To study the oxidative stress induced by lindane in epileptic rats brains and their modulation by neurosteroids.

ABSTRACT

Background: Lindane is pesticide has been shown to affect the nervous system adversely. Previous work has shown that lindane is proconvulsant and neurosteroids (NS) has been shown to be neuroprotective against lindane-induced convulsions. As the mechanisms of lindane in epileptogenesis is not completely understood. The present study was designed to investigate the oxidative stress parameters of lindane toxicity in epileptogenesis and their modulation by NS like allopregnanolone (AP), and 4ʹ-chlorodiazepam (4ʹ-CD) in pentylenetetrazole (PTZ) kindling methods. Methods: Kindling was induced by injecting PTZ (30 mg/kg; s.c.) on alternate days i.e., 3 times in a week. Lindane was also administered (15 mg/kg p.o) on alternate days for 6 weeks. AP (2.5 mg/kg, intaperitoneal [i.p.]) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose was given in kindled rats before lindane. Results: Following per oral administration of lindane for 6 weeks produced signifi cant oxidative stress in epileptic brain. There was an increase in brain malondialdehyde (MDA) level and decrease in reduced glutathione (GSH) levels. AP (2.5 mg/kg, i.p.) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose administration were not able to reverse the effect of chronic exposure of lindane. Conclusion: The result of the present study provides evidence that oxidative stress produced in the brain after chronic exposure of lindane may be the mechanism of epileptogenesis. Though NS have been shown to be neuroprotective, but they failed to reverse chronic oxidative stress produced by lindane. Further studies are required to demonstrate interaction of NS with lindane in oxidative stress.