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

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.

Attenuation of the effect of lindane on immune responses and oxidative stress by Ocimum sanctum seed oil (OSSO) in rats.

Present study was done to evaluate the effect of Ocimum sanctum seed oil (OSSO) on the immunotoxicity and oxidative activity of lindane in rats. Rats were divided into four groups (n = 8) and were treated with lindane (10 mg/kg, po) and/or OSSO (1 mg/kg, po) during the study period. Humoral immunity was assessed by measuring haemagglutination titre to sheep red blood cells (SRBC) and delayed type hypersensitivity (DTH) was assessed by measuring foot pad thickness. Lindane showed significant decrease in anti-SRBC antibody titre and also decreased percentage change in foot pad thickness in DTH response as compared to control group. OSSO per se produced significant increase in anti-SRBC antibody titre, but did not produce significant change in the foot pad thickness as compared to control group. However, it significantly antagonized the effect of lindane on the anti-SRBC antibody titre and foot pad thickness parameters. Lindane produced oxidative stress as indicated by increase in the levels of MDA and decrease in GSH levels. Treatment with OSSO per se showed antioxidant activity and also reversed the oxidative stress produced by lindane. The results suggest that OSSO can attenuate the immunotoxicity and oxidative stress produced by lindane.

Antidiabetic, antihypercholesterolaemic and antioxidant effect of Ocimum sanctum (Linn) seed oil.

Antihyperlipidaemic and antioxidant effect of Ocimum sanctum Linn. seed oil (OSSO) was investigated in rabbits. Administration of OSSO (0.8 g/kg body weight/day) for four weeks, in cholesterol (100 mg/kg body weight/day) fed rabbits significantly decreased serum cholesterol, triacylglycerol and LDL-+VLDL-cholesterol as compared to untreated cholesterol fed group. There was significant fall in atherogenic index in OSSO treated group. In addition, treatment with OSSO decreased lipid peroxidation and increased reduced glutathione content in blood. Antidiabetic effect of O. sanctum seed oil was evaluated in alloxan diabetic rabbits. Two weeks treatment of diabetic rabbits with OSSO (0.8 gm/kg/day) showed no significant hypoglycaemic effect. Results of the present study show that OSSO has hypocholesterolaemic and antioxidant effects but it does not have antidiabetic effect.

Involvement of GABA-A receptor chloride channel complex in isolation stress-induced free choice ethanol consumption in rats.

The present study revealed the effect of diazepam, a benzodiazepine, and progesterone, a pregnane precursor of neurosteroids, which act via modulating GABA-A chloride channel complex on the isolation stress-induced free choice ethanol consumption in adult rats. Isolation stress for 24 hr over a period of 6 days produced a significant increase in ethanol consumption, which persisted during the 6-day recovery period. Pretreating the animals with diazepam (5 mg/kg, i.p.), or progesterone (5 mg/kg, i.p.), blocked the isolation stress-induced increase in ethanol consumption. Bicuculline (2 mg/kg, i.p.), a GABA-A receptor antagonist significantly attenuated the effect of both diazepam and progesterone on stress-induced modulation of ethanol consumption. Isolation stress also caused an increase in total fluid consumption, which was antagonised by both diazepam and progesterone. Like ethanol consumption, this effect of diazepam and progesterone on isolation stress-induced increase in total fluid consumption was attenuated by bicuculline. Neither diazepam nor progesterone produced an increase in ethanol consumption in non-stressed rats. However, unlike diazepam, progesterone administration to non-stressed rats caused a significant increase in total fluid consumption. Results of the present study thus show that GABAergic mechanisms may be playing an important role in isolation stress-induced increase in ethanol consumption.