• Bulletin of the Korean Chemical Society
• /
• v.30 no.10
• /
• pp.2309-2317
• /
• 2009

Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though $N^7$-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.6
• /
• pp.1500-1508
• /
• 2003

This study was performed to clarify the neurotoxic mechanism of nerve cells damage by brain ischemia. The cytotoxic effect of ischemia was determined by XTT assay, NR assay, superoxide dismutase(SOD) activity, amount of malondialdehyde(MDA), lactate dehydrogenase(LDH) activity, protein synthesis and tumor necrosis factor(TNF)-α activities after cerebral neurons derived from mouse were exposed to ischemia for 1∼30 minutes. In addition, the protective effect of extract of Daejo-whan(DJW) on ischemia-induced neurotoxicity was examined in these cultures. 1. Ischemia decreased cell number and viability by XTT assay or NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO₂ for 1∼20 minutes in these cultures. 2. Ischemia decreased SOD and protein syntheses, but it increased amount of MDA and, LDH and TNF-α activities in these cultures. 3. In the neuroprotective effect of DJW extracts on cerebral neurons damaged by ischemia, DJW extracts increased SOD activity and protein synthesis. While, it decreased amount of MDA and, LDH and TNF-α activities after cerebral neurons preincubated with herb extracts. It suggests that brain ischemia has neurotoxicity on cultured mouse cerebral neurons, and the herb extract such as DJW was very effective in blocking the neurotoxicity induced by ischemia in cultured mouse cerebral neurons.

• The Journal of Korean Medicine
• /
• v.30 no.4
• /
• pp.13-27
• /
• 2009

Objectives: Trans-cinnamaldehyde (TCA) is the main component of Cinnamomi Ramulus and it has been reported that TCA inhibits inflammatory responses in various cell types. Inflammation-mediated neurological disorders induce the activation of macrophages such as microglia in brain, and these activated macrophages release various inflammation-related molecules, which can be neurotoxic if overproduced. In this study, we evaluated gene expression profiles using gene chip microarrays in lipopolysaccharide (LPS)-stimulated BV-2 cells to investigate the antiinflammatory effect of TCA on inflammatory responses in brain microglia. Methods: A negative control group was cultured in normal medium and a positive control group was stimulated with $1{\mu}g/ml$ in the absence of TCA. TCA group was pretreated with $10{\mu}g/ml$ before $1{\mu}g/ml$ LPS stimulation. The oligonucleotide microarray analysis was performed to obtain the expression profiles of 28,853 genes using gene chip mouse gene 1.0 ST array in this study. Results: In positive control group, 1522 probe sets were up-regulated in the condition of the cutoff value of 1.5-fold change and 341 genes with Unigene ID were retrieved. In TCA group, 590 probe sets were down-regulated from among 1522 probe sets and 33 genes with Unigene ID were retrieved, which included 6 inflammation-related genes. We found out that Id3 gene is associated with transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway and Klra8 gene is related to natural killer cell-mediated cytotoxicity pathway. Conclusions: The results mean that TCA inhibits inflammatory responses through down-regulating the expressions of inflammation-related genes in LPS-stimulated BV-2 cells.

• Biomolecules & Therapeutics
• /
• v.17 no.1
• /
• pp.47-56
• /
• 2009

Schizandra chinensis (S. chinensis) exhibits a harmless, 'adaptogen-type' effect leading to improvements in mental performance and learning efficacy in brain. Activated microglia contributes to neuronal injury by releasing neurotoxic products, which make it important to regulate microglial activation to prevent further cytological as well as functional brain damage. However, the effect of S. chinensis on microglial activation has not been examined yet. We have investigated the effects of four compounds (Gomisin A, Gomisin N, Schizandrin and Schizandrol A) from S. chinensis on lipopolysaccharide (LPS)-induced microglial activation. In this study, BV2 microglial cells were activated with LPS and the microglial activation was assessed by up-regulation of activation markers such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinase-9 (MMP-9). The results showed that all four compounds significantly reduced the intracellular level of ROS, the release of NO and MMP-9 as well as LPS-induced phosphorylation of ERK1/2. These results strongly suggested that S. chinensis may be useful to modulate inflammation-mediated brain damage by regulating microglial activation.

• Journal of Environmental Health Sciences
• /
• v.37 no.2
• /
• pp.102-112
• /
• 2011

Objectives: The purpose of this study is to analyze the effects of chronic exposure by welders to manganese (Mn) through an analysis of the degree of brain activity in different activities such as cognition and motor activities using the neuroimaging technique of functional magnetic resonance imaging (fMRI). The neurotoxic effect that Mn has on the brain was examined as well as changes in the neuro-network in motor areas, and the usefulness of fMRI was evaluated as a tool to determine changes in brain function from occupational exposure to Mn. Methods: A survey was carried out from July 2010 to October 2010 targeting by means of a questionnaire 160 workers from the shipbuilding and other manufacturing industries. Among them, 14 welders with more than ten years of job-related exposure to Mn were recruited on a voluntary basis as an exposure group, and 13 workers from other manufacturing industries with corresponding gender and age were recruited as a control group. A questionnaire survey, a blood test, and an fMRI test were carried out with the study group as target. Results: Of 27 fMRI targets, blood Mn concentration of the exposure group was significantly higher than that of the control group (p<0.001), and Pallidal Index (PI) of the welder group was also significantly higher than that of the control group (p<0.001). As a result of the survey, the score of the exposure group in self-awareness of abnormal nerve symptoms and abnormal musculoskeletal symptoms was higher than those of the control group, and there was a significant difference between the two groups (p<0.05, respectively). In the correlation between PI and the results of blood tests, the correlation coefficient with blood Mn concentration was 0.893, revealing a significant amount of correlation (p<0.001). As for brain activity area within the control group, the right and the left areas of the superior frontal cortex showed significant activity, and the right area of superior parietal cortex, the left area of occipital cortex and cerebellum showed significant activity. Unlike the control group, the exposure group showed significant activity selectively on the right area of premotor cortex, at the center of supplementary motor area, and on the left side of superior temporal cortex. In the comparison of brain activity areas between the two groups, the exposure group showed a significantly higher activation state than did the control group in such areas as the right and the left superior parietal cortex, superior temporal cortex, and cerebellum including superior frontal cortex and the right area of premotor cortex. However, in nowhere did the control group show a more activated area than did the exposure group. Conclusions: Chronic exposure to Mn increased brain activity during implementation of hand motor tasks. In an identical task, activation increased in the premotor cortex, superior temporal cortex, and supplementary motor area. It was also discovered that brain activity increase in the frontal area and occipital area was more pronounced in the exposure group than in the control group. This result suggests that chronic exposure to Mn in the work environment affects brain activation neuro-networks.

• Journal of Life Science
• /
• v.19 no.8
• /
• pp.1152-1158
• /
• 2009

For the toxicological pathologic study of amanita muscaria, we have investigated single and repeated dose toxicity in Sprague-Dawley (SD) rats. Single dose toxicity study was identified as catalepsy, incline and tail pinch methods (control 0 mg/kg, low 3.3 mg/kg, middle 16.5 mg/kg, high 33.0 mg/kg). Repeated dose toxicity study was carried out in blood tests, serum tests and histopathological methods. Neurotoxicity - muscle paralysis, and convulsion and loss of movement - was observed at 33.0 mg/kg group in the single dose toxicity study. Dysfunction of liver and kidney were shown in the repeated oral administration of the amanita muscaria at 3${\sim}$4 weeks. Serum chemistry results revealed a marked increase of LDH [Lactate Dehydrogenase (3181.5 IU/L; normal 230-460 IU/l)], ALT [Alanine transaminase (124.0 IU/l; normal <40 IU/l)] but the kidney was normal. Histopathological results show interstitial edema and tubular epithelial necrosis in the kidney. These results suggest that amanita muscaria has a neurotoxic effect and causes dysfunction of liver and kidney in the SD rat.