschläger, H.; Rothley, D; Danz, M.; Linss, W; Lobel, Susan M.; Deufel, Thomas; Müller, M.; Klinger, Matthias; Kühnel, Wolfgang

doi:10.1016/s0940-2993(98)80010-9

Cited by 3 publications

(1 citation statement)

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“…This is not surprising when considering that fenofibrate activates nuclear receptors that increase DNA transcription and protein synthesis. Similarly, in nondiabetic rats, fenofibrate increased the kidney weight/body weight ratio compared with untreated rats, which has been reported for Fischer rats (Klinger et al, 1998). In our study, both control and diabetic rats treated with fenofibrate exhibited less weight gain compared with their untreated counterparts, which has also been reported and contributes to the increased kidney weight/body weight ratio.…”

Section: Fenofibrate and Renal Cox-2 In Diabetes 661supporting

confidence: 87%

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

Chen¹,

Quilley²

2007

J Pharmacol Exp Ther

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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 ␣ 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 agematched control rats (n ϭ 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 Ϯ 0.7 versus 1.9 Ϯ 0.7 ng/min) and reduced by fenofibrate to 0.6 Ϯ 0.2 ng/min. A similar pattern was obtained for AA-stimulated release of 6-ketoPGF 1␣ . 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 Ϯ 0.4 versus 1.15 Ϯ 0.1 ml/min for control, and reduced by fenofibrate treatment to 1.87 Ϯ 0.3 ml/min. These results show that fenofibrate treatment of diabetic rats decreases renal COX-2 expression, possibly by reducing nitrosative stress, and is associated with a reduction of the enhanced GFR.

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Section: Fenofibrate and Renal Cox-2 In Diabetes 661supporting

confidence: 87%