Erdal Agar

The effect of ethanol on lipid peroxidation and glutathione level in the brain stem of rat.

The effects of ethanol consumption on the levels of lipid peroxidation (TBARS) and reduced glutathione (GSH) in the brain stem of male rats were investigated. The rats randomly divided into eight groups: control, 10%, 25%, 35% ethanol-consuming groups and four groups given vitamin E. Brain stem GSH levels were significantly decreased by 39.74%, 61.57%, 78.23% in rats consuming 10%, 25% and 35% ethanol, respectively. The level of TBARS was increased six-fold, 12-fold and 17-fold in these groups when compared with the control group. The administration of vitamin E (100 mg/kg/day, i.p) to ethanol-consuming rats for 20 days caused a significant increase in glutathione levels and a significant decrease in lipid peroxidation.

Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide.

The effect of sodium nitroprusside (SNP) on epileptiform activity elicited by administration of penicillin (500 units) into the somatomotor cortex was studied in anaesthetized rats. No epileptiform activity was observed after intracortical microinjection of SNP (5 and 20 nM). Microinjection of penicillin into the somatomotor cortex induced epileptiform activity in electrocorticograms (ECoG). Epileptiform discharges elicited by penicillin were significantly decreased by SNP. The effect of SNP appeared within 1 min of application and lasted for 2-5 min. The inhibitory effect of SNP on epileptiform activity could be prevented by pretreatment with methylene blue (20 nM), a soluble guanylate cyclase inhibitor. Prior injection of haemoglobin (5 microliter), a nitric oxide (NO) scavenger, prevented the anticonvulsant effect of SNP. These results suggest that NO may be an endogenous anticonvulsant substance.

The Effects of Ascorbic Acid on Penicillin-induced Epileptiform Activity in Rats

Summary:  Purpose: Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as α‐tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin‐induced epileptiform activity.

The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats.

Purpose:  Several results support the conclusion that the cannabinoid system has a role in generation and cessation of epileptic seizures. The aim of this study was to evaluate the effects of intracerebroventricular AM‐251 [N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide], a CB1‐receptor antagonist, and ACEA (arachidonyl‐2‐chloroethylamide), a CB1‐receptor agonist, on penicillin‐induced epileptiform activity in rats.

The effect of leptin on penicillin-induced epileptiform activity in rats.

Leptin is an adipose tissue-derived peptide hormone, which acts as a satiety factor to reduce appetite by interactions with hypothalamic neurons. The other possible physiological functions of leptin are still unclear. In this study, we have evaluated dose-dependent effect of leptin on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorymotor cortex. Thirty minutes after penicillin injection, 1, 2 or 10 microg of leptin was administrated intracerebroventricularly (i.c.v.). Leptin (1, 2 or 10 microg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. One or two micrograms of leptin significantly increased the frequency of epileptiform activity in the penicillin-pretreated animals. The high dose of leptin (10 microg) did not significantly change either amplitude or frequency of epileptiform activity. One microgram i.c.v. leptin was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The proconvulsant effects of leptin appeared 90 min after leptin (1 and 2 microg) injection. These data indicate that leptin increases the frequency of penicillin-induced epileptic activity. We speculate that this action of leptin might suggest that leptin may be a proconvulsant substance.

The effects of ethanol consumption on the lipid peroxidation and glutathione levels in the right and left brains of rats

The effects of ethanol consumption on the levels of lipid peroxidation and reduced glutathione (GSH) in the cerebral hemispheres of male rats were investigated. The rats were randomly divided into eight groups: control, 10%, 25%, 35% ethanol-consuming groups, and four groups given vitamin E. The level of lipid peroxidation increased 34.32% (right brain), 35.67% (left brain) in 10% ethanol-consuming rats; 32.05% (right brain), 31.81% (left brain) in 25% ethanol-consuming rats; and 33.45% (right brain), 39.72% (left brain) in 35% ethanol-consuming rats. The GSH level of the right and left brains significantly decreased: 19.39%, 19.56%; 27.58%, 29.34%; 35.34%, 33.22% in rats consuming 10%, 25%, and 35% ethanol, respectively. These effects were partly antagonized by administration of vitamin E (100 mg/kg/day i.p.) to ethanol-consuming rats for 20 days. The results suggested that the cerebral hemispheres of adult rats are susceptible to the oxidative neurotoxic effects of ethanol, which may be blocked by vitamin E

Alcohol-induced oxidative stress and reduction in oxidation by ascorbate/L-cys/ L-met in the testis, ovary, kidney, and lung of rat

Chronic exposure to high doses of alcohol results in many pathophysiologic changes in cellular function caused by the alcohol itself and the effects of its metabolism (ie, generation of acetaldehyde, nicotinamide adenine dinucleotide [NADH], free radicals, and oxidative stress). However, the role of each of these effects on the testis, ovary, kidney, and lung in chronic alcoholism must be investigated. It is hypothesized that cysteine-methionine and vitamin C might neutralize harmful compounds and potentiate the antioxidant capacity of the cell or tissue. In this study, rats were fed regular diets and were maintained in the following groups for 90 days: control group; alcoholic group (2.5 g of 50% ethanol/kg body wt administered intragastrically every other day); and alcoholic with antioxidant supplement group (2.5 g of 50% ethanol plus a solution containing 200 mg vitamin C, 100 mg cysteine, and 100 mg methionine/kg body wt administered intragastrically every other day). After treatment had been completed, rat blood, testis, ovary, kidney, and lung were taken for biochemical analysis. Mean alcohol level in the alcoholic group was raised (by 40%) compared with that in the control group, but it was lower (by 30%) in the antioxidantsupplemented group than in the alcoholic group. In accordance with the levels of alcohol, oxidized protein and lipid content in the testis, ovary, kidney, and lung were low in the control group, higher in the antioxidant-supplemented group, and highest in the alcoholic group. It is interesting to note that levels of glutathione in the testis and lung of the alcoholic group were lower than those in both the control and antioxidant-supplemented groups. In conclusion, chronic alcohol administration led to a significant increase in the level of protein oxidation in the ovary and kidney of rats. Simultaneous intake of ascorbate/l-cys/l-met, along with ethanol, partly attenuated the amount of lipid and protein oxidation that occurred in tissues with oxidative stress caused by alcohol consumption.

The involvement of nitric oxide in the anticonvulsant effects of α-tocopherol on penicillin-induced epileptiform activity in rats

A variety of animal seizure models exist which help to document the effects of alpha-tocopherol (Vitamin E) and specify its action. In the present study, we provide further evidence for the functional involvement of NO in the anticonvulsant effects of alpha-tocopherol on penicillin-induced epileptiform electrocorticographical (ECoG) activity in rats. The epileptiform ECoG activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, the most effective dose of alpha-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Alpha-tocopherol decreased the frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The effect of systemic administration of nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and NO substrates, L-arginine and sodium nitro prusside (SNP) on anticonvulsive effects of alpha-tocopherol was investigated. The administration of L-NAME (60 mg/kg, i.p.) did not influence the frequency of epileptiform ECoG activity while administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) significantly decreased in the penicillin-treated group. The administration of L-NAME (60 mg/kg, i.p.) 10 min after alpha-tocopherol (500 mg/kg, i.m.) application reversed the anticonvulsant effects of alpha-tocopherol. The administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in alpha-tocopherol supplemented group. L-arginine and SNP did not provide an additional anticonvulsant effect in alpha-tocopherol supplemented group. These results support the involvement of the nitric oxide pathway in the anticonvulsant effect of alpha-tocopherol on the penicillin-induced epileptiform ECoG activity.

The role of nitric oxide in the inhibitory effect of ghrelin against penicillin-induced epileptiform activity in rat

Ghrelin, a gastric peptide with key action on food intake, has been recently recognized as a potential antiepileptic agent. In the present study, we investigated the involvement of nitric oxide in the effect of ghrelin on penicillin-induced epileptiform activity in rat. Thirty minutes after penicillin injection, ghrelin, at doses of 0.5, 1, 2 microg, was administered intracerebroventricularly (i.c.v.). Ghrelin, at a dose of 1 microg, significantly decreased the mean frequency of epileptiform activity without changing the amplitude whereas other doses of ghrelin (0.5 and 2 microg) did not alter either the mean of frequency or amplitude of epileptiform activity. The effects of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-l-arginine methyl ester (l-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, l-arginine on the anticonvulsive effects of ghrelin were investigated. The administration of l-NAME (60 mg/kg, i.p.), 15 min before ghrelin (1microg) application, reversed the anti-epileptiform effects of ghrelin whereas 7-NI (40 mg/kg, i.p.) did not influence it. The present study provides electrophysiological evidence that the intracerebroventricular injection of ghrelin has an inhibitory effect against epileptiform activity in the penicillin model of epilepsy. The anti-epileptiform activity of ghrelin was reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ghrelin requires activation of endothelial-NOS/NO route in the brain.

The effect of co-administration of the NMDA blocker with agonist and antagonist of CB1-receptor on penicillin-induced epileptiform activity in rats

Although the activation of CB1-receptor by cannabinoids and block of NMDA receptors are known to decrease seizure severity in epilepsy models, the interaction between these systems remain elusive. Therefore, the present study was initiated to evaluate the possible interactions between cannabinoid compounds and NMDA receptor antagonist in the penicillin-induced epileptiform activity in rat. In the first set of experiments, 30 min after intracortical injection of penicillin, five different doses of memantine (3,5-dimethyl-1-adamantanamine hydrochloride, 1, 2.5, 5, 10 or 20mg/kg) were administered intraperitoneally (i.p.). In the second set of experiments, intracerebroventricular (i.c.v.) AM-251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], (0.25 μg) a CB1-receptor antagonist and ACEA (arachidonyl-2-chloroethylamide), (7.5 μg) a CB1-receptor agonist, were administered 15 min after memantine (i.p.) application. Memantine, NMDA receptor antagonist, at doses of 2.5 and 5mg/kg (i.p.) decreased the mean frequency of penicillin-induced epileptiform activity with a maximal effect at 5mg/kg. Memantine, at the lowest dose (1mg/kg, i.p.) and highest doses (10 and 20mg/kg, i.p.) did not change the frequency of epileptiform activity. ACEA, at a dose of 7.5 μg, also decreased the frequency of epileptiform activity, whereas AM-251, at a dose of 0.25 μg increased the frequency by causing status epilepticus-like activity. The best and earlier anti-epileptiform effects appeared in both the presence of memantine (5mg/kg, i.p.) and ACEA (7.5 μg, i.c.v.), which was blocked by CB1-receptor antagonist, AM-251. The results of the present study provide electrophysiologic evidence for an interaction between cannabinoid system and NMDA receptors, probably via NMDA-mediated Ca(2+) influx in the penicillin-induced epilepsy.