Resveratrol lacks protective activity against acute seizures in mouse models.
Resveratrol (3,4',5-stilbenetriol) is a natural product having diverse anti-inflammatory and antioxidant properties. The compound has a wide spectrum of pharmacological and metabolic activity, including cardioprotective, neuroprotective, anticarcinogenic and anti-aging effects reported in numerous studies. Some reports also suggest potential anticonvulsant properties of resveratrol. In the present study, we used in mice three different seizure models which are routinely applied in preclinical drug discovery. The protective effects of resveratrol were evaluated in the pentylenetetrazole (PTZ), maximal electroshock (MES) and 6-Hz electrical seizure models. Resveratrol (up to 300mg/kg) administered ip (5-60min pre-treatment time) remained without any protective activity against seizures induced in these models. There was only a trend towards a delay in seizure latency, which reached statistical significance after treatment with resveratrol (100mg/kg; 15min) in case of tonic convulsions induced by PTZ. Phenobarbital (PHB, ip, 45min), used as a reference compound, displayed a clear-cut and dose-dependent protection against seizures in all the models. The ED50 values obtained with PHB were as follows: 7.3mg/kg (PTZ model), 13.3mg/kg (MES model) and 29.7mg/kg (6-Hz model). The present data demonstrate that an acute treatment with resveratrol does not provide any significant protection in three seizure models which collectively are able to detect anticonvulsants with diverse mechanisms of action. However, it cannot be excluded that chronic treatment with resveratrol may offer some protection in these or other seizure models.
UCB Pharma, Neurosciences TA, B-1420 Braine-l'Alleud, Belgium; Faculty of Science, University of Sannio, Benevento, Italy.
Francesca
F
Tomaciello
UCB Pharma, Neurosciences TA, B-1420 Braine-l'Alleud, Belgium. Electronic address: Karine.Leclercq@ucb.com.
Karine
K
Leclercq
UCB Pharma, Neurosciences TA, B-1420 Braine-l'Alleud, Belgium.
Rafal M
RM
Kaminski
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D000077185:Resveratrol; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013267:Stilbenes / Q000627:therapeutic use*; D017211:Treatment Failure
D000927:Anticonvulsants; D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol; D010433:Pentylenetetrazole
6-Hz seizure; Antiepileptic drugs; Maximal electroshock; Mice; Pentylenetetrazole; Resveratrol