Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model.
OBJECTIVE
Epilepsy as well as chronic use of most antiepileptic drugs predisposes to cognitive impairment. Curcumin has been reported to possess antioxidant, anticonvulsant as well as neuroprotective potential. Hence, this study was conducted to evaluate the effect of curcumin against seizures, cognitive impairment and oxidative stress in pentylenetetrazole-induced kindling in rats.


METHODS
The effect of pretreatment with curcumin (100, 200 and 300 mg/kg, orally) on pentylenetetrazole (PTZ)-induced kindling, kindling-induced cognitive impairment and oxidative stress was evaluated. Male Wistar rats were injected PTZ (30 mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Cognitive impairment was assessed using elevated plus maze and passive avoidance test while the oxidative stress parameters (malondialdehyde and glutathione) were estimated in the whole brain at the end of experiments.


RESULTS
PTZ, 30 mg/kg, induced kindling in rats after 31.0±1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with curcumin in a dose-dependent manner.


CONCLUSIONS
The results indicate that pretreatment with curcumin ameliorates seizures, oxidative stress and cognitive impairment in PTZ induced kindling in rats. These results thus suggest the potential of curcumin as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure induced memory impairment.
Mehla
Jogender
J
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi-110029, India.
Reeta
K H
KH
Gupta
Pooja
P
Gupta
Yogendra Kumar
YK
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D000975:Antioxidants; D008315:Malondialdehyde; D005978:Glutathione; D003474:Curcumin; D010433:Pentylenetetrazole