• Archives of Pharmacal Research
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• 제21권2호
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• pp.120-127
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• 1998

Peroxisome proliferators induce hepatic peroxisome proliferation and hepatic tumors in rodents. These chemicals increase the expression of the peroxisomal $\beta$-oxidation pathway and the cytochrome P-450 4A family, which metabolizes lipids, including eicosanoids. Peroxisome proliferators transiently induce increased cell proliferation in vivo. However, peroxisome proliferators are weakly mitogenic and are not co-mitogenic with epidermal growth factor (EGF) in cultured hepatocytes. Earlier study found that the peroxisome proliferator ciprofibrate is cornitogenic with eicosanoids. In order to study possible mechanisms of the comitogenicity of peroxisome proliferator ciprofibrate and eicosanoids' we hypothesized that the co-mitogenicity may result from synergistic or additive increases of second messengers in mitogenic signal pathways. We therefore examined the effect of the peroxisome proliferator ciprofibrate, prostaglandin $F_2_{\alpha}$($PGF_2{\alpha}$) and the combination of ciprofibrate and $PGF_2{\alpha}$ with or without growth factors on the protein kinase C (PKC) activity, and inositol-1, 4, 5-triphosphate ($IP_{3-}$) and intracellular calcium ($[Ca^{2+}]_i$) concentrations in cultured rat hepatocytes. The combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased particulate PKC activity. The combination of ciprofibrate and $PGF_2{\alpha}$ also significantly increased EGF, transforming growth factor-$\alpha$ ($TGF_2{\alpha}$) and hepatic growth factor (HGF)-induced particulate PKC activity. The combination of ciprofibrate and $PGF_2_\alpha$greatly increased $[Ca^{2+}]_i$. However, the increases of PKC activity and $[Ca^{2+}]_i$ by ciprofibrate and $PGF_2{\alpha}$ alone were much smaller. Neither ciprofibrate or $PGF_2{\alpha}$ alone nor the combination of ciprofibrate and $PGF_2{\alpha}$ significantly increased the formation of $IP_3$. The combination of ciprofibrate and $PGF_2{\alpha}$, however, blocked the inhibitory effect of $TGF-{\beta}$ on particulate PKC activity and formation of $IP_3$ induced by EGF. These results show that co-mitogenicity of the peroxisome proliferator ciprofibrate and eicosanoids may result from the increase in particulate PKC activity and intracellular calcium concentration but not from the formation of $IP_3$.

• 한국식품영양과학회지
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• 제32권8호
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• pp.1364-1369
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• 2003

해조 올리고당 함유 음료, 해조 음료 소재 및 해조 추출물 제품을 식이성 고지혈증을 유발시킨 실험동물에 처리하여 체중 증가, 혈중 지질성분 및 간 지질성분의 변화에 미치는 영향을 시험하였다. 식이성 고지혈증을 유도한 흰쥐에 해조 음료 및 해조 추출물 제품을 7일간 투여한 결과, 현저하게 증가되던 체중이 감소하였으며, 체중 대 간장의 무게비도 식이성 고지혈증 유도군에 비해 감소하였다. 혈청중 중성 지질 및 인지질의 함량은 식이성 고지혈증의 유도로 증가되던 것이 해조 음료 및 해조 추출물 제품의 투여로 감소되었으며, 식이성 고지혈증에 의한 혈청중 total-, LDL-, HDL-cholesterol및 동맥경화지수도 해조올리고당의 투여로서 조절되었다. 고지혈증의 유도로 증가되었던 간장 중의 총지질은 해조 음료 및 다시마 추출 음료의 투여로 현저히 감소되었으며, 지질 성분중에서 cholesterol의 함량은 혈청에서와 마찬가지로 크게 감소하였고, 중성 지질(TG, triglyceride)의 함량은 해조 올리고당 음료 식이로 30%와 다시마 추출 음료 식이로 45% 정도가 감소하는 것을 확인하였다.

• 생명과학회지
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• 제15권4호
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• pp.613-618
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• 2005

치커리 수용성 추출물을 $2\%$ 및 $4\%$ 수준으로 첨가한 식이를 Sprague-Dawle계 흰쥐에 2주간 투여하여 중성지질 대사에 미치는 영향을 검토하였다. 혈청 중성지질 농도는 대조군에 비해 치커리 추출물 투여군에서 현저히 감소하였다. Apolipoprotein B-함유 lipoprotein의 합성 및 분비에 필수적인 간장 microsomal triglyceride transfer protein (MTP)활성도 치커리 투여군에서 현저히 감소하였다. 간 조직에서 중성지질 합성의 중요 조절효소로 알려진 phosphatidate phosphohydrolase (PAP) 활성은 각 실험군간에 큰 차이는 없었다. 또한 혈청 및 간 조직의 콜레스테롤, 인지질, 유리지방산 농도도 각 실험군간에 유의적인 차이는 없었다. 이상의 실험결과에서 치커리 수용성 추출물 $2\%$ 및 $4\%$ 첨가는 간 조직에서 혈중으로 분비하는데 중요한 역할을 하는 MTP활성의 감소가 혈청중성지질 농도의 감소에 영향을 미치는 중요한 요인으로 사료되었다.

• Journal of Nutrition and Health
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• 제26권5호
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• pp.532-546
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• 1993

This study was done to investigate the effects of different dietary oils on hepatic mitochondrial lipid compositon, adenine nucleotide translocase(AdNT) and ATPase activities in carcinogen treated rats. Sixty male Sprague-Dawley rats, weighing 50∼60g, were fed three different types of dietary oil, beef tallow(BT), corn oil(CO) and sardine oil(SO) at 15% by weight for 14 weeks. Three weeks after feeding rats were intraperitoneally injected with a single dose of diethylnitrosamine(200mg/Kg BW). After five weeks rate fed 0.02% acetylaminofluorene contating diet for 6 weeks, and after seven weeks 0.05% phenobarbital containing diet for 7 weeks. At 14th week, rats were sacrificed and hepatic mitochondrial lipid composition, AdNT and ATPase activities were determined. Percent liver weight per body weight was significantly by carcinogen treatment. Analysis of mitochondrial lipid composition showed that body cholesterol and phospholipid contents were not affected by dietary oils but significantly increased by carcinogen treatment. Individual phospholipid composition as well as phosphatidyl ethanolamine/phosphatidyl choline ratio were altered by either dietary oils or carcinogen treatment. Fatty acid composition was changed by dietary oils but not much by carcinogen treatment. AdNT activity was affected by dietary oils in only carcinogen treated groups. ATPase activity was affected by dietary oils in only carcinogen nontreated groups. These data indicate that both dietary oils and caricinogen treatment can change mitochondrial lipid composition and thereby change AdNT and ATPase activities. Particularly effects of carcinogen treatment on cholesterol/phopholipid ratio, phospholipid compositon and ATPase activity were different among dietary oil groups. Therefore it is suggested that different dietary oils can somewhat modulate the changes of mitochnodrial lipid composition and membrane bound enzyme activites during hepatocarcinogenesis.

• Journal of Nutrition and Health
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• 제33권5호
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• pp.497-501
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• 2000

We investigated the effect of tea fungus/kombucha(TF) beverage on serum and liver lipid metabolism in growing male rats. The rats(Sprague-Dawley) were divided into five groups; control(TF free water), 20 or 40% TF groups(20 or 40% TF in water) and 20 or 40% TFS groups(20 or 40% TF autoclaved in water) according to the level of TF supplementation. The rats were fed ad libitum each of the experimental beverage for 7 weeks. The body weight gain of all the TF and TFS groups were similar to that of the control group. The total lipid and triglyceride concentrations of serum in the 40% TF group were increased more than those in the control group, but those in the 20% TF and 20% TFS groups were similar to that of the control group. The total cholesterol, HDL-cholesterol concentrations, HDL-cholesterol / total cholesterol ratio and atherogenic index of serum in all the TF and TFS groups were similar to those of the control group. The LDL-cholesterol concentration of serum was significantly lower in the 20% TF group than that in the control group. The LDL-cholesterol concentration of serum was significantly lower in the 20% TF group than that in the control group, but those of the 40% TF, 20% TFS and 40% TFS groups were similar to that of the control group. The liver weights of all the TF and TFS groups were heavier than that of the control group. The concentrations of hepatic triglyceride in the 20% TF and 20% TFS groups were significantly decreased, compared with that in the control group. The concentrations of hepatic total cholesterol in all the TF and TFS groups were significantly more decreased than that in the control group. These results indicated that the liver weights of tea fungus/kombucha beverage feeding rats were increased, also the serum triglyceride and total cholesterol concentrations of 40% TF feeding rats were increased. but the serum LDL-cholesterol, hepatic triglyceride and cholesterol levels of 20% TF feeding rats were decreased.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1351-1360
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• 2023

Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrine-disrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroid-disrupting activity of EDC-derived metabolites and for proposing novel biotransformants.

• 생명과학회지
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• 제13권3호
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• pp.265-272
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• 2003

동충하초(C. militaris)의 균사체 액체배양액이 고지방 식이를 섭취한 성숙한 암쥐의 생리활성에 미치는 영향을 평가하고자, 생후 30주령의 흰쥐에 표준식이를 급여한 정상군, 표준식이에 15% 돈지와 1% 콜레스테롤을 첨가한 식이를 급여한 고지방군, 고지방 식이에 균사체 액체배양액을 각각 10%, 20% 및 30%씩 음료수에 혼합하여 급여한 군 등 5군으로 나누어 5주간 사육하였다. 실험동물의 체중증가, 식이효율, 및 간의 무게는 고지방군과 각 수준별 균사체 배양액군이 비슷한 수준을 보였으나 정상군 보다는 유의하게 증가되었다. 간의 총 지질 농도, 간과 혈청의 중성지질 농도 및 동맥경화지수는 고지방군에 비하여 20%와 30% 균사체 배양액군이 유의하게 감소시키는 효과가 나타났다. 혈청의 HDL-콜레스테롤 농도는 고지방군에 비하여 각 수준별 균사체 배양액군이 유의하게 증가시키는 효과가 나타났다. 분중 중성지질 배설량은 고지방군에 비하여 20%와 30% 균사체 배양액군이 유의하게 증가되었다. 간과 혈청의 총 콜레스테롤 농도, 혈청의 LDL-콜레스테롤 농도, 분의 콜레스테롤 배설량, 및 혈청의 GPT와 ALP의 활성은 고지방군과 각 수준별 균사체 배양액군이 비슷한 경향으로 나타났으나 정상군 보다는 유의하게 증가되었다. 총 콜레스테롤에 대한 HDL-콜레스테롤 비율은 정상군에 비하여 각 실험군이 유의하게 감소되었다. 혈당, 혈청의 총 단백질과 알부민 농도, 알부민/글로불린 비율, 신장과 대퇴골의 무게, 혈청의 COT와 ${\gamma}$-CTP의 활성은 정상군과 각 실험군이 비슷하여 정상 수준을 유지하였다. 이상의 결과로 보아 고지방 식이에 20% 및 30% 동충하초의 균사체 액체배양액 섭취가 간의 총 지질, 간과 혈청의 중성지질 농도 및 동맥경화지수를 낮추는 효과가 있고, HDL- 콜레스테롤 농도를 증가시키는 효과가 있는 것으로 나타났다.각된다.

• Environmental Analysis Health and Toxicology
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• 제7권1_2호
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• pp.45-51
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• 1992

This study was performed to investigate the effect of Angelicae gigantis Radix extract oil the hepatic detoxifying enzyme activities and lipids. Male sprague-dawley rats were administrated the extracts with benzo(a)pyrene, a hepatotoxic agent, inducing liver damages. Results obtained from this study were as follows: 1. The markedly increased enzyme activities (AST, ALT, LDH, ALP, ${\gamma}$-GTP, GSH-Px) in B(a)P induced groups tended to be decreased by the treatment of the Angelicae gigantis Radix extract. 2. Liver GSH content and lipid peroxide activity were decreased by the administration of the extracts. 3. It tended that the curative effects were better than the protective effects of the extracts.

• Journal of Nutrition and Health
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• 제34권5호
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• pp.493-498
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• 2001

To investigate the effects of Ixeris sonchifolia Hance diets on serum and hepatic lipid levles and enzyme activities in rats administered with ethanol chronically, Sprague-Dawley male rats were AIN-76 diet(control), control diet plus ethanol, control plus Ixeris sonchifolia Hance diet, or control plus Ixeris sonchifolia Hance diet plus ethanol for 30 days. Ixeris sonchifolia Hance diets significantly decreased the serum total cholesterol, triglyceride, LDL-cholesterol, and GOT levels that were increased due to the chronic ethanol administration. In addition, Ixeris sonchifolia Hance diets significantly decreased the liver triglyceride and total lipid levels that were increased due to the ethanol administration. The present findings, combined with previous data showing differences in the effects of cabbage diets having a high or a low level of GABA on the lipid levels and the serum Y-GPT activity of rats(Cha and OH[2000] J. Korean Soc. Food Sci. Nutr. 29, 500-505) raise the possibility that GABA in plants could have a nytraceutical role in the recovery of chronic alcohol-related diseases. (Korean J Nutrition 34(5) : 493∼498, 2001)

• Journal of Nutrition and Health
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• 제35권4호
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• pp.414-420
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• 2002

동충하초 (Cordyceps militaris)의 자실체와 균사체가 고지방 식이를 섭취한 성숙된 흰쥐의 영양 생리활성에 미치는 영향을 평가하고자, 생후 35주령의 흰쥐에 표준식이를 급여한 정상군, 표준식이에 15% 돈지를 첨가한 식이를 급여한 고지방군, 고지방 식이에 자실체 및 균사체를 각각 3%씩 첨가한 식이를 급여한 군 등 4군으로 나누어 5주간 사육하였다. 실험동물의 체중증가, 간의 무게 및 식이효율은 고지방군에 비하여 자실체군 및 균사체군이 유의하게 감소되어 정상군과 비슷한 수준으로 체중과 간의 무게를 정상으로 유지시켜 주는 효과가 나타났다. 식이섭취량은 고지방군과 동충하초군들이 비슷한 수준을 유지하였다. 신장, 췌장 및 심장의 무게는 정상군과 각 실험군이 비슷하였다. 간의 총 지질과 콜레스테롤 농도 및 간과 혈청의 중성지질 농도는 고지방군에 비하여 자실체군 및 균사체군이 유의하게 감소되었다. 혈청의 총 콜레스테롤 및 인지질 농도는 정상군에 비하여 각 실험군이 유의하게 증가되었다. 혈청의 HDL-콜레스테롤 농도는 정상군에 비하여 자실체군 및 균사체군이 유의하게 증가되었다. 고지방군에 비하여 자실체군의 총 콜레스테롤에 대한 HDL-콜레스테롤 비율은 유의하게 증가되었고, 동맥경화지수는 감소되었다. 혈청의 총 단백질 농도는 정상군에 비하여 고지방군 및 균사체군이 유의하게 증가되었다. 혈청의 알부민, 혈당 및 혈색소 농도는 정상군과 각 실험군이 비슷하여 정상 수준을 유지하였다. 혈청의 glutamic pyruvic transaminase, glutamic oxaloacetic transaminase 및 ${\gamma}$-glutamyltr-anspeptidase의 활성은 정상군과 각 실험군이 유사한 경향을 보였다. Lactic dehydrogenase 활성은 고지방군에 비하여 자실체군 및 균사체군은 유의하게 증가되어 정상군과 비슷하였다. Alkaline phosphatase 활성은 정상군에 비하여 각 실험군이 유의하게 감소되었다. 이상의 결과로 보아 고지방 식이에 3%동충하초의 자실체와 균사체 섭취에 의한 체중과 간의 무게가 정상수준을 유지하였고, 간의 총 지질과 콜레스테롤 농도 및 간과 혈청의 중성지질 농도를 낮추는 효과가 있는 것으로 나타났다.