• 한국자원식물학회지
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• 제30권2호
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• pp.125-132
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• 2017

BPA는 내분비교란물질로 널리 알려져 있다. BPA를 세포와 실험동물에 처리하여 독성을 유도하고 이를 인삼 추출물들이 BPA로 유도된 독성에 어떠한 영향을 미칠 것인지 살펴보았다. WGE, DGE, RGE에 대한 항산화능을 DPPH 분석법으로 측정하였다. DGE 및 RGE는 DPPH 소거 항산화 활성을 증가시켰다. 간암세포주 HepG2에 BPA 처리하여 세포독성을 유도하고, 이를 인삼추출물에 의해 세포생존이 증가되는지 MTT법으로 측정하였다. BPA $200{\mu}M$ 처리하여 유도된 세포독성에 DGE 및 RGE는 세포 생존 능력을 증가시켰다. 실험동물에 BPA를 처리하여 독성을 유도하고 이를 인삼추출물들이 방어하는지 살펴보았다. 혈청에서 간 손상 생화학적 마커인 AST와 ALT가 RGE 투여군에서 증가했다. 또한, 손상된 간세포 재생및 증식이 RGE 투여군에서 현저하게 증가하였다. 또한, RGE 주변 영역 및 간 미세 구조의 중심 정맥의 문맥에서 간 섬유화를 억제하였다. 이상의 결과를 종합하면 RGE가 간 세포주에서 BPA로 유도된 세포독성을 유의적으로 저해하였으며, 동물실험을 통하여 BPA에 의해 손상된 간에서 RGE가 간의 보호와 간 조직 재생이 발생하는 것을 확인하였다. 이 결과는 RGE가 외부에서 유입된 화학물질에 대한 간 손상 개선제로 사용될 수 있음을 보여준다. 그러므로, RGE는환경독성 물질로 인한 질환치료약물에 대한 잠재적인 후보가 될 수 있을 것이라 사료된다.

• 대한약리학회지
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• 제27권2호
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• pp.197-205
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• 1991

Adriamycin (Doxorubicin HCl)의 혈관밖 유출에 따른 조직의 손상, 특히 피부괴양 및 괴사 기전을 규명하기 위한 연구의 일환으로 흰쥐 피부세포를 이용한 in vitro 실험에서 adriamycin에 의한 산소라디칼 생성 및 그와 관련된 세포독성 기전으로 지질과산화를 검토하였다. Adriamycin은 흰쥐 태자 피부의 배양세포에서 lactic dehydrogenase(LDH) 유리를 용량 및 시간 의존적으로 증가 시켰으며, NADPH 및 NADH 첨가 조건에서 $superoxide\;anion(O^-\;_2{\cdot})$ 생성을 현저히 증가시켰다. Adriamycin은 지질과산화 반응의 척도인 malondialdehyde(MDA) 생성을 역시 NADPH, NADH 존재하에서 용량의존적으로 증가시켰고, 산소라디칼 제거물질들인 superoxide dismutase (SOD), catalase 및 thiourea와 항산화물질인 butylated hydroxytoluene(BHT), ${\alpha}-tocopherol$은 MDA 생성증가를 현저히 억제하였다. 1, 3,-bis(2-chloroethyl)-1-nitrosourea(BCNU)를 처리하여 산화성 공격에 대한 방어기전의 하나인 glutahione 체계를 억제할 경우 adriamycin에 의한 MDA 생성은 더욱 현저히 증가하였고, 이는 역시 항산화 물질들에 의하여 억제되었다. 이상의 연구성적에서 adriamycin은 산소라디칼 생성의 증가와 그에 따른 지질과산화를 촉진하므로서 피부세포에 손상을 줄 것으로 사료되었다.

• 생명과학회지
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• 제31권2호
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• pp.223-228
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• 2021

Cyclophosphamide (CP)는 면역 억제제 뿐만 아니라 암 및 림프종 등의 치료에 널리 사용된다. CP는 DNA 알킬화제로서, 간세포에서 대사되어 4-hydrocyclophosphamide (4H-CYP)와 aldophosphamide로 분리된다. Ulmus macrocarpa Hance는 부종, 유방염, 종양 및 기타 염증성 질환에 사용되어 왔다. 이 연구의 목적은 CP의 부작용에 대하여 U. macrocarpa Hance 열수 추출물이 조직학적 수준에서 CP의 부작용에 대한 간과 신장의 보호 기능과 U. macrocarpa Hance 자체의 잠재적 독성 영향을 조사하고자 하였다. 마우스 모델을 사용하여 헤마톡실린 및 에오신(H&E) 염색과 DAPI 염색으로 간과 신장을 조직학적으로 분석하였다. CP 처리한 마우스에서 간세포의 형태는 글리코겐 축적을 나타내지 않았고, 세포 밀도도 감소하였다. 그러나 UMWE+CP 처리군에서는 간세포의 형태와 세포 밀도는 정상 간세포 패턴과 유사하였다. 또한, UMWE으로만 처리한 마우스에서도 간세포의 형태와 세포 밀도는 정상 간세포와 유사했다. 신장의 경우에는 정상 마우스와 비교했을 때 H&E 염색으로는 CP 또는 UMWE 처리된 마우스의 신장에서 명백한 차이를 나타내지 않았다. 즉, U. macrocarpa Hance의 열수추출물은 간과 신장에 아무런 영향을 유발하지 않으면서 CP가 유발한 독성을 감소시키는것으로 요약된다. 따라서 U. macrocarpa Hance는 제약 산업에 사용될 수 있는 가능성을 나타내었다.

• 동의생리병리학회지
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• 제21권5호
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• pp.1118-1126
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• 2007

The purpose of this study was to examine the anti allergic effect in vivo and in vitro, and to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated anti DNP IgE-mediated passive cutaneous anaphylaxis in rodents and compound 48/80-induced active systemic anaphylatic shock in mice after oral administration with BGT of 0.4 g/kg and 0.8 g/kg for 8 days, and also examined MTT assay, ${\beta}-hexosaminidase$ activity, IL-4 and $TNF-{\alpha}$ from RBL-2H3 and $TNF-{\alpha}$ from Raw264.7 after pre-treatment with BGT of 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml and 2 mg/ml. To ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg /p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. BGT inhibited passive cutaneous anaphylaxis and active systemic anaphylatic shock by oral administration. All the concentrations of BGT from 0.25 to 2 mg/ml didn't have an effect on cell viability and cytotoxicity. In RBL-2H3, ${\beta}-hexosaminidase$ release, IL-4 and $TNF-{\alpha}$, and in Raw264.7, $TNF-{\alpha}$ were significantly reduced by treated all concentrations of BGT. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.

• 동의생리병리학회지
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• 제26권6호
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• pp.869-873
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• 2012

Balance between bone-forming osteoblasts and bone-resorbing osteoclasts is important in bone homeostasis. Unusual balance between bone-forming osteoblasts and bone-resorbing osteoclasts leads to bone diseases, such as osteoporosis. Saururus chinensis has been widely used in oriental medicine. Saururus chinensis has been known that has antioxidant and anticancer effect. But, the effect of Saururus chinensis in osteoclast differentation remains unknown. We examined the effect of Saururus chinensis in receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. From the results of our study, we found that saururus chinensis clearly inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMM) in a dose dependent manner without toxicity. Saururus chinensis inhibited the phosphorylation of JNK, P38, AKT, and ERK induced by RANKL. The mRNA expression of NFATc1, TRAP, and OSCAR induced by RANKL was inhibited by Saururus chinensis treatment. Moreover Saururus chinensis suppressed the protein expression of c-Fos and NFATc1 in BMMs treated with RANKL. These results suggest that Saururus chinensis may be a useful drug in the treatment of bone-related disease.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7003-7006
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• 2015

Background: Nanoparticles of gold and silver are offering revolutionary changes in the field of cancer therapy. N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and are being investigated as potential chemotherapeutic agents. The purpose of this study was to examine the cytotoxicity and possible mechanisms of action of two types of newly synthesized nanofiber composites containing BIAN N-heterocyclic gold carbene complexes in two types of human cancer cells, namely breast cancer (MCF7) and liver cancer (HepG2) cells and also in normal human embryonic kidney cells (HEK 293). Materials and Methods: Cytotoxicity was assessed by MTT cell viability assay and oxidative stress by checking the total glutathione level. Results: Both compounds affected the cell survival of the tested cell lines at very low concentrations (IC50 values in the micro molar range) as compared to a well-known anti-cancer drug, 5 fluorouracil. A 60-80% depletion in total glutathione level was detected in treated cells. Conclusions: Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates.

• Journal of Periodontal and Implant Science
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• 제24권2호
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• pp.397-405
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• 1994

Minocline Strip(MS), a local drug delivery developed as a controlling means for microoragnisms in gingival wound and periodontitis, was implanted in the gingiva of experimental animals. The toxic effects and biodegradation of MS were studied in respect to pathological changes induced in gingival tissue. The experimental animals treated with MS had not showed significant difference in symptom, body weights, feed and water intake, and blood analysis throughout 150 days of experimental period, but revealed significantly increased values of total WBC counts and AST (SGOT) on the 7th day, compared with controls. The treated animals revealed petechial hemorrhage and severe edema accompanying degeneration and necrosis of damaged muscle fibers around the surgical wound, but no local inflammatory reaction and concerned lesions were found. The implanted MS became encapsulated by thin connective tissue, and its size and color diminished gradually according to the experimental term. The MS-like material appeared in the nearby lymphatics on the 110th day. The implated MS remained as fine granular particles or disappeared on the 130th day, and the decrease of its volume and density were variable depending on each individual. These results indicate that long-term implantation of MS may not produce inflammation or toxic effects, and eventually lead to complete biodegradation.

• IMMUNE NETWORK
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• 제12권3호
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• pp.126-128
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• 2012

We report on a case of severe hepatotoxicity in a 52-year-old male with multiple myeloma (MM) who had received bortezomib therapy. At patient presentation, liver enzymes were normal, but started to markedly increase 3 days after the patient's second dose of bortezomib was administered, when free kappa light chains were noticeably reduced in the serum. After discontinuation of bortezomib, liver enzymes recovered gradually to baseline. Then, the patient was started on a thalidomide-containing regimen, which he was able to tolerate well. The patient achieved complete remission prior to autologous stem cell transplantation (ASCT). The patient underwent ASCT without occurrence of further liver toxicity.

• 대한의생명과학회지
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• 제13권4호
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• pp.273-278
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• 2007

Stem cells have been the subject of increasing scientific interest because of their utility in numerous biomedical applications. Stem cells are capable of renewing themselves; that is, they can be continuously cultured in an undifferentiated state, giving rise to more specialized cells of the human body. Therefore, stem cells are an important new tools for developing unique, in vitro model systems to test drugs and chemicals and a potential to predict or anticipate toxicity in humans. In the present study, in vitro cultured F3 immortalized human neural stem cell line and in vivo adult Sprague Dawley rats was used to evaluate the cytotoxicity of anticancer drug paclitaxel. In vitro apoptotic activity of paclitaxel was evaluated in F3 cell line by a MTT assay and DAPI test. The cell death was induced with the treatment of 20 nM paclitaxel and chromatin degradation was detected by DAPI staining, which was analyzed by fluorescent microscope. In vivo studies, we also observed nestin immunoreactivity on subventricular zone, which is stem cell rich region in the adult brain of the SD rat. Immunofluorescent staining result shows that pixel intensities of nestin were decreased in a dose dependent manner. These results suggest that paclitaxel is able to induce cytotoxic activity both in F3 neural stem cell line and neural stem cell in SD rat brain.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.268-274
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• 2005

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.