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Fenofibrate, a peroxisome proliferator–activated receptor‐α agonist, exerts anticonvulsive properties
Author(s) -
Porta Natacha,
Vallée Louis,
Lecointe Cécile,
Bouchaert Emmanuel,
Staels Bart,
Bordet Régis,
Auvin Stéphane
Publication year - 2009
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2008.01901.x
Subject(s) - status epilepticus , fenofibrate , pilocarpine , pentylenetetrazol , agonist , ketogenic diet , anticonvulsant , endocrinology , medicine , pharmacology , receptor , epilepsy , chemistry , seizure threshold , psychiatry
Summary The underlying mechanisms of the ketogenic diet (KD) remain unknown. Involvement of peroxisome proliferator–activated receptor‐α (PPARα) has been suggested. The aim of this study was to assess the anticonvulsant properties of fenofibrate, a PPARα agonist. Wistar rats were fed at libitum during 14 days by regular diet, KD, regular diet containing 0.2% fenofibrate (F), or KD containing 0.2% fenofibrate (KD + F). Pentylenetetrazol (PTZ) threshold and latencies to the onset of status epilepticus induced by lithium–pilocarpine were used to assess diet treatments with anticonvulsive effects. Myoclonic and generalized seizure PTZ thresholds were increased in F‐ and KD‐treated animals in comparison to control. No difference was observed between KD + F group and the others groups (control, F, KD). Latencies to the onset of status epilepticus were increased in F and KD groups compared to control. Fenofibrate exerts anticonvulsive properties comparable to KD in adult rats using PTZ and lithium–pilocarpine models. The underlying mechanisms such as PPARα activation and others should be investigated. These findings may provide insights into future directions to simplify KD protocols.