Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, exerts anticonvulsive properties.
The underlying mechanisms of the ketogenic diet (KD) remain unknown. Involvement of peroxisome proliferator-activated receptor-alpha (PPARalpha) has been suggested. The aim of this study was to assess the anticonvulsant properties of fenofibrate, a PPARalpha 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 PPARalpha activation and others should be investigated. These findings may provide insights into future directions to simplify KD protocols.
Porta
Natacha
N
Department of Pharmacology, Institut de Médecine Prédictive et de Recherche Thérapeutique, Université de Lille-2 et Centre Hospitalier Universitaire, Lille, France.
Vallée
Louis
L
Lecointe
Cécile
C
Bouchaert
Emmanuel
E
Staels
Bart
B
Bordet
Régis
R
Auvin
Stéphane
S
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D055423:Diet, Ketogenic / Q000379:methods; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011345:Fenofibrate / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007657:Ketone Bodies / Q000097:blood; D018021:Lithium Chloride; D008099:Liver / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists*; D010433:Pentylenetetrazole; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D000960:Hypolipidemic Agents; D007657:Ketone Bodies; D047493:PPAR alpha; D010862:Pilocarpine; D018021:Lithium Chloride; D020155:3-Hydroxybutyric Acid; D011345:Fenofibrate; D010433:Pentylenetetrazole