Fenofibrate, a Peroxisome Proliferator-Activated Receptor [alpha] Agonist, Increase PTZ Threshold in Wistar Adult Rat
Abstract number :
4.026
Submission category :
Translational Research-Animal Models
Year :
2006
Submission ID :
6935
Source :
www.aesnet.org
Presentation date :
12/1/2006 12:00:00 AM
Published date :
Nov 30, 2006, 06:00 AM
Authors :
1,2Natacha Porta, 1,2Stephane Auvin, 1,2Cecile Lecointe, 2Regis Bordet, and 1,2Louis Vallee
Peroxisome proliferator-activated receptor [alpha] (PPAR[alpha]) is one of the three subtypes of the nuclear receptor PPAR family. PPAR[alpha] activation by fenofibrate can protect cerebral injury by anti-oxidant and anti-inflammatory mechanisms. In this study, we tested PPAR[alpha] activation on the cerebral excitability before study its potent neuroprotective effects in status epilepticus., Wistar rats (280g-320g) were separated in two groups (n=8). Sham group (Sh) received a complete powder diet ad libidum, while experimental group (F) received powder diet containing 0.2% fenofibrate. After 14 days of treatment, pentylenetetrazole threshold (PTZth) was used to assess anti-convulsive effect. PTZ was dissolved in a saline solution (10 mg/ml) and was infused i.v. at 5 ml/h. Two threshold doses (mg/kg) were studied : the first bilateral forelimb myoclonus and the start of generalized seizure. Liver weights were recorded in each animal to assess that fenofibrate was pharmacologically active. All values are given as mean +/-sem., Rats receiving diet with 0.2% Fenofibrate had an increase of liver weight (liver weight/body weight): 0.063 +/- 0.004 versus 0.036 +/- 0.002 (p=0.001). Myoclonic and seizure PTZ thresholds were increased in F group in comparison to Sh group: myoclonic PTZth were 40.85 +/- 3.06 mg/kg in F group vs. 34.28 +/- 1.26 mg/kg (Sh) (p=0.028); seizure PTZth were 46.85 +/- 3.58 mg/kg in F group vs. 37.29 +/- 1.8 mg/kg (Sh) (p=0.021)., A treatment with 0.2% fenofibrate significantly increases myoclonic and seizure PTZ thresholds suggesting anticonvulsive proprieties. The role of PPAR activation in brain excitability should be investigated., (Supported by AEAC association and NP was supported by the grant [quot]Conseil Régional Nord-Pas-de-Calais et CHRU de Lille[quot].)
Translational Research