Gobind Garg

Effect of Carbamazepine and Lamotrigine on Cognitive Function and Oxidative Stress in Brain during Chemical Epileptogenesis in Rats

The present study assessed the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemically induced epileptogenesis in rats. Epileptogenesis was induced by administration of pentylenetetrazole (30 mg/kg, s.c.) on alternate days (three times/week) for 9-11 weeks or until stage 4 of seizure score was achieved. The neurobehavioural parameters used for cognitive assessment were step-down latency in continuous avoidance apparatus and transfer latency in elevated plus maze test paradigm. Carbamazepine and lamotrigine were administered intraperitoneally in doses of 60 mg/kg and 25 mg/kg, respectively, according to the groups, once a day for 11 weeks. Oxidative stress was assessed in isolated homogenized whole brain samples and estimated for the levels of malondialdehyde, reduced glutathione, catalase and superoxide dismutase. The results showed that lamotrigine did not produce any change in cognitive function, while carbamazepine produced cognitive dysfunction. Cognitive decline seen in the carbamazepine-treated pentylenetetrazole-kindled group was also associated with increased oxidative stress. Lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group.

Reversal of propoxur-induced impairment of step-down passive avoidance, transfer latency and oxidative stress by piracetam and ascorbic acid in rats.

Propoxur, a carbamate pesticide has been shown to adversely affect memory and induce oxidative stress. The present study was designed to correlate the effect of propoxur, piracetam (a nootropic drug) and ascorbic acid (an antioxidant) on oxidative stress and cognitive function. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and non-protein thiol (NP-SH) levels. A significant reduction in SDL and prolongation of TL was found for the propoxur-treated group at weeks 6 and 7 as compared with control (p<0.001). One week treatment by piracetam (400mg/kg/d, i.p.) or ascorbic acid (120mg/kg/d, i.p.) antagonized the effect of propoxur on SDL as well as TL. Both piracetam and ascorbic acid attenuated the propoxur-induced increase in brain MDA levels and decrease in brain NP-SH levels. Results of the present study show that ascorbic acid and piracetam have the potential to reverse cognitive dysfunction and oxidative stress induced by propoxur in the brain.

Interaction of morphine and potassium channel openers on experimental models of pain in mice

Combination of opioid and potassium channel openers holds immense potential for the treatment for most acute and chronic pain. Therefore, the study was performed to assess the interaction between morphine and K+‐channel openers. Swiss albino mice of either sex weighing between 25 and 30 g were used for the study. The study assesses the interaction between morphine and K+‐channel openers (cromakalim, diazoxide and minoxidil), when administered intraperitoneally, using formalin and tail‐flick tests in mice. Both morphine and K+‐channel openers produced significant antinociception at higher doses in both the behavioral tests. Lower doses of morphine and K+‐channel openers had no significant effect on tail‐flick latency, while the same drugs had significant antinociceptive effect on formalin test. The combination of lower doses of morphine and K+‐openers was observed to have significant antinociceptive effect in both the behavioral tests. Administration of naloxone prior to morphine or K+‐channel openers antagonized the analgesic effect of morphine but not of K+‐channel openers, whereas prior administration of glibenclamide antagonized the effect of both morphine and K+‐channel openers. The study, therefore, suggests that the common site of action of morphine and K+‐channel openers is at the levels of K+‐channels rather than at the level of receptors. However, such interaction depends on the differential sensitivity to different pain stimulus.

Protective role of melatonin in myocardial oxidative damage induced by mercury in murine model

This study was designed to investigate the electrophysiological, hemodynamic and biochemical parameters of mercuric chloride and methylmercury exposure on cardiovascular functions and its modulation by melatonin in vivo. Wistar albino rats were divided into six group containing 10 animals each. Mercuric chloride (3.75 µM/L) in drinking water and methylmercury (0.5 mg/kg/day) through gavage, given for 1 month, induced a statistically significant increase (p < 0.001) in left ventricular end diastolic pressure, blood and cardiac tissue mercury content and myocardial lipid peroxides compared to control. Significant attenuation (p < 0.05) of baroreflex sensitivity and depletion of myocardial endogenous antioxidants (p < 0.001) viz. Reduced glutathione (GSH) and superoxide dismutase (SOD) were also found in the mercury-exposed groups as compared to control group. Mercury exposure followed by subacute treatment with melatonin (4 µg/mL/day) in drinking water for 1 month significantly lowered (p < 0.01) left ventricular end diastolic pressure and lipid peroxide levels and increased baroreceptor sensitivity (p < 0.001) and also levels of GSH and SOD (p < 0.001) as compared to mercury-exposed rats. The results of our study provide clear evidence that elevated oxidative stress and altered baroreflex mechanisms caused by mercury intoxication may be the contributing factors responsible for impairment of cardiovascular functions and melatonin may exhibit cardioprotective property against subacute heavy metal intoxication and enhance the antioxidant defense against mercury-induced oxidative myocardial injury in rats.