• Journal of The Korean Society of Clinical Toxicology
• /
• v.18 no.1
• /
• pp.34-41
• /
• 2020

Purpose: This study evaluated aggressive hyperbaric oxygen therapy (HBOT) by understanding various exposure routes of acute carbon monoxide (CO) poisoning, the risk factors causing acute cardiovascular, and neurological toxicity caused by poisoning. Methods: A retrospective study was conducted based on the medical records of 417 acute CO poisoning patients who visited the emergency care unit from March 2017 to August 2019. The exposure routes, HBOT performance, age, sex, medical history (hypertension, diabetes mellitus, ischemic heart disease, heart failure), intentionality, loss of consciousness (LOC), intake with alcohol or sedatives, and initial test results (carboxyhemoglobin (COHb), troponin-I, electrocardiography, echocardiography, brain MRI) were examined. Comparative analysis of the clinical information was conducted between the groups that showed acute cardiovascular toxicity and neurological toxicity, and groups that did not. Results: Among 417 patients diagnosed with acute CO poisoning, 201 cases (48.2%) were intentional, and charcoal briquette was the most common route (169 patients (40.5%)). Two hundred sixteen cases (51.8%) were accidental, and fire was the most common route (135 patients (32.4%)). The exposure route was more diverse with accidental poisoning. Three hundred ninety-nine patients were studied for acute cardiovascular toxicity, and 62 patients (15.5%) were confirmed to be positive. The result was statistically significant in intentionality, LOC, combined sedatives, initial COHb, HTN, and IHD. One hundred two patients were studied for acute neurological toxicity, which was observed in 26 patients (25.5%). The result was statistically significant in age and LOC. Conclusion: Active HBOT should be performed to minimize damage to the major organs by identifying the various exposure routes of CO poisoning, risk factors for acute cardiovascular toxicity (intentionality, LOC, combined sedatives, initial COHb, HTN, IHD), and the risk factors for acute neurological toxicity (age, LOC).

• Journal of Digestive Cancer Research
• /
• v.5 no.1
• /
• pp.62-65
• /
• 2017

Pancreatic cancer is an aggressive disease and despite the efforts of the past few decades, the 5-year overall survival (OS) rate remains disappointing and does not exceed 10% in Korea. Especially, only 15-20% of patients are candidates for surgical resection because most patients are diagnosed with locally advanced or metastatic disease, and their only treatment approach is palliative chemotherapy. Since the first chemo-regimen of Gemcitabine and Nanoparticle albumin bound (nab) - paclitaxel was brought to clinical practice in 2013, the improvement in overall survival, progression-free survival, and response rate was achieved in patients with metastatic pancreatic adenocarcinoma. We report the case of a young patient with cardiogenic shock accompanied by multi-organ failure after 4^th cycle Gemcitabine and nab-paclitaxel chemotherapy with partial response.

• Journal of The Korean Society of Clinical Toxicology
• /
• v.21 no.2
• /
• pp.81-91
• /
• 2023

Purpose: Edible insect extracts have been used as an alternative source for medicinal supplements due to their significant antioxidative and anti-inflammatory activity. Recent studies have reported that anti-microbial peptides from insects have neuroprotective effects on dopamine toxins. The purpose of this study was to investigate the protective functions of mealworm (Tenebrio molitor) extract (MWE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cellular toxicity in SH-SY5Y neuroblastoma cells. Methods: Cellular toxicity induced by the MPTP toxin and the impact of MWE on cell survival were analyzed using MTT assays. DAPI staining was performed to observe apoptotic phenomena caused by MPTP. Changes in caspase-3 activity and protein expression were observed using enzyme activity assays and western blot assays, respectively. Results: MWE exerted significant antioxidant activity, which was measured by both DPPH and ABTS radical assays, with a dose-dependent relationship. Furthermore, MWE resulted in cellular proliferation in SHSY5Y cells in a dose-dependent manner. Furthermore, MWE pretreatment significantly inhibited MPTP-induced cytotoxicity, with a dose-dependent relationship. The morphological characteristics of apoptosis and increased reactive oxygen species induced by MPTP were also significantly reduced by MWE pretreatment. Conclusion: MWE treatment significantly attenuated MPTP-induced changes in the levels of proteins associated with apoptosis, such as caspase-3 and PARP. These findings suggest that MWE exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells subject to MPTP-induced dopaminergic neurodegeneration.

• Journal of Life Science
• /
• v.20 no.7
• /
• pp.1121-1126
• /
• 2010

The oxidative stress induced by reactive oxygen species (ROS) may play an important role in the pathogenesis of neurodegenerative diseases. In this study, we investigated the neuroprotective effects of methanolic extracts of Prunella Spica (PSE) against $H_2O_2$-induced oxidative stress in PC12 cells. The cells exposed to $H_2O_2$-induced oxidative stress were treated with various concentrations of PSE; this treatment resulted in the induction of a dose-dependent protective effect, which was evidenced by the results of MTT reduction assay, lactate dehydrogenase (LDH) release assay, morphological assay, and colony-formation assay. Interestingly, we also observed reduction of apoptotic bodies in the Hoechst staining and flow cytometric analysis. These data show that apoptosis was significantly suppressed in the PC12 cells that were exposed to $H_2O_2$-induced oxidative stress and treated with PSE. These results suggest that Prunella Spica could be a new potential protective agent against $H_2O_2$-induced oxidative stress.

• Analytical Science and Technology
• /
• v.24 no.6
• /
• pp.544-555
• /
• 2011

The acute toxicity in the rainbow trout (Oncorhynchus mykiss) was analyzed and predicted using quantitative structure-activity relationships (QSAR). The aquatic toxicity, 96h $LC_{50}$ (median lethal concentration) of 275 organic pesticides, was obtained from EU-funded project DEMETRA. Prediction models were derived from 558 2D molecular descriptors, calculated in PreADMET. The linear (multiple linear regression) and nonlinear (support vector machine and artificial neural network) learning methods were optimized by taking into account the statistical parameters between the experimental and predicted p$LC_{50}$. After preprocessing, population based forward selection were used to select the best subsets of descriptors in the learning methods including 5-fold cross-validation procedure. The support vector machine model was used as the best model ($R^2_{CV}$=0.677, RMSECV=0.887, MSECV=0.674) and also correctly classified 87% for the training set according to EU regulation criteria. The MLR model could describe the structural characteristics of toxic chemicals and interaction with lipid membrane of fish. All the developed models were validated by 5 fold cross-validation and Y-scrambling test.

• Journal of Life Science
• /
• v.19 no.4
• /
• pp.449-456
• /
• 2009

Murine Neuro-2a (N2a) cells have been widely used for the investigation of neuronal differentiation, trophic interaction and neurotoxic effects of various compounds and their associated mechanisms. N2a cells have many genomic variations such as gains or losses in DNA copy number, similar to other neuroblastoma cells, and no systematic or high-resolution studies of their genome-wide chromosomal aberrations have been reported. Presently, we conducted a systematic genome-wide determination of chromosomal aberrations in N2a cells using a high-throughput, oligonucleotide array-based comparative genomic hybridization (oaCGH) technique. A hidden Markov Model was employed to assign each genomic oligonucleotide to a DNA copy number state: double loss, single loss, normal, gain, double gain and amplification. Unlike most neuroblastoma cells, Mycn amplification was not observed in N2a cells. In addition, these cells showed gain only in the neuron-derived neurotrophic factor (NF), while other neurotrophic factors such as glial line-derived NF and brain-derived NF presented normal copy numbers. Chromosomes 4, 8, 10, 11 and 15 displayed more than 1000 aberrational oligonucleotides, while chromosomes 3, 17, 18 and 19 displayed less than 20. The largest region of gain was located on chromosome 8 and its size was no less than 26.7 Mb (Chr8:8427841-35162415), while chromosome 4 had the longest region of single deletion, with a size of 15.1 Mb (Chr4:73265785-88374165).

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.18 no.12
• /
• pp.521-528
• /
• 2017

Excessive alcohol consumption is one of the leading causes of many neurological diseases, such as dementia and Alzheimer's disease, and many efforts are under way to solve them. Red ginseng is known to enhance neuronal survival, inhibit apoptosis, and promote nerve regeneration of nerve cells. This study examined whether Rg3-enriched Korean red ginseng extract (KRG) inhibits the apoptosis of PC12 cells caused by alcohol-induced neurotoxicity and how KRG regulates several factors related to the caspase mediated pathway. In this way, the cell survival rate and apoptosis rate of PC12 cells were measured using an EZ-Cytox cell viability assay kit and flow cytometry, respectively. The expression of the apoptosis-related proteins (Bcl-2, Bid, Bax and caspase-3) were analyzed by western blotting, and the significance of the measured results was confirmed using the ANOVA method. As a result, KRG increased the expression of Bcl-2; inhibited the expression of Bid, Bax, and caspase-3; and inhibited the apoptosis of alcohol-induced PC12 cells. These results mean that the KRG-induced increase in Bcl-2 expression and down-regulation of Bid and Bax expression down-regulate caspase-3 expression, which in turn inhibits the mitochondrial apoptotic pathways. This study suggests that KRG is worth developing as a neuroprotective agent candidate.

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

• YAKHAK HOEJI
• /
• v.44 no.1
• /
• pp.29-35
• /
• 2000

The methanol extracts were prepared from 46 oriental medicines currently used for stroke treatment, and the effects were assessed on the excitotoxic neuronal cell death induced by L-glutamate(Glu) in primary cultured rat cortical neurons. The extracts from Angelicae gigantis Radix, Manitis Squama, Acori graminei Rhizoma, Uncariae Ramulus et Uncus, Alpiniae Fructus, Paeoniae Radix, and Cnidii Rhizoma inhibited the Glu-induced neurotoxicity with the IC$_50$ values of 95.2, 218.6, 263.3, 295.1, 297.9, 310.1, and 446.7 $\mu$g/ m$\ell$, respectively. The extracts from Arisaematis Rhizoma, Loranthi Ramulus, Anemarrhenae Rhizoma, Carthami Flos, Clematidis Radix, Bambusae Concretio Silicea, and Angelicae koreanae Radix also exhibited significant inhibition of the toxicity. In contrast, the extracts from Aconiti Tuber Araliae cordatae Radix, Curcumae Rhizoma, Leonuri Herba, Polygalae Radix, Salviae Radix, and Siegesbeckiae Herba increased the Glu-induced toxicity at the concentrations of 500 and 1000 $\mu$g/m$\ell$. Rest of the extracts evaluated in the present study showed minor or negligible inhibition. liken together the oriental medicines including Angelicae gigantis Radix, Muitis Squama, Acori graminei Rhizoma, Uncariae Ramulus et Uncus, and Alpiniae Fructus appear to exert pharmacological effects through the inhibition of excitotoxic neuronal cell death. Further studies are in progress to characterize active principles in these extracts.

• YAKHAK HOEJI
• /
• v.46 no.6
• /
• pp.433-440
• /
• 2002

The protective efficacy of Rheum palmatum water extract on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism was studied in C57BL/6 mice. In order to demonstrate neuroprotective effect of R. palmatum extract, animals were administered intraperitoneally with the water extract (100 or 200 mg/kg/day) for 14 days, and MPTP (10 mg/kg/day) was injected subcutaneously into the mice for the first 6 consecutive days from the beginning 1 hr before R. palmatum extract treatment. All animals were measured the several neurobiochemical markers such as dopamine level and monoamine oxidase B (MAO-B) activity in various regions of brain. The treatment of mice with R. palmatum extract was confirmed recovery effect on MAO-B activity in the cerebellum and the cerebral cortex. R. palmatum extract was attenuated the MPTP-induced depletion of substantia nigra dopamine. The contents of MDA, a marker of lipid peroxidation, in brain tissues (cerebellum and cerebral cortex mitochondria) were decreased significantly by R. palmatum extract. These results suggest that R. palmatum water extract plays an effective role in attenuating MPTP-induced neurotoxicity in mice. This protective effect of R. palmatum might be estimated the result from the inhibitory activity on monoamine oxidase B and the enhancement of antioxidant activity.