• Toxicological Research
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• 제22권3호
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• pp.275-282
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• 2006

In previous our studies, we have reported that eugenol derived from Eugenia caryophyllata(Myrtaceace) exhibits acute N-methyl-D-aspartate(NMDA)- and oxygen/glucose deprivation-induced neurotoxicity in primary cortical cultures and protects hippocampal neurons from global ischemia. In this study, we investigated whether the extracts and fractions of E. caryophyllata or eugenol shows the neuroprotective effects against delayed neuronal injury evoked by NMDA or ${\alpha}$-amino-3-hydroxy-5-methylisoxazole propionate(AMPA), and oxidative damage induced by arachidonic acid-, hydrogen peroxide-, $FeCl_2$/ascorbic acid-, and buthionine sulfoximine(BSO) in primary cortical cultures. We examined the neurotoxicity of eugenol itself in cultures and inhibitory effect of eugenol on NMDA- or kainate(KA)-induced convulsion in BALB/c mice. Each water, methanol extract and methanol fraction of E. caryophyllata was significantly attenuated NMDA-induced delayed neurotoxicity, respectively. Eugenol exhibited a significant inhibitory action against the convulsion evoked by NMDA and KA, and reduced delayed or brief neurotoxicity induced by NMDA, AMPA, and various oxidative injuries. These results suggest that eugenol derived from E. caryophyllata may contribute the neuroprotection against delayed-type excitotoxicity and excitotoxins-mediated convulsion through the amelioration of oxidative stress.

• 동의생리병리학회지
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• 제18권1호
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• pp.206-213
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• 2004

This study was performed to evaluate the anticonvulsant, antioxidant effect of modified formulas Korean traditional medicine Gungchihwadam-Jeon(GCHDJ). The extract of GCHDJ was administered (p.o.) to mice for 14 days in anticonvulsant and antioxidant tests. The pretreatment of GCHDJ extract prohibited the pentylenetrazol(PTZ)-induced convulsion in PTZ-induced convulsion, lowered level of brain r-aminobutyric acid(GABA) was restored by the pretreatment of GCHDJ. Increased level of brain glutamic acid was lowered to normal state by GCHDJ, and increased activity of brain r-aminobutyric acid transaminase(GABA-T) was reduced by GCHDJ. In PTZ-induced convulsion, increased level of brain lipid peroxide was lowered to normal state by the pretreatment of GCHDJ. Increased activity of brain xanthine oxidase(XOD) was lowered to normal state by GCHDJ, and increased activity of brain aldehyde oxidase lowered to normal state by GCHDJ. In PTZ-induced convulsion, increased activities of superoxide dismutase(SOD) and catalase in brain were lowered by the pretreatment of GCHDJ, whereas increased level of glutathione and increased activity of gluthathione peroxidase in brain were not changed significantly. Above results suggest that GCHDJ have anticonvulsant. antioxidant effect. That seems to be strongly related with the levels of GABA, glutamate, lipid peroxide and the activities of GABA-T, XOD, aldehyde oxidase, SOD, catalase in brain tissue. From these results, GCHDJ could be applied to various convulsive disorders.

• Archives of Pharmacal Research
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• 제26권6호
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• pp.487-492
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• 2003

This study investigated the effects of extremely low frequency magnetic fields (ELF-MFs) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. The mice were exposed to either a sham or 20 G ELF-MFs for 24 hours. Convulsants were then administered i.p. at various doses. The seizure induction time and duration were measured and lethal dose ($LD_{50$}) and convulsant dose ($CD_{50}$) of the clonic and tonic convulsion were calculated. The analysis of glutamate, glycine, taurine and GABA of mouse brain was accomplished by HPLC. The mice exposed to ELF-MFs showed moderately higher $CD_{50}.{\;}LD_{50}$ and onset time on the bicuculline-induced seizure. However, the ELF-MFs did not influence them in the NMDA and picrotoxin-induced seizures. After the exposure to MFs exposure, the glutamate level was increased and GABA was decreased significantly in NMDA and picrotoxin-induced seizure. The level of glutamate and GABA were not changed by MFs in bicuculline-induced seizure. These results suggest that ELF-MFs may alter the convulsion susceptibility through GABAergic mechanism with the involvement of the level of glutamate and GABA.

• Journal of Preventive Medicine and Public Health
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• 제19권2호
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• pp.184-192
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• 1986

Since the wide spread application of hyperbaric oxygenation in clinical setting, the problems of oxygen toxicity have been attracting a deep interest from the researchers on hyperbaric medicine as a practical issue. Among extensive research trials, the study on the protective agents against oxygen toxicity occupied one of the most challenging field. As the mechanisms of oxygen toxicity, the role of the oxygen free radicals produced by peroxidation process are strongly accepted by the leading researchers on oxygen toxicity, the probable protective effects of antioxidant against oxygen toxicity are sustaining a sufficient rationale. In this study, the author attempted to evaluate the effect of vitamin E as a protective agent against oxygen toxicity through the observation of death rate, convulsion rate, time to convulsion, and macroscopic and microscopic pathological changes of experimental rats exposed to 100% oxygen at 5 ATA for 120 minutes. The findings observed are as follows: 1) The death rate, convulsion rate, time to convulsion, organ/body weight ratio and microscopic pathological findings were identified as reliable objective and quantitative indices for oxygen toxicity. 2) Vitamin E showed excellent protective effects against CNS and pulmonary oxygen toxicity as a strong antioxidant. The most effective dose seemed to be around 400 mg/kg 3) The results of this study are supporting the oxygen free radical hypothesis on oxygen toxicity.

• 대한한방소아과학회지
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• 제8권1호
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• pp.59-74
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• 1994

The Study was performed on the anticonvulsive effects of Woohwangporyonghwan(WPH) and Woohwangporyonghwan except CINNABARIS and REALGAR(WPHCR) in ICR mice pretreated with strychnine, picrotoxin, and caffeine as convulsive agents, and also was done on the accumulation of Hg & AS in organs of ICR mice by ICP hydride generation method. The results were obtained as follows: 1. WPH and WPHCR group showed significant effect in delaying the onset of convulsion induced by strichine, but time to death was effective only in WPHCR group. 2. WPH and WPHCR group were significantly effective in delaying convulsion induced by picrotoxin, and time to death. 3. The anticonvulsive effect of WPH and WPHCR group was not found convulsion induced by caffeine. 4. The accumulation of Hg, AS in liver and kidney of ICR mice was not determined below 50ng/g and below 80ng/g respectively. From the above results it could be concluded that WPH and WPHCR group were effective in the convulsions induced by strychnine and picrotoxin, although the accumulation of Hg & As in liver and kidney was not proved, further study might be necessary to prove the drug safety of WPH included CINNABARIS and REALGAR.

• 한국한의학연구원논문집
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• 제3권1호
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• pp.199-213
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• 1997

In convulsion state by PTZ in rat, anticonvulsive effect and some of ${\gamma}-aminobutyric$ acid(GABA)-related mechanisms of Buthus extract in brain was experimented. It was inhibited GABA-T activity, lipid peroxide generation and xanthine oxidase activity as scheduled administration in vitro and vivo. And the content of brain glutathione was increased as scheduled administration in rat. In convulsion state by PTZ of previously managed rat by Buthus extract, onset time and duration were non-specific changes but recovery time and severity was remarkably reduced. In conclusion speculated that Buthus extract inhibits convulsion by control of GABA content In brain.

• 생약학회지
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• 제17권1호
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• pp.12-18
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• 1986

In order to investigate experimentally the clinical effects of Choweesungchung-Tang that has been widely used in the cardiovascular and neuropsychogenic disease, experimental studies with experimental animals were carried out. The results of these studies were summarized as follows; Suppressive action was not shown on the convulsion induced by strychnine, but significant effect was noted on the convulsion induced by picrotoxin and caffeine. In acetic acid method, analgesic effect was noted. By the rotor rod and wheel cage method, sedative action was noted. A prolongation of hypnotic time induced by pentobarbital-Na was obtained. Relaxing action was noted remarkably on the ileum of mice, also about mice and guinea-pigs, the same effect was recognized on the smooth muscle of the ileum. The expansion of blood vessels by relaxation of smooth muscle and hypotensive action were noted.

• 동의생리병리학회지
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• 제25권4호
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• pp.614-619
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• 2011

Nelumbo nucifera(NN) is a oriental medicinal herb which has been used traditionally for the treatment of antidiarrhea, sedative action and various brain diseases including convulsion and epilepsy. In order to examine the mechanism of anticonvulsive effect, we treated the methanol extract of NN(100, 200 mg/kg, P.0) to the sleeping time and pentylenetetrazole(PTZ)-induced convulsive mice. The methanol extract of NN prolonged sleep time by pentobarbital. Methanol extracts of NN were not effected the concentration of GABA and GABA-T activity in the brain of PTZ-induced mice. Methanol extracts of NN significantly inhibited the convulsion state as well as the level of lipid peroxidation in the brain. The butanol and dichloromethane fraction of methanol extracts among the others effectively inhibited in vitro lipid peroxidation dose dependently($5.0{\times}10^{-6}\sim2.0{\times}10^{-5}\;g/ml$). These results suggest that the anticonvulsive effect of NN is possibly due to the antioxidative effects of the free radical formation at brain for the PTZ-induced convulsion if it were by due to generating system.

• Toxicological Research
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• 제6권2호
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• pp.143-157
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• 1990

Effective measure to prevent oxygen toxicity is greatly required as there increase chances to be exposed to high oxygen pressure, for example, space travel, deep sea diving and hyperbaric oxygen therapy. In the present study, in an attempt to evaluate glutathione and chlorpromazine as protective agents against oxygen toxicity, effects of the agents were tested on various toxicities (death rate, convulsion rate, time to convulsion, increase in weight of lung and brain and pathological changes in the organs) observed in rats exposed to 5 Absolute Atmosphere (ATA) of 100% oxygen for 120 minute. Glutathione reduced mortality rate and convulsion rate and also markedly suppressed the increase in lung and brain weight. The pathological changes observed in these organs were ameliorated by administration of glutathione. Chlorpromazine also reduced mortality rate but its effects appeared to be limited mainly to pulmonary toxicities. Thus glutathione seems to be more effective than chlorpromazine as a protective agent. The results obtained may support that oxygen toxicity is mediated by oxygen free radicals.

• 대한수의학회지
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• 제39권2호
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• pp.287-293
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• 1999

Isoeugenol, one of the phenylpropanoid derivatives has been known to inhibit the lipid peroxidation via scavenging effect on hydroxyl or superoxide radical production. We examined whether isoeugenol has a inhibitory effect against N-methyl-D-aspartate(NMDA)-, oxygen/glucose deprivation- and xanthine/xanthine oxidase(X/XO)-induced neurotoxicity or NMDA-induced $^{45}Ca^{+2}$ uptake elevation in primary mouse vertical cultures. We also evaluated whether isoeugenol exhibits inhibitory action on NMDA-induced convulsion in mice. Isoeugenol ($30{\sim}300{\mu}M$) attenuated NMDA- and X/XO-induced neurotoxicity by 11~85% and 83~92%, respectively. In the oxyge/glucose deprivation(60 min)-induced neurotoxicity, isoeugenol significantly(p<0.05) reduced by 32% at the maximal concentration. However, it failed to ameliorate NMDA-induced $^{45}Ca^{+2}$ uptake elevation. Isoeugenol(0.5g/kg, i.p.) delayed 6.5 times on the onset time of convulsion evoked by NMDA($0.1{\mu}g$) compared to that of control. These results suggest that the neuroprotective action of isoeugenol may be ascribed to the modulation of massive generation of reactive oxygen species(ROS) occurred during the ischemic or excitotoxic damage, not by directly affecting the NMDA receptor.