• Journal of Neurocritical Care
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• v.7 no.2
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• pp.104-110
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• 2014

Background: Cefepime is a fourth-generation cephalosporin widely used for empiric treatment of severe infections. Neurotoxicity by cefepime have been reported due to γ-aminobutyric acid A receptor inhibition or other mechanisms. The aim of this study was to evaluate the risk factors for cefepime-induced neurotoxicity between group showing cefepime-induced neurotoxicity and group without neurotoxicity. Methods: From Jan 2005 to June 2010, a total of 2,461 patients (older than 20) who used cefepime were considered in this study. We compared patients who developed cefepime-induced neurotoxicity (patient group, n=21) to patients who had no cefepime-induced neurotoxicity (control group, n=31). We analyzed demographic, underlying diseases, and metabolic parameters before cefepime treatment and during cefepime treatment between the two groups. Statistical analysis was performed using SPSS 18 software. Results: Of the total 2461 patients, 21 (0.85%) were diagnosed with cefepime-induced neurotoxicity. Impaired glomerular filtration rate (GFR at 15-30 ml/min) before cefepime use were significantly (P<0.05) higher risk for developing cefepime-induced neurotoxicity in patient group compared to that in the control group. Age, sex, and other metabolic parameters except GFR before and during, usage of cefepime did not show any statistical difference between the two groups. Conclusion: The present study revealed that cefepime-induced neurotoxicity was prone to develop in patients with impaired renal function before cefepime usage.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4465-4468
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• 2015

Background: As the third generation of platinum-based antineoplastic agent aginst gastrointestinal cancer, oxaliplatin is considered to be associated with severe sensory neurotoxicity. Acorrding to previous studies, vitaminE, intravenous Ca/Mg and glutamine may partly reduce the incidence and severity of oxaliplatin-induced neurotoxicity. The aim of this study was to investigate the safety and efficacy of analgecine for preventing oxaliplatin-induced neurotoxicity in the patients with gastrointestinal tumors. Method: In this study, patients undergoing oxaliplatin-based chemotherapy were assigned to analgecine (experimental) group or control group. Analgecine 6ml was administered once a day for seven days from the day of oxaliplatin treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) was used to evaluate oxaliplatin-induced neurotoxicity. The incidence rates and grade of neurotoxicity of patients were assessed before and during (after four and eight cycles) treatment. Results: Totally, 82 patients were enrolled in this study, 42 in experimental group and 40 in control group. The occurrence of each grade neurotoxicity in the experimental group was significantly lower than that in control group. The overall occurrence rate was 31% vs 55% (P=0.043) after 4 cycles and 52% vs 75% (P=0.050) after 8 cycles. Conclusion: Analgecine appears could be effective in reducing oxaliplatin-induced neurotoxicity and be applicated for patients with gastrointestinal tumors who would be treated with oxaliplatin-based chemotherapy.

• Korean Journal of Pharmacognosy
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• v.23 no.4
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• pp.259-263
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• 1992

The neuroprotective effect of betaine, one of the components of Lycii Fructus, on glutamate-induced neurotoxicity in primary cultured chicken brain cells were examined. Betaine was found to attenuate glutamate-induced neurotoxicity at the concentration of $5{\sim}10{\;}mM$ in both morphological and chemical aspects. The pretreatment of chicken brain cells with $5{\sim}10{\;}mM$betaine for 2hr at the 12 th day of culture before the 40min-exposure to $500\;{\mu}M$ glutamate significantly increased the survival rate of nerve cells in chicken brain. Betaine could also raise the decreased LDH-level in chicken brain cells which were induced neurotoxicity with $100\;{\mu}M$ glutamate. LDH value was decreased to 63% of control level in chicken brain cells at the time of 48 hr after the exposure to glutamate. However, the pretreatment of chicken brain cells with 5 mM betaine for 2 hr before the exposure to glutamate prevent the decrease of LDH in cells showing 90% of control level. Nevertheless, the remarkable neuroprotective effect of betaine on the glutamate-induced neurotoxicity in cultured chicken brain cells could not be observed when betaine was simultaneously administrated with glutamate.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.46-46
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• 1993

The neuroprotective effect of betaine, one of the , components of Lycii Fructus, on glutamate-induced neurotoxicity in primary cultured chicken brain cells were examined. Betaine was found to attenuate glutamate-induced neurotoxicity at the concentration of 5-10 mM in both morphological and chemical aspects. The pretreament of chicken brain cells with 5-10 mM betaine for 2 hr at the 12th day of culture before the 40 min-exposure to 500${\mu}$M glutamate significantly increased the survival rate of nerve cells in chicken brain. Betaine could also raise the decreased LDH-level due to the neurotoxicity induced with 100${\mu}$M glutamate in chicken braill cells. LDH value was decreased to 63％ of control level in chicken brain cells at the time of 48 hr after the exposure to glutamate. However, the pretreament of chicken brain cells with 5 mM betaine for 2 hr before the exposure to glutamate could prevent the decrease of LDH-level in brain cells showing 90％ of control level. Nevertheless, tile remarkable neuroprotective effect of betaine on the glutamate-inducer in neurotoxicity in cultured chicken brain cells could not be observe when betaine was simultaneously administered with glutamate.

• The Journal of Korean Medicine
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• v.21 no.1
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• pp.29-39
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• 2000

In order to elucidate the toxic mechanism of oxygen radicals in cultured mouse spinal sensory neurons, cytotoxic effect of oxygen radicals was evaluated by M1T assay and NR assay. In addition, protective effect of Sopunghwalhyultang(SPHHT) water extract on oxidant-induced neurotoxicity was investigated on these cultures. Spinal sensory neurons derived from mice were cultured in mediums containing various concentrations of Xanthine Oxidase / Hypoxanthine(XO/HX). Cell viability was measured by MTT assay and NR assay. XO/HX-mediated oxygen radicals remarkably decreased cell viability of cultured spinal sensory neurons in a dose-and time-dependent manner. And also, SPHHT blocked XO/HX-induced neurotoxicity in these cultures. These results suggest that oxygen radicals are toxic and SPHHT are effective in blocking against the oxidant-induced neurotoxicity in cultures of spinal sensory neurons of mice.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.177-183
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• 2000

We examined the neurotoxic effects of 3 glutathione (GSH) depletors, buthionine sulfoximine (BSO), diethyl maleate (DEM) and phorone, under the presence of trolox, cycloheximide (CHX), pyrrolidine dithiocarbamate (PDTC) or MK-801 in primary mouse cortical cell cultures. All three depletors induced neuronal death in dose and exposure time dependent manner, and decreased total cellular GSH contents. The patterns of the neuronal death and the GSH decrements were dependent on the individual agents. DEM $(200\;{\mu}M)$ induced rapid and irreversible decrement of the GSH. BSO (1 mM) also decreased the GSH irreversibly but the rate of decrement was more progressive than that of DEM. Phorone (1 mM) reduced the GSH content to 40% by 4 hr exposure, that is comparable to the decrement of BSO, but the GSH recovered and reached over the control value by 36 hr exposure. BSO showed a minimal neurotoxicity $(0{\sim}10%)$ at the end of 24 hr exposure, but marked neuronal cell death at the end of 48 hr exposure. The BSO (1 mM)-induced neurotoxicity was markedly inhibited by trolox or CHX and partially attenuated by MK-801. DEM induced dose-dependent cytotoxicity at the end of 24 hr exposure. Over the doses of $400\;{\mu}M,$ glial toxicity also appeared. DEM $(200\;{\mu}M)-induced$ neurotoxicity was markedly inhibited by trolox or PDTC. Phorone (1 mM) induced moderate neurotoxicity (40%) at the end of 48 hr exposure. Only CHX showed significant inhibitory effect on the phorone-induced neurotoxicity. These results suggest that the GSH depletors induce neuronal injury via different mechanisms and that GSH depletors should be carefully employed in the researches of neuronal oxidative injuries.

• Archives of Pharmacal Research
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• v.17 no.5
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• pp.343-347
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• 1994

Effects of betaine on glutamate-induced neurotoxicity were examined on primary culturs of chicken embryonic brain cells and on rat cortical cultures. Betaine was found to attenuate glutamate-induced neurotoxicity both morphologically and biochemically. A 30 min exposure of chicken embryonic brain cells cultured for 12 days to 500 .mu.M glutamate produced wide-spread acute neuronal swelling and neurtic fragmentation. A 2-h pretreatment of cultured chicken embryonic brain cells with i mM betaine prior to a 30 min exposure to 500 , mu, M glutamate significantly raised the survival rate of neurons in the culture. When chicken embryonic brain cells were pretreated for 2 h with i mM betaine followed by exposure to 100 .mu.M glutamate for 42 h, lactate dehydrogenase levels within the cells remained at 62% of .mu.M untreated control values while glutamate-treated control fell to 0% lactate dehydrogenase. Betaine also exerted attenuating effects on N-methyl-D-asparte-, kainate-and quisqualate-induced neurotoxicity in a similar manner to that observed with glutamate. Similar neuroprotective effects of betaine with rat cortical cultures.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.613-619
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• 2000

The author examined whether the methanol extracts of Opuntia ficus-indica fruit and Saururus chinensis have the inhibitory action on xanthine/xanthine oxidase (X/XO)-, $FeCl_2/ascorbic$ acid- and arachidonic acid-induced neurotoxicity in mouse cortical cell cultures. The methanol extracts ($10\;{\mu}g/ml{\sim}1\;mg/ml$) of Opuntia ficus-indica and Saururus chinensis were exhibited 53-89% and $48{\sim}100%$ inhibitory action on X/XO-induced neurotoxicity, respectively. At the range of same concentration, both extracts also attenuated the $FeCl_2/ascorbic$ acid-induced neurotoxicity by $35{\sim}100%$ and $15{\sim}98%$, respectively. In arachidonic acid neurotoxicity, the methanol extract (1 mg/ml) of Opuntia ficus-indica and Saururus chinensis reduced neuronal injury by 22% and 38%, respectively. These results suggest that Opuntia ficus-indica fruit and Saururus chinensis may contribute the neuroprotection in certain free radical-mediated neuronal injury.

• Korean Journal of Veterinary Research
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• v.39 no.2
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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.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.64-70
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• 2000

Effects of Rhizoma gastrodiae on glucose oxidase-induced neurotoxicity was investigated in cultured newborn mouse spinal dorsal root ganglion(DRG) neurons that were treated in the media with or without glucose oxidase. In addition, the protective effect of Rhizoma gastrodiae extract against glucose oxidase-induced neurotoxicity was examined. Cytotoxic values were expressed as a percentage of number of living cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In this paper, exposure of neurons to glucose oxidase resulted in a significant call death in a dose- and time-dependent manners in DRG neuron cultures. The decrease in cell viability induced by the glucose oxidase was blocked by Rhizoma gastrodiae extract. These results indicate that the neuroprotective effect of Rhizoma gastrodiae extract against glucose oxidase-induced neurotoxicity may result from a prevention or attenuation of oxidative damage induced by glucose oxidase.