Understanding the anti-kindling role and its mechanism of Resveratrol in Pentylenetetrazole induced-kindling in a rat model.
BACKGROUND
Resveratrol is a polyphone chemical found in a number of plant species, including peanuts and grapes, but with significant amounts in red wine. In normal plant physiology, Resveratrol is produced as a defensive response to injury or parasitic attacks. Resveratrol has diverse biological properties and actions with potential clinical applications, including anti-inflammatory, antioxidant, anti proliferative, and neuroprotective effects.


OBJECTIVE
The aim of the present study was to explore the effect and mechanism of Resveratrol in Pentylenetetrazole (PTZ) induced kindling in rats.


METHODS
In a PTZ kindled Wistar rat model, different doses of Resveratrol (25mg/kg, 50mg/kg and 75 mg/kg) were administered orally 30 min before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The following parameters were compared between control and various experimental groups: the course of kindling, stages of seizures, histopathological scoring of hippocampus, antioxidant parameters, DNA fragmentation and caspase-3 expression in the hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses.


RESULTS
In the present study, Resveratrol showed dose-dependent anti-seizure effect. Resveratrol (75 mg/kg) significantly increased the latency to myoclonic jerks, clinic seizures as well as generalized tonic-clinic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ induced kindling caused a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with Resveratrol in a dose-dependent manner.


CONCLUSIONS
Our study suggests that Resveratrol has a potential antiepileptogenic effect on PTZ-induced kindling in rats. The possible underlying mechanisms of Resveratrol as an antiepileptic agent may be due to its antioxidative property and neuroprotective effect.
Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. Electronic address: lekhasaha@rediffmail.com.
Lekha
L
Saha
Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Amitava
A
Chakrabarti
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D053148:Caspase 3 / Q000096:biosynthesis; D003292:Convulsants / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology; D007696:Kindling, Neurologic / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis; D051381:Rats; D000077185:Resveratrol; D012640:Seizures / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D013267:Stilbenes / Q000494:pharmacology*
D000927:Anticonvulsants; D000975:Antioxidants; D003292:Convulsants; D013267:Stilbenes; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D000077185:Resveratrol; D010433:Pentylenetetrazole
Antioxidant; Epileptogenesis; Kindling; Pentylenetetrazole; Rat; Resveratrol