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Carbamate pesticides like propoxur have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was designed to explore the modulation of the effects of propoxur over cognitive function by progesterone (PROG) and 4'-chlorodiazepam (4CD). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, transfer latency (TL) on a plus maze and spatial navigation test on Morris water maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL and spatial navigation test was found for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 as compared with control. One-week treatment with 4CD (0.5 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, spatial navigation test as well as TL; whereas, PROG failed to modulate this effect at a dose of 15 mg/kg/d, i.p. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with 4CD at the above dose attenuated the effect of propoxur on oxidative stress whereas PROG (15 mg/kg/d; i.p.) failed to influence the same. The results of the present study thus show that 4-CD has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used in dental care as an antiseptic and analgesic. The study aims to evaluate the effect of clove oil on experimental models of pain and cognition in mice. To observe the acute effects of clove oil at different doses, the elevated plus maze was used for the assessment of cognition, and the tail flick and formalin tests were used for the study of pain. The formalin test showed that clove oil (0.1 ml/kg, i.p.) demonstrated significantly reduced pain response in both the phases. The lower doses (0.025 and 0.05 ml/kg, i.p.) reduced the formalin-induced pain response significantly in the second phase only. The tail-flick test showed variable response. The dose 0.1 ml/kg, clove oil, significantly decreased the tail-flick latency at 30 min and this effect was reversed by naloxone (1 mg/kg). On the contrary, the dose 0.025 ml/kg of clove oil, at 30 and 60 min increased the mean tail-flick latency compared to control group, but this effect was not statistically significant. Yet naloxone significantly (p

The present study was carried out to investigate the effect of trimetazidine on the course of pentylenetetrazole (PTZ)-induced chemical kindling and oxidative stress markers in PTZ-kindled mice. Kindling was induced by repeated injections of a subconvulsive dose of PTZ (30 mg⁄kg, i.p.) on alternate days for 5 weeks or until stage 4 of the seizure score was evoked on three consecutive administrations. Trimetazidine was administered daily in three doses (5, 10 and 20 mg/kg) per orally (p.o.) along with alternate-day PTZ. Following PTZ kindling, oxidative stress parameters, i.e. levels of malondialdehyde (MDA) and reduced glutathione (GSH), were assessed in isolated homogenized whole brain tissue. The results showed that PTZ treatment progressively increased the seizure score in control mice. Biochemical analysis revealed a significant increase in MDA levels and decreased GSH levels in the brain homogenate of PTZ-kindled mice. Daily treatment with trimetazidine in doses of 10 and 20 mg/kg significantly decreased the PTZ-induced seizure score. However, a low dose of trimetazidine (5 mg/kg) failed to improve the seizure score. Pretreatment of trimetazidine in all doses showed an ameliorating effect on biochemical alteration induced by PTZ treatment. The results of the present study indicate the potential anticonvulsant activity of trimetazidine against PTZ-induced kindling in mice.

Phosphamidon (PHOS) has been shown to affect nervous system adversely. The present study was designed to explore the modulation of the effects of PHOS on convulsions by neurosteroids, progesterone (PROG), and 4′-chlorodiazepam (4′-CD), in both acute and chronic seizure models. In acute study, seizures were induced by either pentylenetetrazole (PTZ) injection or maximal electroshock seizures, while in the chronic study, kindling was induced by injecting PTZ (30 mg/kg, s.c.) on alternate days three times in a week. Oxidative stress was assessed in the brain by measuring the levels of malondialdehyde (MDA), acetylcholinesterase (AChE), and non-protein thiol (NP-SH). PROG and 4′-CD were able to modulate the PHOS-induced convulsions in acute PTZ convulsions as well as in chronic kindling model. However, they failed to reverse the derangements in oxidative stress parameters of MDA and NP-SH produced by PHOS in kindled animals. PROG significantly increased the AChE activity in untreated rats, while PROG and 4′-CD reversed the AChE activity inhibition induced by PHOS. The study indicates a possible anticonvulsive mechanism of neurosteroids, since both PROG and 4′-CD reversed PHOS-induced inhibition of AChE activity. The neurosteroids seem to play a protective role in PHOS-induced convulsions besides their antioxidant property.