• 한국식품영양과학회지
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• 제37권3호
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• pp.294-301
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• 2008

본 연구는 삼백초(aururus chinensis), 포공영(Taraxacum platycarpum), 유근피(Ulmus macrocarpa), 감초(Glycyrrhiza glabra), 흑두(Rhynchosia nulubilis)로부터 제조된 생약재 추출 혼합물이 dioxin 중 중독성이 가장 강하다고 알려진 2,3,7,8-tetrachlorodinenzo-p-dioxin(TCDD)에 의한 산화적 스트레스에 미치는 효과를 실험하였다. 정상적인 간세포주를 TCDD에 노출시킨 후 OHEM을 처리한 결과, TCDD에 의한 세포독성을 감소시켰으며, 간세포주로부터 생성된 lactate dehydrogenase, nitric oxide, cytochrome p450의 생성량 측정 결과로 OHEM이 TCDD로 유발된 간 독성을 해독할 수 있는 것으로 나타났다. 그리고 rat을 이용한 TCDD 급성독성 유발 실험에서는 TCDD 투여에 의해 증가된 AST, ALT, ALP, LDH 및 동맥경화지수가 OHEM의 투여에 의해 유의성 있게 감소하였으며 OHEM의 사전투여에 의한 방어효과가 높은 것으로 측정되었다(p<0.05). 또한 OHEM의 투여가 TCDD에 의해 손상된 간세포 조직의 풍선 병변과 공포화를 감소시켰고, 소장 세포의 조직에서는 융모 조직의 부종을 현저하게 감소시켰다.

• Journal of Microbiology and Biotechnology
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• 제20권11호
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• pp.1563-1570
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• 2010

To construct a highly sensitive detection system for endocrine disruptors (EDs), we have compared the activity of promoters with the n-alkane-inducible cytochrome P450 gene (ALK1), isocitrate lyase gene (ICL1), ribosomal protein S7 gene (RPS7), and the translation elongation factor-1${\alpha}$ gene (TEF1) for the heterologous gene in Yarrowia lipolytica. The promoters were introduced into the upstream of the lacZ or hERa reporter genes, respectively, and the activity was evaluated by ${\beta}$-galactosidase assay for lacZ and Western blot analysis for hER${\alpha}$. The expression analysis revealed that the ALK1 and ICL1 promoters were induced by n-decane and by EtOH, respectively. The constitutive promoter of RPS7 and TEF1 showed mostly a high level of expression in the presence of glucose and glycerol, respectively. In particular, the TEF1 promoter showed the highest ${\beta}$-galactosidase activity and a significant signal by Western blotting with the anti-estrogen receptor, compared with the other promoters. Moreover, the detection system was constructed with promoters linked to the upstream of the expression vector for the hER${\alpha}$ gene transformed into the Y. lipolytica with a chromosome-integrated lacZ reporter gene under the control of estrogen response elements (EREs). It was indicated that a combination of pTEF1p-hER${\alpha}$ and CXAU1-2XERE was the most effective system for the $E_2$-dependent induction of the ${\beta}$-galactosidase activity. This system showed the highest ${\beta}$-galactosidase activity at $10^{-6}\;M\;E_2$, and the activity could be detected at even the concentration of $10^{-10}\;M\;E_2$. As a result, we have constructed a strongly sensitive detection system with Y. lipolitica to evaluate recognized/suspected ED chemicals, such as natural/synthetic hormones, pesticides, and commercial chemicals. The results demonstrate the utility, sensitivity, and reproducibility of the system for identifying and characterizing environmental estrogens.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.83-91
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• 1999

Angiotensin II (ANG II) has a biphasic effect on $Na^+$ transport in proximal tubule: low doses of ANG II increase the $Na^+$ transport, whereas high doses of ANG II inhibit it. However, the mechanisms of high dose ANG II-induced inhibition on $Na^+$ uptake are poorly understood. Thus the aim of the present study was to investigate signal transduction pathways involved in the ANG II-induced inhibition of $Na^+$ uptake in the primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined serum-free medium. ANG II $(10^{-9}\;M)-induced$ inhibition of $Na^+$ uptake was blocked by losartan $(10^{-8}\;M,\;AT_1\;antagonist),$ but not by PD123319 $(10^{-8}\;M,\;AT_2\;antagonist)$ (P<0.05). ANG II-induced inhibition of $Na^+$ uptake was also completely abolished by neomycin $(10^{-4}\;M,$ PLC inhibitor), W-7 $(10^{-4}\;M,$ calmodulin antagonist), and $AACOCF_3\;(10^{-6}\;M,\;PLA_2\;inhibitor)$ (P<0.05). ANG II significantly increased $[^3H]arachidonic$ acid (AA) release compared to control. The ANG II-induced $[^3H]AA$ release was blocked by losartan, $AACOCF_3,$ neomycin, and W-7, but not by PD123319. ANG II-induced $[^3H]AA$ release in the presence of extracellular $Ca^{2+}$ was greater than in $Ca^{2+}-free$ medium, and it was partially blocked by TMB-8 $(10^{-4}\;M,$ intracelluar $Ca^{2+}$ mobilization blocker). However, in the absence of extracellular $Ca^{2+},$ it was completely blocked by TMB-8. In addition, econazole $(10^{-6}\;M,$ cytochrome P-450 monooxygenase inhibitor) and indomethacin $(10^{-6}\;M,$ cyclooxygenase inhibitor) blocked ANG II-induced inhibition of $Na^+$ uptake, but NGDA $(10^{-6}\;M,$ lipoxygenase inhibitor) did not affect it. In conclusion, $PLA_2-mediated$ AA release is involved in ANG II-induced inhibition of $Na^+$ uptake and is modulated by $[Ca^{2+}]_i$ in the PTCs.

• 한국발생생물학회지:발생과생식
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• 제10권3호
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• pp.197-202
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• 2006

어류의 체내에서 성분화를 유도하는 물질이 성스테로이드호르몬(sex steroid hormone)이라는 사실이 잘 밝혀져 있으며, 성스테로이드 생합성 효소의 하나인 aromatase도 성분화에 직접적인 역할을 하는 것으로 알려져 있다. 본 연구에서는 유전적으로 암컷인 틸라피아 자어(larvae) 집단을 aromatase 저해제(aromatase inhibitor, AI)인 Fadrozole로 침지 처리하여 초기 발생단계 중 어느 시기에 aromatase가 성분화 유도 작용을 하는 지를 조사하였다. Fadrozole 처리 유무 및 처리 농도의 차이는 부화 자어의 생존율에 유의한 차이를 유발하지 않았다. 하지만, 부화후 11일과 13일째에 고농도의 Fadrozole로 처리한 실험군의 자어는 유전적인 성이 암컷임에도 불구하고 유의하게 높은 비율의 자어가 수컷으로 분화하였다. 이 결과는 틸라피아 부화 자어가 스테로이드 생합성 효소의 저해에 아주 민감하게 반응하며, 이 종에서 aromatase의 주된 작용시기가 예상보다 훨씬 빠른 부화 후 11일 전후라는 사실을 보여준다. 또한 이상의 결과는 단 3시간의 AI 침지 처리가 유전적으로 설정되어 있는 성과 반대방향으로의 성분화를 유도하기에 충분할 정도로 강력함을 의미한다.

• 대한약리학회지
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• 제17권1호
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• pp.17-25
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• 1981

No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

• The Korean Journal of Physiology and Pharmacology
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• 제17권6호
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• pp.479-484
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• 2013

Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of $CYP3A4^*1B$ (rs2740574) and $CYP3A5^*3C$ (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of $CYP3A4^*18$ (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3925-3929
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• 2013

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.781-784
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• 2016

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.

• Journal of Microbiology and Biotechnology
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• 제34권3호
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• pp.606-621
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• 2024

This study evaluated the hepatoprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced liver injury mice. As a result of amino acids in FPB, 18 types of amino acids including essential amino acids were identified. In the results of in vitro tests, FPB increased alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. In addition, FPB treatment increased cell viability on ethanol- and H₂O₂-induced HepG2 cells. FPB ameliorated serum biomarkers related to hepatoxicity including glutamic oxaloacetic transaminase, glutamine pyruvic transaminase, total bilirubin, and lactate dehydrogenase and lipid metabolism including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Also, FPB controlled ethanol metabolism enzymes by regulating the protein expression levels of ADH, ALDH, and cytochrome P450 2E1 in liver tissue. FPB protected hepatic oxidative stress by improving malondialdehyde content, reduced glutathione, and superoxide dismutase levels. In addition, FPB reversed mitochondrial dysfunction by regulating reactive oxygen species production, mitochondrial membrane potential, and ATP levels. FPB protected ethanol-induced apoptosis, fatty liver, and hepatic inflammation through p-AMP-activated protein kinase and TLR-4/NF-κB signaling pathways. Furthermore, FPB prevented hepatic fibrosis by decreasing TGF-β1/Smad pathway. In summary, these results suggest that FPB might be a potential prophylactic agent for the treatment of alcoholic liver disease via preventing liver injury such as fatty liver, hepatic inflammation due to chronic ethanol-induced oxidative stress.

• Tuberculosis and Respiratory Diseases
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• 제47권6호
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• pp.768-774
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• 1999

연구배경: 리팜핀(rifampin)은 간의 시토크폼 P-450 효소를 유도하여 이 효소에 의해서 대사되는 와파린(warfarin)의 항응고 효과를 감소시킨다. 이와 같은 리팜핀과 와파린의 약제 상호작용에 대해서 건강한 지원자가 아닌 환자를 대상으로 아래의 문제를 해결하고자 본 연구를 수행하였다. 첫째 와파린을 투여하는 환자에게 리팜핀을 추가할 경우 리팜핀 투여 전, 중, 후에 항응고 효과를 적절히 유지하기 위한 와파린 용량, 둘째 리팜핀 추가 후 적절한 와파린 증량 방법(시간 계획), 셋째 와파린과 리팜핀을 함께 투여하는 경우 합병증등을 살펴 보았다. 방 법: 1995년 1월부터 1999년 8월까지 부천 세종병원에 입원한 환자 중 와파린과 리팜핀을 동시에 투여한 환자를 찾아서 질병 기록을 후향적으로 확인하였다. 리팜핀 투여 전, 중, 후의 와파린 필요량을 '적절한 항응고' 상태를 유지한 환자를 대상으로 조사하였다. 그리고, 리팜핀 추가 시 와파린 증량 방법(시간 계획)을 리팜핀 투여 후 prothrombin time 이 INR 1.1이하로 떨어지는데 걸리는 시간을 측정하여 간접적으로 평가하였다. 마지막으로 리팜핀과 와파린 동시 투여시 합병증을 조사하였다. 결 과: 라팜핀과 와파린을 동시에 투여한 환자는 모두 12명이었고 이 중 리팜핀 투여 기간 중에 '적절한 항응고' 상태를 유지한 환자는 6명이었다. 이 6명환자의 와파린 용량은 리팜핀 투여 중에 증가하여(p<0.05) 리팜핀 투여 전과 비교하여 $2.4{\pm}0.6$(평균${\pm}$표준편차) 배이었다. 그라고, 리팜핀을 중지한 후의 와파린 용량은 다시 감소하여 거의 리팜핀 사용 전의 용량으로 돌아갔다. 리팜핀 투여 후 prothrombin time이 INR 1.1이하로 떨어지는데 걸리는 시간은 $5.8{\pm}2.9$ (평균$\pm$표준편차) 일이었다. 2명이 리팜핀과 와파린 동시 투약과 관련되어 합병증이 발생하였다. 한 명은 낮은 항응고 상태 때문에 뇌색전증이 발생하였고, 다른 한명은 높은 항응고 상태 때문에 뇌출혈이 발생하여 사망하였다. 결 론: 와파린과 리팜핀을 동시에 투약하는 경우, 적절한 항응고 효과를 유지하기 위해서 리팜핀 추가 시 와파린을 약 1주에 걸쳐서 단계적으로 약 2배 증량하고 리팜핀 중단 시 리팜핀 투여 전의 와파린 용량으로 감량하는 방법을 시도해 불 수 있겠고, 이를 향후 전향적 연구를 통해서 확인하는 것이 필요하다. 또한, 리팜핀을 추가하거나 중단할 때 합병증이 발생하지 않도록 항응고 상태를 자주 감시하는 것이 필요하리라 생각된다.