백서 적혈구에서 glutathione이 paraquat 독성에 미치는 영향

김명철,박재윤,채기영,천영욱,박평심,차종희 朝鮮大學校 附設 醫學硏究所 1991 The Medical Journal of Chosun University Vol.16 No.2

The participation of superoxide in initiating tissue damage from administration of a xenobiotics is best illustrated by paraquat intoxication, in which it is known that one electron reduction of paraquat leads to the formation of radicals which react with molecular oxygen to give superoxide. In the present study, the effects of paraquat on the level of glutathione and activities of superoxide dismutase(SOD), catalase, glutathione peroxidase, glutathione reductase and glutathione stransferase were investigated in rat liver and erythrocytes. The contents of glutathione in liver and blood were sinificantly decreased by paraquat administration, but the activities of enzymes were unaltered. Incubation of the buffered aerobic mixture of erythrocyte in the presence of 5mM glucose, Paraquat and/or N-ethylmaleimide(NEM) resulted in the formation of lipid peroxide, the activities of various enzyme and the levels of glutathione were determined. The malondialdehyde(MDA) contents as a indicator of lipid peroxidation was decreased and the levels of total glutathione were not changed but the levels of oxidized glutathione(GSSG) were in creased in paraquat treated erythrocytes. The activites of ezyme were decreased in paraquat treated erythrocytes but in reduced glutathione(GSH) treated erythrocyte, the enzymes activities were less decreased by paraquat. These results suggest that paraquat toxicity was probably somewhat reduced by GSH, but paraquat-induced injury were not increased by GSH depletion in erythrocytes.

절식이 흰쥐의 간과 신장의 Thiobarbituric Acid - Reactive Substance량 및 항산화효소 활성도에 미치는 영향

박평심(Pyoung-Sim Park),고춘남(Choon-Nam Koh),박재윤(Jae-Yoon Park) 한국식품영양과학회 1999 한국식품영양과학회지 Vol.28 No.2

단기적인 완전절식에 의한 산화적 세포손상의 변화를 관찰하기 위해서 Sprague-Dawley 종 흰쥐를 물을 제외한 일체의 음식을 완전절식시킨 후 간 및 신장의 SOD, catalase, GSHPx 활성과 TBARS량을 측정한 결과, TBARS량은 신장에서 절식 후 감소되어 6일째에는 절식 전에 비하여 21% 감소하였고, 간에서도 절식 시작 후 4일 째에는 절식 전에 비하여 23% 감소되었다. SOD 활성도는 신장에서 절식 후 증가되어 5일째에는 절식 전에 비하여 31% 증가하였고, 간에서도 절식 후 증가되어 4일째에는 절식 전 효소 활성도에 비하여 20%가 증가되었다. Catalase 활성도는 신장에서 절식 후 6일째에는 절식 전에 비하여 27% 감소되었고, 간에서는 효소 활성도 변화가 없었으며, GSHPx 활성도는 신장과 간 모두에서 절식에 의한 효소 활성도 변화가 관찰되지 않았다. 이상의 실험 결과로서 완전절식에 의해서 TBARS량은 감소되고, 항산화효소 활성도의 변화는 효소의 종류에 따라서 서로 다른 양상을 나타내는 것을 알 수 있으며, 완전절식에 의한 TBARS량의 감소요인은 부분절식에 의한 요인과는 다른 것으로 추측된다. The effects of total dietary restriction(100% restriction of energy intake) on thiobarbituric acid-reactive substance(TBARS) contents and intracellular antioxidant enzymes activities in the liver and kidney of young male Sprague-Dawley rats were studied. The TBARS contents were reduced in both liver and kidney, up to 77% and 79% of the control rats, fed ad libitum, respectively at 7 days after dietary restriction. Superoxide dismutase(SOD) activities in the liver and kidney of rats were increased significantly by total dietary restriction. However, the activity of catalase in kidney was decreased 27% at 6 days after dietary restriction, but this enzyme activity did not change in liver. The changes of glutathione peroxidae(GSHPx) and catalase activities in the liver and kidney of rats with dietary restriction were not significant. These result suggested that dietary restriction reduce the free radical induced by tissue damage, as determined by TBARS content, in both the liver and kidney but the changes of activities of antioxidant enzymes may not be a contributory factor in reducing oxidative damage to tissue.

양파즙이 에탄올에 의한 백서의 지질과산화물 생성에 미치는 영향

박평심(Pyoung-Sim Park),이병래(Byoung-Re Lee),이명렬(Myung-Yul Lee) 한국식품영양과학회 1994 한국식품영양과학회지 Vol.23 No.5

양파즙이 에탄올에 의한 백서의 간손상에 미치는 영향을 알아보기 위하여 정상군, 양파즙 투여군, 에탄올투여군, 에탄올과 양파즙병합 투여군으로 나누어 3주, 6주간 사육하여 간장의 TBA반응성 산물량, glutathione 함량, 총 sulfhydryl 함량, 비단백질성 sulfhydryl량 및 SOD, catalase, GPX, xanthine oxidase, 혈청중의 AST, ALT 및 ALP 활성의 변화를 관찰하였다. 양파즙은 3주간 투여에서 에탄올에 의하여 증가된 간 TBA 반응성 산물량을 유의하게 감소시켰으며 (p<0.05), glutathione 함량은 3주, 6주에서 에탄올 투여군에 비하여 유의한 증가를 나다냈다(p<0.0l, p<0.05). 총 sulfhydryl group 함량은 3주간 양파즙 투여에서 에탄올 투여군에 비하여 유의성 있게 증가되었으며 정상군의 함량에 근접하였다. 그러나 양파즙이 유리기 손상에 대한 효소계 항산화물질로 알려진 SOD, catalase, GPX 및 xanthine oxidase에서는 에탄올 투여군에 비하여 약간의 변화는 있었으나 유의한 변화는 나타내지 않았다. 양파즙은 에탄올 투여군에 비하여 혈청중의 aminotransferase와 alkaline phosphatase활성도 저하시켰다. 이상의 결과로 미루어 양파즙의 흰쥐에서 에탄올투여로 증가된 간지질과 산화물생성에 대한 양파즙의 억제효과는 효소적 항산화작용 보다는 비효소적 항산화작용을 나타내는 glutathione 및 sulfhydryl group 함량이 증가되므로서 산화물에 대한 방어력이 증강되어 나타난 결과로 여겨지며, 또한 간손상에 대한 지표효소로 알려진 혈청 amlnotransferase 및 alkaline phosphatase 효소활성을 유의성있게 감소시켰음은 양파즙이 에탄올에 의한 간세포 손상에 대한 방지작용이 있는 것으로 사료된다. The effects of onion juice on ethanol-induced lipid peroxidation were studied in rats. The contents of thiobarbituric acid (TBA)-reactants increased significantly in liver of ethanol (4ml/㎏/day) administered-rats. The activities of serum alanine aminotransferase and alkaline phosphatase increased by ethanol administration compared with control group, but alterations of antioxidant enzymes activites in liver of ethanol administeredrats were not significant vs control group. The glutathione contents in liver decreased by ethanol, whereas the glutathione levels increased in ethanol and onion juice group compared with ethanol group. The contents of hepatic TBA-reactants and serum aminotransferase activity in ethanol group were reduced by onion juice administration. In these results, increased hepatic TBA-reactants of liver in ethanol group might be due to decreased glutathione contents in liver. Reduced glutathione (GSH) plays an important roles in the liver in several detoxification and the reduction of lipid peroxides. So the protective effects of onion juice on ethanol-induced increment of TBA-reactants may be due to the increament of glutathions content. The glutathione depletion by ethanol was an important factor of ethanol-induced cell damage, and the prevention of onion juice to the glutathione depletion reduced by ethanol may be an important factor on the protection from ethanol-induced lipid peroxidation in rats.

양파식이가 흰쥐에서 사염화탄소 독성에 미치는 영향

박평심(Pyoung-Sim Park),이병래(Byoung-Re Lee),이명렬(Myung-Yul Lee) 한국식품영양과학회 1991 한국식품영양과학회지 Vol.20 No.2

양파식이가 CCl₄독성에 미치는 영향을 알아보기 위하여 생양파, 삶은양파, 양파즙을 실험식이로 흰쥐를 4주간 사육하여 체중, 식이섭취량, 장기중량, 형청지질농도와 간 및 신장의 SOD, catalase활성도 및 지질과산화도의 변화를 관찰하였다. 체중, 식이섭취량 및 장기의 중량에 있어서 유의적인 변화는 없었으나 신장의 무게는 CCl₄투여에 의해 증가 되었으나 양파로 유의한 감소효과를 나타냈다(p<0.05). 혈청 콜레스테롤 농도는 CCl₄투여로 증가를 나타냈으나 양파로 유의한 감소를 나타냈는데 생양파와 양파즙을 투여한 군에서 우수한 효과를 나타냈다. 간 및 신장의 SOD 및 catalase활성도는 모두 CCl₄투여로 효소활성도가 증가되었으나 양파투여로 효소활성도가 억제되었는데 양파즙이 우수한 영향을 나타냈다. 간 및 신장의 지질과산화도는 CCl₄투여로 증가되었던 지질과산화물인 malondialdehyde양이 양파투여로 인하여 감소되었다.<br/> 이상의 결과로 미루어 양파는 흰쥐에서 CCl₄투여로 증가된 혈청중의 지질함량을 낮추고 간장 및 신장의 MDA, SOD 및 catalase활성의 변화를 둔화시키는 것으로 보아 CCl₄독성을 완화시키는 작용이 있는것으로 시료된다. This study designs to investigate effects of onion diet on carbon tetrachloride toxicity of rats. Experiments were performed with week's feeding, body weight, food intake, ratio of organ weight/body weight, serum lipid levels, superoxide dismutase and catalase activity and malondialdehyde(MDA) content in liver and kidney were determined. The contents of serum total cholesterol in each group were lower than those of control group(p<0.05), especially at onion juice treated group. Serum HDL-cholesterol level of CBB and CBJ groups was significantly lower than that of control group (p<0.05). Superoxide dismutase activities of liver and kidney were significantly increased by carbon tetrachloride treatment and decreased by onion feeding. MDA contents in liver and kidney of CCl₄ treated rats were significantly decreased by boiled and fresh onion fed group, compared with CCl₄ treated control group. This result suggested that onion diet has a protective effect on CCl₄ induced hepatotoxicity and nephrotoxicity of rat.

Copper - Phenanthroline복합체에 의해 유도되는 DNA손상에 대한 양파와 마늘의 억제효과

박평심(Pyoung-Sim Park),이명렬(Myung-Yul Lee) 한국식품영양과학회 1992 한국식품영양과학회지 Vol.21 No.4

양파와 마늘이 산화적 DNA 손상에 미치는 영향을 시험관내에서 Cu^(+2)와 phenanthroline에 의해 유리된 TBA 반응물을 측정하여 관찰한 결과 양파가 마늘보다 더 강한 TBA 반응물 억제효과를 나타냈으며, 양파의 효과는 시료를 가열하여도 변화가 적었다. 항산화효소인 SOD활성은 마늘에서, catalase와 glutathione peroxidase 활성도는 양파에서 더 높았고, -SH기는 마늘에서 더 많았다. Cu^(+2)와 phenanthroline에 의한 산화적 DNA 손상에 대해 SOD와 catalase는 영향이 적고, glutathione은 영향이 비교적 큰것으로 나타나 양파의 마늘보다 더 큰 DNA 손상 억제효과는 항산화 효소나, -SH기에 의한것이 아니며, 특히 양파에 열을 가해도 DNA 손상 억제 효과의 감소가 적은점으로 보아 비교적 고온에서 안정된 물질이 Cu^(+2)와 phenanthroline에 의한 DNA 손상 억제효과를 나타내는 것으로 사료된다. In the present study, the effects of onion and garlic on copper and 1,10-phenanthroline complex induced DNA degradation were investigated by the decreased level of thiobarbituric acid (TBA) reactive materials. Phenanthroline is specific for copper and the reaction releases TBA reactive material from DNA which can be measured by absorbance at 535㎚. The levels of TBA reactive materials were decreased by adding onion or garlic homogenate into reaction mixture but the onion had more strong potency and the effect of onion was not changed by boiling. Superoxide dismutase (SOD) and catalase have no inhibitory effects on copper induced DNA damage but reduced glutathione was more effective. The activities of antioxidant enzymes and the contents of sulfhydryl groups in onoin and garlic were also investigated. The activity of SOD was more higher in garlic, but catalase and glutathione peroxidase activities were higher in onion. The contents of sulfhydryl group in garlic was more abundant. This result suggested that inhibitory effects of onion on copper induced DNA damage were not by antioxidant enzymes such as SOD, catalase and glutathione peroxidase or sulfhydryl groups, but a substance which is more stable in high temperature.

Antimicrobial Activity of Mulberry Leaf against Mutans Streptococci and Periodontopathogens

Soon-Nang Park,Yun Kyong Lim,Eugene Cho,Eojin Jo,Pyoung-Sim Park,Joong-Ki Kook KOREAN ACADAMY OF ORAL BIOLOGY 2014 International Journal of Oral Biology Vol.39 No.4

This study investigated the antimicrobial activity of methanol extract of mulberry leaf against 16 strains of mutans streptococci and four species of periodontopathogens: Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. The antimicrobial activities of the crude extracts or silica gel chromatography fractions of methanol-extracted mulberry leaf were evaluated by determining minimal inhibitory concentrations using an established microdilution method. The cytotoxicity of the extracts of mulberry leaf on KB cells was tested by the methyl thiazolyl tetrazolium assay. Chromatography fraction 12 displayed the most potent antimicrobial activity against all 16 strains of mutans streptococci, P. gingivalis, and P. intermedia. No KB cell cytotoxicity was evident up to 128 μg/ml of fraction 12. The methanol extract had no antimicrobial activity against F. nucleatum and A. actinomycetemcomitans. These results suggest chromatography fraction 12 methanol extract of mulberry leaf could be useful in the development of oral hygiene products, such as dentifrice and oral hygiene solution, for the prevention of dental caries.

천연물의 심혈관질환에 대한 약리적 효과

임리진(Leejin Lim),박평심(Pyoung Sim Park),송희상(Heesang Song) 대한약학회 2015 약학회지 Vol.59 No.4

Cardiovascular disease is one of the leading cause of death in many developed countries as well as developing countries. Many evidences indicate that natural products have profound beneficial effects for cardioprotection. In addition to the crude extracts, an identified single compound may be used as a lead molecule for the therapeutic interests. In this review, we discuss promising natural products for cardiovascular diseases, their molecular targets, and their mechanisms, which may help the further direction of studies and applications of natural products for cardiovascular diseases.

사람 폐암 세포주에서 시스플라틴이나 독소루비신의 세포독성에 미치는 녹차 추출물의 영향

이병래(Byoung-Rai Lee),박재윤(Jae-Yoon Park),박평심(Pyoung-Sim Park) 한국식품영양과학회 2011 한국식품영양과학회지 Vol.40 No.5

항암 화학요법제의 항암작용을 증가시키거나, 부작용을 감소시켜 항암 치료를 효과적으로 할 수 있는 항암치료 보조제(modulator)에 대한 개발의 일환으로 녹차 추출물의 이용 가능성을 추정하기 위하여 사람 폐암 세포주인 A549 세포를 배양하여 시스플라틴과 독소루비신의 항암성에 미치는 녹차 추출물과 EGCG의 영향을 비교 관찰하였다. A549 세포에 독성을 나타나는 농도는 녹차 추출물 400 ㎍/mL, EGCG 300 ㎍/mL, 시스플라틴 10 ㎍/mL 및 독소루비신 8 ㎍/mL로, 녹차 추출물이 세포독성을 나타내는 농도는 시스플라틴이나 독소루비신에 비하면 낮았다. A549 세포에서 시스플라틴 10 ㎍/mL 이상의 농도에서 세포활성이 감소되었고, EGCG나 녹차 추출물 100 ㎍/mL를 첨가하면 시스플라틴 6 ㎍/mL 이상의 농도에서 세포활성이 감소되어 EGCG나 녹차 추출물 첨가로 시스플라틴의 세포독성이 증가되었다. A549 세포에서 독소루비신 8 ㎍/mL 이상의 농도에서 세포활성이 감소되었고, EGCG나 녹차 추출물 100 ㎍/mL를 첨가하면 독소루비신 4 ㎍/mL 이상의 농도에서 세포활성이 감소되어 EGCG나 녹차 추출물 첨가로 독소루비신의 세포독성이 증가되었다. A549 세포에서 녹차추출물 투여 후 p53 및 caspase-3에 대한 Western blot을 시행한 결과 p53및 caspase-3의 유전자 발현이 증가되었다. 이상의 실험결과 녹차추출물은 광범위 항암제 시스플라틴이나 독소루비신의 세포독성을 증강시키는 효과가 있고, 녹차추출물에 의한 p53이나 caspase-3 등과 같은 세포자살유도 단백질의 발현 증가는 녹차추출물에 의한 세포독성 증강효과와 연관이 있을 것으로 추측된다. 녹차추출물의 시스플라틴이나 독소루비신 세포독성 증강효과는 항암화학요법제의 용량을 늘리지 않고 항암력을 증대시킬 수 있기 때문에 항암화학요법 보조제로서 이용될 수 있는 가능성이 높은 것으로 생각되며, 이러한 효과를 규명하기 위한 연구가 필요할 것으로 사료된다. Tea extract (TE) has been shown to have anti-tumor properties in a wide variety of experimental systems. We evaluated green tea extract (GTE) as a biochemical modulator for the antitumor activity of cisplatin and doxorubicin in the treatment of human lung cancer A549 cells. Cells were grown in RPMI-1640 medium supplemented with 10% (v/v) heat-inactivated fetal bovine serum and two antibiotics (100 units/mL penicillin and 100 ㎍/mL streptomycin). Two types of TE, epigallocatechin galate (EGCG) and GTE, were used in this experiment. The cells were seeded at 1×10⁴ cells/well in the RPMI-1640 media with or without TE (100 ㎍/mL) and then treated with different concentrations of doxorubicin (0~14 ㎍/mL) or cisplatin (0~35 ㎍/mL). After incubation in 5% CO₂ at 37℃ for 24 hr, cell viability was determined with a MTT assay. We used a Western blot to detect the influence of EGCG and GTE on the expression of p53 and caspase-3 genes in the A549 cells. A549 cell viability decreased to 15% with a 10 ㎍/mL concentration of cisplatin, and to 21% with a 8 ㎍/mL concentration of doxorubicin, as measured with the MTT assay. However, pre-treatment of the cells with EGCG (100 ㎍/mL) or GTE (100 ㎍/mL) resulted in decreased cell viability with 6 ㎍/mL of cisplatin and 4 ㎍/mL of doxorubicin. There was no apparent change in cell viability between EGCG or GTE administration in cisplatin- or doxorubicin-induced cytotoxicity in A549 cells. The levels of p53 and caspase-3 in the A549 cells increased with both EGCG and GTE treatment. We found that GTE could potentially affect cisplatin- or doxorubicin-induced cytotoxicity of A549 cells, which may be useful in the chemotreatment of cancer.

카테킨과 퀘르세틴 병합 투여가 당뇨병 흰쥐의 간 당질 대사에 미치는 영향

이병래(Byoung Rai Lee),박평심(Pyoung Sim Park) 한국식품영양과학회 2022 한국식품영양과학회지 Vol.51 No.1

대장암(CT 26) 생쥐에서 녹차추출물 음용에 의한 시스플라틴 항암작용 증강효과

이병래(Byoung-Rai Lee),박평심(Pyoung-Sim Park) 한국식품영양과학회 2012 한국식품영양과학회지 Vol.41 No.8

Green tea intake is known to have preventive effects against cancer. In this study, we evaluated the tumor suppressive effects of dietary green tea extracts (GTE) as a modulator on cisplatin in an established colon cancer mouse model. The cisplatin-induced cytotoxicity was determined with cell viability of the mouse colon cancer cell line (CT26) in vitro. The influence of GTE on the anti-tumor activity of cisplatin was evaluated by measuring tumor size with digital calipers in mice bearing CT26 colon carcinomas. The CT26 cell viability decreased to 93% at a 20 μg/mL concentration of cisplatin. However, cell viability decreased to 15% with a combination of 20 μg/mL cisplatin and GTE (75 μg/mL). There were no apparent changes in cisplatin-induced cytotoxicity with GTE and epigallocathechin gallate (EGCG) treatments. Tumor size decreased in dietary GTE combining intra-peritoneal cisplatin-injected tumors bearing mice compared with cisplatin or GTE alone administered to tumor-bearing mice. These experiments showed that dietary GTE has a potentiating effect on the cisplatin anti-tumor activity of an established mice colon cancer model. Therefore, the GTE may be a candidate for modulators in anticancer treatments with cisplatin.