• Nutritional Sciences
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• 제3권1호
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• pp.11-17
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• 2000

This study was intended to examine whether dehydroepiandrosterone (DHEA) and dietary fat level or source could modulate glutathione utilizing detoxifying system activity and the cytosolic NADPH generation in rat liver. Male Sprague-Dawley rats were fed semipurifed diet containing either 2%(w/w) corn oil (low level of corn oil diet: 5 ca% of fat) 15% corn oil (high level of corn oil diet: 31 cal% of fat) or 13% sardine oil plus 2% corn oil(high level of fish oil diet: 31 cal% of fat) for 9 weeks. Half of the rats in each diet group were fed a diet supplemented with 0.2% DHEA (w/w). DHEA administration increased plasma total cholesterol level in low corn oil diet-fed rats. The high fish oil diet significantly decreased plasma total cholesterol level compared to the high corn oil diet. Plasma triglyceride level was not significantly changed by DHEA administration and dietary fat level and source. Fasting plasma glucose level was increased by DHEA administration and fish oil diet. Glucose 6-phosphate dehydrogenase activity in liver tissue was significantly increased by DHEA administration and high fat diet, especially fish oil diet. Malic enzyme activity in liver tissue was significantly increased by DHEA administration and high fat diet, especially fish oil diet. Malic enzyme activity in liver tissue was significantly increased by DHEA administration. DHEA suppressed the glutathione peroxidase, glutathione-dependent enzymes compared to the low corn oil diet, while fish oil diet elevated the activity of glutathione peroxidase and glutathione reductase compared to corn oil diet. These results suggest that DHEA administration and high level of corn oil diet may suppress the cellular detoxifying system activity through reduction of glutathione utilization, while the fish oil diet did not show these effects.

• Nutrition Research and Practice
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• 제2권2호
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• pp.80-84
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• 2008

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

• 대한한방내과학회지
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• 제37권6호
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• pp.1059-1068
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• 2016

Objectives: This study reports on the efficacy of treating patients with general weakness symptoms with Korean medicine. Methods: Two patients with general weakness symptoms were treated with Korean medical treatment modalities, including acupuncture, moxibustion, and herbal medicines. Blood tests, the visual analogue scale (VAS), and patients' complaints were used to assess the treatment effects. Results and Conclusions: dehydroepiandrosterone sulphate (DHEAS), DHEAS/cortisol index, VAS, and the patients' complaints improved after treatment. Korean medical treatment is effective in improving DHEAS and the DHEAS/cortisol index according to the improvements in the patients' conditions. However, more studies are required to validate its use with other patients.

• KSBB Journal
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• 제5권3호
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• pp.201-205
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• 1990

The characteristics of steroid acyl transferase were studied in the rat brain with (4-14C)-dehydroepiandrosterone(DHEA). The results could be summarized as followings: The enzyme system responsible for the biosynthesis was localized at the microsome fraction. The optimum pH of this enzyme was 4.6 When DHEA was utilized as substrate, $\Delta$5-pregnenolone was proved to be a competitive inhibitor. However testosterone was a noncompetitive inhibitor. The acylation at 3${\beta}$-hydroxyl group was favored when the hydrophilicity at Cl7 position increased. However, this acylation at C3 was very low when A ring was aromatic. The acylation at Cl7 hydroxyl group reguired an absolute 17${\beta}$-conformation.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.118-118
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• 2003

The influence of dietary supplementation with dehydroepiandrosterone-sulphate (DHEA-S) at 0.6% was investigated in male Syrian golden hamsters initiated by treatments with azoxymethane(AOM), and dihydroxy-di-n-propyl nitrosamine (DHPN), timed after transfer from a choline-deficient to a normal diet.(omitted)

• 대한약리학회지
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• 제26권1호
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• pp.67-76
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• 1990

웅성-마우스의 고환을 diethyl ether 마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사하여, 간 및 소장의 polyamine 함량과 소장의 diamine oxidase (DAO) 활성도에 미치는 그들의 영향을 검색하였다. 1. Hydrocortisone succinate 50 mg/kg (HC) 및 dehydroepiandrosterone 250 mg/kg (DHEA)에 의하여, 소장의 putrescine (PT)은 유의하게 증가되었으나, spermidine (SD) 및 spermine (SM)은 별 영향을 받지 않았고, 간의 SD은 다소 증가되고, SM은 다소 감소 되었으나, PT은 별 변동을 보이지 않았다. 2. Estradiol cypionate 5 mg/kg (E2)에 의하여, 간의 PT은 현저히 증가되었으나, 소장의 PT은 다소 증가되었고, 그외 소장 및 간의 SD와 SM의 변동은 보이지 않았다. Testosterone cypionate 5 mg/kg (TS)에 의하여는 간의 SD이 다소 감소되었을 뿐 별 변동이 없었다. 3. 소장의 DAO 활성도는 HC에 의하여 현저히 감소되었으나, E2 및 TS에 의하여는 유의하게 증가되었고, DHEA에 의하여는 별 영향을 받지않았다. 그러나 간의 monoamine oxidase 활성도는 HC, E2, DHEA, 및 TS에 의하여 영향을 받지 않았다. 4. Aminoguanidine 25 mg/kg로 소장의 DAO 활성도가 현저히 감소되었으나, 간 MAO 활성도는 영향을 받지 않았고, 소장의 PT 및 SD은 유의하게 증가되었으나, 간의 polyamine은 별 변동을 보이지 않았다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine 대사-특히 PT 함량의 변동이 각각 E2 및 HC에 의하여 특이적으로 조절되는 바, E2에 의한 간 PT 함량의 증가는 주로 생성촉진 작용에 연유되며, HC에 의한 소장 PT 함량의 증가는 주로 polyamine의 이화성 대사를 억제함에 기인될 수 있는 것으로 사료된다.

• Journal of Ginseng Research
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• 제44권6호
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• pp.790-798
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• 2020

Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.127-135
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• 1999

As part of a study on the effects of dexamethasone and dehydroepiandrosterone (DHEA) on the biological roles of astrocytes in brain injury, this study evaluated the effects of dexamethasone and DHEA on the responses of primary cultured rat cortical astrocytes to lipopolysaccharide (LPS) and antimycin A. Dexamethasone decreased spontaneous release of LDH from astrocytes, and the dexamethasone effect was inhibited by DHEA. However, the inhibitory effect of DHEA on the dexamethasone-induced decrease of LDH release was not shown in astrocytes treated with LPS, and antimycin A-induced LDH release was not affected by dexamethasone or DHEA. Unlike dexamethasone, DHEA increased MTT value of astrocytes and also attenuated the antimycin A-induced decrease of MTT value. Glutamine synthetase activity of astrocytes was not affected by DHEA or LPS but increased by dexamethasone, and the dexamethasone- dependent increase was attenuated by DHEA. However, antimycin A markedly decreased glutamine synthetase activity, and the antimycin A effect was not affected by dexamethasone or DHEA. Basal release of $[^3H]arachidonic$ acid from astrocytes was moderately increased by LPS and markedly by antimycin A. Dexamethasone inhibited the basal and LPS-dependent releases of $[^3H]arachidonic$ acid, but neither dexamethasone nor DHEA affected antimycin A-induced $[^3H]arachidonic$ acid release. Basal IL-6 release from astrocytes was not affected by dexamethasone or DHEA but markedly increased by LPS and antimycin A. LPS-induced IL-6 release was attenuated by dexamethasone but was little affected by DHEA, and antimycin A-induced IL-6 release was attenuated by DHEA as well as dexamethasone. At the concentration of dexamethasone and DHEA which does not affect basal NO release from astrocytes, they moderately inhibited LPS-induced NO release but little affected antimycin A-induced decrease of NO release. Taken together, these results suggest that dexamethasone and DHEA, in somewhat different manners, modulate the astrocyte reactivity in brain injuries inhibitorily.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.137-146
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• 1999

Interactions among dexamethasone, dehydroepiandrosterone (DHEA), lipopolysaccharide (LPS), and antimycin A on the glutamate uptake and the polyamine uptake were investigated in primary cultures of rat cerebral cortical astrocytes to examine the effects of dexamethasone and DHEA on the regulatory role of astrocytes in conditions of increased extracellular concentrations of glutamate or polyamines. 1. $[^3H]Glutamate$ uptake: LPS and antimycin A decreased $V_{max},$ but both drugs had little effect on $K_m.$ Dexamethasone also decreased basal $V_{max}$ without any significant effect on $K_m.$ And dexamethasone further decreased the antimycin A-induced decrease of $V_{max}.$ DHEA did not affect the kinetics of basal glutamate uptake and the change by LPS or antimycin A. 2. $[^{14}C]Putrescine$ uptake: LPS increased $V_{max},$ and antimycin A decreased $V_{max}.$ They showed little effect on $K_m.$ Dexamethasone decreased $V_{max}$ of basal uptake and further decreased the antimycin A-induced decrease of $V_{max},$ and also decreased $V_{max}$ to less than control in LPS-treated astrocytes. DHEA did not affect $K_m$ and the change of $V_{max}$ by LPS or antimycin A. 3. $[^{14}C]Spermine$ uptake: Antimycin A decreased $V_{max},$ and LPS might increase $V_{max}.\;K_m$ was little affected by the drugs. Dexamethasone decreased basal $V_{max}$ and might further decrease the antimycin A-induced decrease of $V_{max}.$ And dexamethasone also decreased $V_{max}$ to less than control in LPS-treated astrocytes. DHEA might increase basal $V_{max}$ and $V_{max}$ of LPS-treated astrocytes. 4. $V_{max}$ of glutamate uptake by astrocytes was increased by putrescine (1000 ${\mu}M$ & 2000 ${\mu}M$) and spermidine (200 ${\mu}M,$ 500 ${\mu}M$ & 2000 ${\mu}M$). Spermine, 200 ${\mu}M$ (and 100 ${\mu}M$), also increased $V_{max},$ but a higher dose of 2000 ${\mu}M$ decreased $V_{max}.\;K_m$ of glutamate uptake was not significantly changed by these polyamines, except that higher doses of spermine showed tendency to decrease $K_m$ of glutamate uptake. In astrocytes, dexamethasone inhibited the glutamate uptake and the polyamine uptake in normal or hypoxic conditions, and the polyamine uptake might be stimulated by LPS and DHEA. Polyamines could aid astrocytes to uptake glutamate.

• 대한약리학회지
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• 제27권1호
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• pp.81-88
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• 1991

웅성-마우스의 고환을 diethyl ether마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사한 다음 날의 오전 11-12 시에 뇌, 신장, 간장 및 소장의 polyamine을 검량하여 다음의 성적을 얻었다. 1. 고환절제-마우스(CM)에서, 소장 putrescine(PT)는 비고환절제-마우스(UCM)에 비하여 유의한 저하를 보였으나, 간 및 소장의 spermine(SM)은 오히려 유의하게 증가되었다. 2. Hydrocortisone 50 mg/kg는 UCM의 소장 PT는 현저히 증가시켰으나, CM의 뇌 PT 함량은 오히려 감소시켰다. 3. Estradiol 5 mg/kg는 UCM의 간 PT 함량을 현저히 증가시켰으며, CM에서는 간 PT 뿐만 아니라 신장의 전 polyamin 함량-증가와 아울러, 다소의 뇌 및 소장 PT-증가를 유도하였다. 4. Dehydroepiandrosterone 250 mg/kg(DHEA)와 testosterone 5 mg/kg(TS)는 UCM의 경우 신장 PT 함량만 유의하게 증가시켰으나, CM에서는 신장의 PT, spermidine(SD), 및 SM 모두를 더욱 현저히 증가시켰고, 아울러 DHEA는 간 SM의 감소를, TS는 뇌 SM의 유의한 증가를 유도하였다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine대사-특히 PT함량의 변동은 각각 E2 및 HC에 의하여 보다 특이적으로 조절되고, 신장의 polyamine 대사는 성steroid들에 의하여 다소 비특이적인 조절을 받는 것으로 생각되며, 고환절제-마우스에서 나타나는 HC에 의한 뇌의 전potyamine감소 및 성steroid들에 의한 신장의 전polyamine증가의 발현기전에 대한 연구가 있어야 할 것으로 사료된다.