• Bulletin of the Korean Chemical Society
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• 제30권10호
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• pp.2309-2317
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• 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.

• 동의생리병리학회지
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• 제17권6호
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• pp.1500-1508
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• 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.

• 대한한의학회지
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• 제30권4호
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• pp.13-27
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• 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
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• 제17권1호
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• pp.47-56
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• 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.

• 한국환경보건학회지
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• 제37권2호
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• pp.102-112
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• 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.

• 생명과학회지
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• 제19권8호
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• pp.1152-1158
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• 2009

본 연구는 우리나라에 분포하는 광대버섯인 amanita muscaria로 단회투여독성시험과 반복투여독성시험을 하였을 때 SD 랫드의 독성병리학적 변화를 알아보고자 수행하였다. 단회투여독성시험은 강경증, 경사판법, 정압자극법을 이용하여 측정하였다. 강경증은 33 mg/kg의 농도에서 투여 2${\sim}$3 시간 후 강경증 시간이 감소하였다. 경사판법의 경우 33 mg/kg의 농도에서 투여 2시간 후 대조군과 비교하였을 때 낮은 경사 각도에서도 쉽게 미끄러졌으며, 앞다리 보다는 뒷다리 쪽에서의 움직임 감소를 보였다. 정압자극법의 경우 대조군, 저용량군, 중간용량군에서 SD 랫드가 자극을 인지하는 시간이 1${\sim}$2초 정도로 짧고 매우 공격적인 반응을 보였지만, 고용량군에서는 자극인지 시간이 대략 3${\sim}$5초로 증가하였으며, 대부분 공격적인 반응을 보이지 않는 것이 관찰되었다. 강경증, 경사판법, 정압자극법 모두 투여 4시간 후 대조군과 비슷한 수치로 회복되었으며 이것으로 보아 섭취 4시간 전후에는 amanita muscaria의 독성이 현저히 감소하는 것으로 확인되었다. 반복투여독성시험은 혈액, 혈청분석, 조직 병리학적 검사를 실시하였다. 혈청 분석에서 투여군과 대조군을 비교하였을 때 BUN과 creatinine의 변화는 없었지만 ALT와 LDH는 투여군에서 증가하였다. 이러한 결과를 바탕으로 표적장기인 간과 신장의 손상을 의심하였고 조직 병리학적 검사를 통해 간과 신장의 손상을 확인할 수 있었다.